2019 TDDW Abstract Book

2019

Theme: Challenges and Opportunities in Digestive Diseases

September 28th (Sat) ~ 29th (Sun), 2019 Kaohsiung Exhibition Center 高雄展覽館

2019 Taiwan Digestive Disease Week, TDDW Abstract Book INDEX Chairman’s Lecture ...............................................................................................1 Keynote Lecture (II) (III)

Battle Against Viral Hepatitis and Liver Cancer in Taiwan ....................................2 Remaining Challenges of HCV in the Post-Daa Era .............................................3

Special Lecture (I) (II) (III)

Third Space Endoscopy ........................................................................................4 Oral Microbiome and Cancer ................................................................................5 Problem of Current Guidelines and Suggestion of Optimal Treatment in Gallbladder Cancer ...............................................................................................6 (IV) Emerging Applications in Gut Microbiota ..............................................................7 (V) Advances in Endoscopic Resection of Colorectal Neoplasia ...............................8 (VI) High Resolution Esophageal Manometry: Practicalities and Added Value of Impedance ............................................................................................................9 (VII) HBsAg Loss in Chronic Hepatitis B Patients.......................................................10 (VIII) Harnessing the Gut Microbiome to Improve Metabolic Health and Fatty Liver ...11

Symposium (I) (II) (III) (IV) (V) (VI) (VII) (VIII) (IX) (X) (XI) (XII) (XIII) (XIV)

Immunotherapy in Hepatogastroenterological Cancers ......................................12 AI Aspect of Liver Disease ..................................................................................15 Neurogastroenterology and FGID Management .................................................19 Gastrointestinal Polyposis Syndrome .................................................................22 Biliopancreatic Drainage .....................................................................................26 Pancreatic Cancer – Treatment Approaches and Trends ...................................30 The Clinical Implication of Probiotics ..................................................................32 GEST-KASID Joint Symposium ..........................................................................36 New Frontier of Digestive Endoscopy Technique ...............................................42 HCC Diagnosis and Therapies: Update and Real-World Experiences ...............45 Sarcopenia and Liver Disease ............................................................................49 Gut Microbiome and Human Diseases: Current Development ...........................53 Recent Progress in Understanding and Management of GIST...........................57 Update of Neuroendocrine Tumors .....................................................................61

The 3rd Joint Session Between TDDW – JDDW – KDDW (I) (II) (III) (IV)

Long-term Effects of Helicobacter pylori Eradication in the Asia-Pacific Region: Other Benefits or Concerns? .................................................................63 Autoimmune Pancreatitis: Current Diagnosis & Management in the Asia-Pacific Region .............................................................................................69 Post-colonoscopy Colorectal Cancer: From Practice to Screening Program Perspectives.........................................................................................75 Optimization of Direct Anti-viral Agent Treatment for HCV: Current Status in the Asia-Pacific Region ...........................................................84

Young Investigator Award (YIA) ..................................................................94 Free Paper (I) (II) (III) (IV) (V) (VI)

HCV ..................................................................................................................102 LGI ....................................................................................................................107 HBV...................................................................................................................112 Pancreas / Biliary ..............................................................................................117 Cirrhosis & HCC................................................................................................122 UGI....................................................................................................................127

Poster Liver ............................................................................................................................133 GI ................................................................................................................................235

2019 TDDW

Chairman’s Lecture THE LAST MILE IN THE FIGHT AGAINST HCV Ming-Lung Yu Hepatitis Research Center, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Since the discovery of hepatitis C virus (HCV) in 1989, the fight against HCV evolved slowly in the first two decades. The mainstream is interferon-based therapy, from genotype-guided therapy to response-guided therapy. Not until the IFN-free first directly acting antivirals (DAA) approved in 2013, the revolution of DAA in HCV treatment is moving promptly from to resourceguided strategies to IFN-free strategies with genotype-specific algorithm to pan-genotypic algorithm, which are currently standard-of-care.

With the current secondary generation DAA regimens, we are able to cure > 98% of HCV patients. Based on such high SVR rate, broad indications and safety profile, we are currently on the last mile to the elimination of the virus.

However, there remain hurdles on the last mile in the fight against HCV.

Child-Pugh class B or C decompensated liver cirrhosis will continue progress to hepatic failure after SVR achieved, especially for those with MLED score > 20.

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HCC risk remains, especially among patients with advanced fibrosis at baseline, old age, diabetes and persistently high levels of alfafetoprotein or liver enzymes. Recent studies demonstrated that HCV-induced epigenetic changes associated with liver cancer risk persist after SVR, suggesting HCC remains an unmet need after SVR.

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Extrahepatic manifestations, although decreased in prevalence after SVR, will persist among substantial proportion of HCV patients after SVR, and need life-long monitoring/care. We observed that rebound of lipid profiles are not uncommon after SVR achieved, especially among those of older age or with history of smoking. Post-SVR LDL surge (>40%) increased significantly the risk of major cardiovascular events.

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Chronic HCV infection increases the risk of T2DM. By gene microarray of liver tissues and HCV cell models, we found a key hepatic regulator of glucose homeostasis downregulated by HCV infection. Restoration of the key regulator could normalize the glucose homeostasis in cell experiments and animal models, indicating a potential new target of glucose control for T2DM.

Last mile to eliminate the virus: 1)

2)

Barriers to HCV elimination: Low disease awareness and accessibility in the care cascades of HCV treatment are the major hurdle on the way to HCV elimination. Finally, lack of HCV vaccine, HCV would never be completely erased.

The DAA failed patient number, although very few, will accumulate year by year. The multiple drug resistance HCV strains will be very difficult-to-cure population in the near future.

Hurdles to reverse HCV-related morbidity/ mortality: 3)

Substantial number of patients who have

Understanding the mechanisms of “point of no return” in HCV-related morbidity and mortality will help us to defeat the “hepatitis C” properly.

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2019 TDDW

Keynote Lecture (II) BATTLE AGAINST VIRAL HEPATITIS AND LIVER CANCER IN TAIWAN Chien-Jen Chen Genomics Research Center, Academia Sinica, Taipei, Taiwan Liver cancer was the leading cause of cancer death for men and the second leading cancer death for women in last three decades in Taiwan. Epidemiological studies have identified major etiological factors for liver cancer in Taiwan including hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol, aflatoxin, and obesity. Chronic infection of HBV and HCV is the most important causes of hepatocellular carcinoma (HCC) in Taiwan. Many risk factors may be combined to derive the risk calculators for the prediction of long-term risk of HCC in patients with chronic infection of HBV or HCV. They are important for the triage of patients who need intensive liver surveillance and/or antiviral therapy, and for the efficacy evaluation of clinical managements of chronic hepatitis B (CHB) or chronic hepatitis C (CHC). Risk calculators for prediction of HCC in CHB and CHC patients have been derived and validated in the Southeast and East Asia.

The national hepatitis B immunization program in Taiwan was launched in 1984 with a coverage greater than 90% of newborns.

A significant reduction in incidence of HCC among immunized birth cohorts has been welldocumented since 1997. In comparison with unimmunized birth cohorts born in 1976-1980 as the referent group, the age-sex-adjusted relative risk of HCC was 0.68, 0.33, 0.29, 0.14 for immunized birth cohorts born in 1981-1985,

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1986-1990, 1991-1995, and 1996-2000. The protective eect may last for three decades after hepatitis B immunization at birth. The risk factors for developing HCC among 3.8 million immunized newborns included maternal serostatus of HBV surface antigen (HBsAg) and e antigen (HBeAg) as well as incomplete immunization.

Many clinical trials and observational studies have documented a significant decline in HCC risk among CHB and CHC patients treated with anti-virals. The national chronic viral hepatitis therapy program in Taiwan was launched in 2003.

The mortality and incidence of HCC for antiviraltreated groups have significantly declined in recent two decades in Taiwan. In comparison with the period of 2000-2003 before the launch of national therapy program as the referent group, the age-sex-adjusted relative risk of HCC mortality (incidence) was 0.95 (0.98), 0.76 (0.86), 0.64 (0.75), 0.56 (0.65) for the periods in 20042007, 2008-2011, 2012-2015, and 2016-2017.

Age-period-cohort analyses of HCC incidence have further confirmed a significant decline in HCC incidence in birth cohorts born after 1980 and in calendar periods after 2000, implying the benefit of the national hepatitis B immunization program and chronic viral hepatitis therapy program. It is expected to achieve the goals of viral hepatitis elimination in Taiwan before 2030 as proposed by World Health Organization.

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Keynote Lecture (III) REMAINING CHALLENGES OF HCV IN THE POST-DAA ERA Raymond Chung Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA The introduction of all oral, pangenotypic, well tolerated direct acting antiviral agents (DAA) against hepatitis C virus has sparked a profound treatment revolution. We have seen extraordinary rates of real world cure, and corresponding improvements in hepatic and even extrahepatic outcomes, including reduced rates of progression to cirrhosis, liver failure and hepatocellular cancer, but also improved rates of all-cause mortality, including improvements in cardiovascular disease, renal disease and rates of certain extrahepatic malignancies. There remain challenges in the post DAA era, including (1) implementation of widespread access to DAA therapy worldwide, which will require concerted governmental and stakeholder engagement to accomplish the WHO

targets for elimination; (2) the development of a broadly reactive vaccine, which will be required for eradication of HCV; (3) the residual persistent risk of HCC among patients with advanced fibrosis, a reflection of several pathogenetic factors, including genetic and epigenetic alterations; (4) the (rare) occurrence of DAA-resistant HCV, including in uncommon genotypes/subtypes as well as in patients with HCC. Finally, the challenge of donor organ shortages for persons awaiting organ transplantation has given rise to (5) novel opportunities for use of DAAs to enable successful transplantation of HCV infected donor organs. These challenges and opportunities will be considered in greater detail.

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2019 TDDW

Special Lecture (I) THIRD SPACE ENDOSCOPY Haruhiro Inoue Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan Fist space is GI natural lumen. Second space is peritoneal cavity. Third space is an intentionally created cavity in submucosal layer by therapeutic endoscopy. In 2008 world ďŹ rst case of POEM was successfully done. Now POEM is well accepted in the whole world. With its successful launch other applications of submucosal endoscopy were reported. Gastric POEM was applied to gastric paresis. POET (STER) is an application of POEM technique to resection of submucosal tumor. All details of procedure and outcome will

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be discussed.

References: 1.

Inoue H, Minami H, Kobayashi Y et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010;42:265-71.

2.

Khashab MA, Pasricha PJ. Conquering the third space: challenges and opportunities for diagnostic and therapeutic endoscopy.

Gastrointest Endosc. 2013;77:146-8.

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Special Lecture (II) ORAL MICROBIOME AND CANCER Christian Abnet Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA The human microbiome is postulated to play multiple roles in human health and disease. Most current studies of the human microbiome and cancer risk have used stool as a proxy for the microbial population of the gut lumen. But the oral cavity harbors dierent bacterial communities that are uncorrelated with stool microbiome communities in healthy subjects. The oral microbiome appears to play distinct physiological roles relevant to cancer risk including its role in periodontal disease and the attendant inflammation, metabolism of nitrate and other dietary components, as well as playing a role in the metabolism of other carcinogenic exposures such as ethanol. Furthermore, oral cavity-derived bacteria are continually seeding the stomach and may influence immune response. Poor oral health and hygiene have been associated with risk of esophageal, gastric, pancreatic, and head and neck cancers and these associations are probably mechanistically dependent on the oral

microbiome. Much of the current literature has been generated from cross-sectional case-control studies and reported differences are difficult to separate from reverse causation. That is, the oral microbiome of subjects at the time of cancer diagnosis probably reflects recent changes due to illness rather than the oral communities that existed during the time at which tumors were developing. Many large cohort studies banked oral wash specimens as a source of human DNA, but these oer an opportunity to use these saliva banks for microbiome studies. Several recent papers report results from prospective cohort studies, which better test the association between oral bacteria and risk of cancer in humans. Here I present an overview of measuring the oral microbiome in free-living subjects and a largescale study of the oral microbiome and cancer risk using three prospective cohort studies from the United States that collectively banked oral wash specimens from over 100,000 subjects.

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2019 TDDW

Special Lecture (III) PROBLEM OF CURRENT GUIDELINES AND SUGGESTION OF OPTIMAL TREATMENT IN GALLBLADDER CANCER Jin-Young Jang Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea In spite of different epidemiology of biliary tract cancer (higher incidence in Asia), most of countries are using NCCN guidelines based on SEER data. The optimal surgical extent for especially early (T1, T2) gallbladder cancer (GBC) remains controversial. Simple cholecystectomy is routinely performed for T1 GBC in practice, but most of guidelines recommend extended cholecystectomy for T1b GBC including NCCN. However, evidence regarding the optimal surgical extent for T1 and T2 GBC is lacking. Moreover, current guidelines are based on national database such as SEER, NCDB which lack of information on disease free survival, depth of invasion and side of tumor location (new category in AJCC 8th staging). Especially early GB cancer needs more sophisticated specimen handling including mapping. In this situation, collaboration research is mandatory to get a final conclusion in this issue. Several years ago, distinguished researchers from GB cancer prevalent area such

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as Chile, Korea, Japan gathered at Santiago with some USA pathologist and epidemiologists. At that time, we discussed the several issues in GB cancer especially on early lesions (T1 and T2) including epidemiology, pathologic diagnosis, and surgical issues. To solve this confusing situation, we decided to gather the data on GB cancer from the hospitals which are supported by established pathologists, specialized biliary surgeons and high quality data including follow up. I could gather 1,469 cases from 14 institutes in four countries (Korea, Japan, Chile and USA). We gathered T1b 272, and T2 1,197. We analyzed the survival and recurrence data according to types of surgery.

In this lecture, we will show the clinical outcome on GB cancer according to the type of surgery. Through this international multicenter study we could get an optimal treatment on the early GB cancer by depth of invasion. And I would like to touch other controversial surgical issues in GB cancer.

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Special Lecture (IV) EMERGING APPLICATIONS IN GUT MICROBIOTA Sunny H. Wong Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Colorectal cancer is one of the most common cancers in the world. Metagenomic studies have revealed microbiota changes in patients with colorectal cancer, whereas functional studies have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum, Peptostreptococcus anaerobius and certain strains of Escherichia coli and Bacteroides fragilis. These results give

new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as biomarker for diseases screening or diagnosis, or its modulation for disease prevention or treatment. In this lecture, I will provide an overview of the gut microbiota in colorectal neoplasia, and discuss the potential of utilizing the microbiota for clinical applications.

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2019 TDDW

Special Lecture (V) ADVANCES IN ENDOSCOPIC RESECTION OF COLORECTAL NEOPLASIA Andrew Wang Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA Colorectal cancer is a significant clinical problem worldwide. Despite the development of advanced endoscopic resection techniques for colorectal neoplasia, surgical resection of nonmalignant colorectal polyps continues to be commonly performed exposing many patients to unnecessary medical risks. Improved education regarding the identification of colorectal polyps that can be removed endoscopically is necessary.

Additionally, gastrointestinal endoscopists who are trained in variations of endoscopic mucosal resection (EMR), endoscopic sumbuosal dissection (ESD), and endoscopic full thickness resection (EFTR) techniques are needed to treat patients with premalignant colorectal neoplasia or

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early colorectal cancer.

This lecture will discuss the assessment of colorectal lesion morphology and use of advanced optical imaging to accurately diagnose dysplastic polyps and invasive colorectal cancers, which is essential for proper treatment selection. Advanced endoscopic resection techniques and the data supporting their use for colorectal neoplasia will be a major focus of this presentation. Of particular focus will be advancements in EMR including underwater EMR and cold EMR, in addition to how and for which lesions ESD or EFTR might be used to treat dysplastic polyps and early colorectal malignancies.

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Special Lecture (VI) HIGH RESOLUTION ESOPHAGEAL MANOMETRY: PRACTICALITIES AND ADDED VALUE OF IMPEDANCE Taher Omari College of Medicine and Public Health, Flinders University, Adelaide, Australia Esophageal dysphagia is a common symptom encountered in gastroenterology.

Following endoscopy and exclusion of an organic process such as, oesophageal cancer, peptic strictures and eosinophilic esophagitis, high-resolution manometry (HRM) can be used to characterize esophageal dysmotility as a mechanism of symptom generation. The Chicago classification, based on esophageal pressure topography, has become the gold-standard algorithm for manometric diagnosis. HRM is

also recommended for the assessment of reflux patients prior to anti-reflux surgery. Esophageal impedance topography is a readily available adjunct technology, now with an evolving set of associated analysis methods and metrics based on the integration of pressure and impedance.

These may provide additional information to support diagnosis of dysmotility or to detect subtle pressure abnormalities during bolus transport that may explain pathophysiology and symptoms.

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2019 TDDW

Special Lecture (VII) HBSAG LOSS IN CHRONIC HEPATITIS B PATIENTS Mindie H. Nguyen Division of Gastroenterology and Hepatology and Liver Transplant, Stanford University Medical Center, California, USA Despite the use of a preventive vaccine for several decades as well as effective and welltolerated viral suppressive medications since 1998, there are still approximately 250 million people or more infected with the virus that causes hepatitis B (HBV) worldwide. Seroclearance of a qualitative test for HBsAg (i.e. loss of HBsAg, which equals to <0.05 IU/mL in serum) with or without the appearance of antibodies [anti-HBs] is regarded as a functional cure. Protective immunity is acknowledged when there is an anti-HBs level greater than 10 IU/mL. HBsAg levels and the source of HBsAg production change over the different phases of chronic hepatitis B (CHB). HBsAg concentrations are high during the immune tolerant phase, while they are low in the inactive phase. The source of HBsAg production also changes from predominantly cccDNA transcription in the young HBeAg-positive patient to HBV integrants in the older HBeAg- negative patient.

The cure of CHB is not possible at this point with current antiviral drugs. Thus, the current therapeutic goal is to achieve functional cure, the seroclearance of HBsAg. It is an important marker of sustained immune control of HBV infection and

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is associated with improved clinical outcomes with lower risk of decompensated cirrhosis, HCC incidence, and liver-related death.

The reported rates of HBsAg seroclearance have been rare and variable. Previous cohort studies demonstrated that the annual HBsAg seroclearance rate ranged from 0.12% to 2.38%.

Recent meta-analytic data from 34 studies (42,588 patients, 303,754 person-years, 3,194 HBsAg seroclearance events) reported a pooled annual HBsAg seroclearance rate of only 1.02% (95% CI: 0.80-1.26), and the long-term rates did not follow a linear pattern with 5-, 10-, and 15year cumulative incidence rates of 4.03% (95% CI: 2.49-5.93), 8.16% (95% CI: 5.24-11.72), and 17.99% (95% CI: 6.18-23.24), respectively.

Negative HBeAg status, low HBV DNA, and low quantitative HBsAg level at baseline were associated with a higher seroclearance rate, but not antiviral treatment (with mostly oral nucleoside analogs). However, treated patients likely had characteristics associated with lower HBsAg seroclearance rates; therefore, additional studies with individual patient level data are needed to better characterize and identify factors associated with HBsAg seroclearance rates in CHB patients undergoing oral nucleos(t)ides.

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Special Lecture (VIII) HARNESSING THE GUT MICROBIOME TO IMPROVE METABOLIC HEALTH AND FATTY LIVER Tibor Krisko Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USA Interactions between the gut microbiota and the host are major determinants of health and disease. While alterations in the composition and function of the gut microbiome have been identiďŹ ed in persons with obesity, type-2 diabetes and non-alcoholic fatty liver disease (NAFLD), we do not yet have a mechanistic understanding of how microbes or microbial-derived products contribute to disease pathogenesis. The gut microbiome has been suggested to influence energy balance through the recruitment of brown and beige adipocytes, primary mediators of the adaptive thermogenic response.

Utilizing complementary mouse models of gut microbiome depletion, we have demonstrated that gut microbiota are not required for coldor diet-induced recruitment or activation of brown or beige adipocytes. Neither ablation

of the gut microbiome, nor the substantial microbial perturbations induced by cold ambient temperatures, affect energy expenditure during cold exposure or high fat diet feeding.

Notwithstanding, we demonstrated a critical role for the gut microbiome in maintaining euglycemia by regulating hepatic amino acid metabolism to optimize TCA cycle fluxes in support of hepatic gluconeogenesis. Taken together, these results distinguish the dispensability of the gut microbiome in the regulation of energy expenditure from its critical contribution to the maintenance of host glucose homeostasis.

These findings suggest that harnessing the gut microbiome may be a viable therapeutic strategy to improve host glucose metabolism and alleviate NAFLD.

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2019 TDDW

Symposium (I) IMMUNOTHERAPY IN HEPATOGASTROENTEROLOGICAL CANCERS

OVERVIEW OF IMMUNOTHERAPY Chiun Hsu Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan Development of immunotherapy is one of the hottest research fields in oncology therapeutics. The greatest progress is seen in immune checkpoint inhibitor (ICI) therapy, which has proven anti-cancer efficacy in more than 10 types of solid cancers. Other immunotherapeutic approaches, such as cell therapy or vaccine therapy, are still struggling for their potential niche in the treatment of solid cancers.

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The advance in ICI therapy also challenges our traditional thinking in many aspects of oncology new drug development, including clinical trial design/ interpretation and exploration of predictive biomarkers. In this presentation examples from successful and not-so-successful clinical trials of ICI therapy for different cancer types will be discussed to illustrate these issues.

2019 TDDW

Symposium (I) IMMUNOTHERAPY IN HEPATOGASTROENTEROLOGICAL CANCERS

RISK AND MANAGEMENT OF IRAES AMONG PATIENTS RECEIVING IMMUNOTHERAPY Wen-Cheng Chang Division of Hematology-Oncology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Immunotherapy has become a great means of cancer treatment, and its anticancer activities have been validated in a lot more types of cancer. However, the emerging immunotherapy modalities are associated with severe toxicities, and many healthcare providers do not have a comprehensive understanding of immunotherapy.

Cancer therapy employs a multidisciplinary approach that engages experts from surgery, internal medicine, radiation oncology and other related disciplines; close collaboration of multidisciplinary teams can lead to correct diagnosis, staging and treatment strategies and subsequently the most beneďŹ t to the patients.

Management of immune-related adverse events (irAEs), including nausea, vomiting, mucositis, loss of appetite, fever, infection, and hepatic and renal impairment, was important and needed the assistance from nursing staff, dietician and physiotherapist to provide appropriate care. These irAEs are different in terms of profile and management. Chang Gung Memorial Hospital established a multidisciplinary healthcare team in 2015 in order to optimize the treatment outcome through knowledge learning, continuous education, and collective experience of toxicities management from a multidisciplinary approach. In the out-patient setting, an hour of patient education through published materials is delivered in a special clinic to encourage patients and their family to be aware of the potential

toxicities, management procedures, preliminary judgement about the symptoms and emergent hospital visit system. This healthcare system enables patients to receive early detection upon initial onset of irAEs followed by close monitoring and timely management.

The multidisciplinary team consists of professionals with diďŹ&#x20AC;erent specialties in oncology, pharmacology and nursing, supplemented by those from dermatology, gastroenterology, pulmonary medicine, endocrinology disciplines and paramedical units to assist diagnosis, such as diagnostic radiology, nuclear medicine pathology, and emergency medicine. Doctors from the emergency medicine are also included in order to deliver timely management as soon as the patients arrive at emergency room with suspected irAEs. This system has an immediate response to treat irAEs. Tumor board discussions are held every other week to review the diagnosis and management of irAEs, and to discuss with the treating physician and medical team the process and outcome. All participants have deepened their knowledge of immunotherapy drugs and irAEs, and their understanding of the principles of irAEs management.

In general, irAEs occur mostly within a few weeks to 3 months after initiation of immunotherapy. However, a small portion of irAEs has been documented as long as 1 year after discontinuation of treatment. Before

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2019 TDDW initiation of immunotherapy, patients should be assessed in terms of susceptibility to developing irAEs. This includes a work-up consisting of personal or family medical history, general physical condition, baseline laboratory tests and radiological examinations. Patients with a history of autoimmune diseases are at high risk of developing irAEs. Patients who have received multiple immune checkpoint blockade also face an increased risk that goes with immunotherapy.

Before starting the treatment, patients should be fully informed of all pertinent risks of potential irAEs. Once irAEs have developed, especially the most severe types, it is suggested to discontinue treatment and introduce timely intervention with immunosuppressive agents to overcome the toxicities, followed by careful tapering of immunosuppression. In previous years, we manage irAEs in accordance with package inserts and label instructions from the pharmaceutical manufacturers and guidelines published in Europe. Generally, for grade 1 irAEs, observation is preferred and supportive care is given as appropriate without interruption of immunotherapy; for grade 2 irAEs, the main principle is similar with the exception of initiation of steroids when needed, in which case the immunotherapy can be resumed after recovery; for grade 3 or 4 irAEs, it is recommended the steroid treatment be started and maintained for no less than 4 weeks

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and immunotherapy be discontinued. The role of tissue biopsy in the diagnosis of immunotherapy related toxicity has not yet been established in clinical practice. Some recommendations suggest tissue biopsy in higher grade toxicity where there is diagnostic uncertainty or doubt about the etiology of the complication, and judgement or management would be altered by the outcome of the biopsy procedure. When biopsy is carried out in a context of this sort, the reporting pathologist must be apprised of the specific reasons for the biopsy procedure. Recently, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network® (NCCN®) have a joint collaboration to publish practical clinical guidance on the management of irAEs. As we started irAE multidisciplinary team in 2015, the rules for management of toxicities was following the European guidelines along with modifications based on our clinical practice experience from the last 4 years.

For the best results of immunotherapy, it is fundamentally critical to deepen the understanding of immunotherapy properties, toxicities management, and especially the importance of multidisciplinary team for treatment delivery, a novel style for patients and relative’s education, complete baseline examinations, close monitoring during treatment, timely identification and proper intervention upon onset of toxicities.

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Symposium (II) AI ASPECT OF LIVER DISEASE

AI AND LIVER DISEASES Raymond Chung Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Artificial intelligence refers to the ability of machines to process large quantities of data and approximate human cognition in their analysis.

AI does this through the use of machine learning algorithms. These algorithms can recognize patterns in behavior and create their own logic.

AI algorithms, through repeated testing, reduce the margin of error. Deep learning refers to machine learning employing multilayered neural networks algorithms. AI programs have been most productively developed and applied to practices such as diagnosis, treatment protocol development, drug development, personalized medicine, and prognostic determinations. The best examples of the use of AI have come from two major domains, including analysis of imaging and pathologic data, and analysis of electronic health record data. While numerous studies have analyzed deep image acquisition from endoscopic images to assist with lesion detection in gastroenterology, this task has been applied principally In the liver to the detection and identification of focal liver lesions, as well as their classification. An increasing number of studies are also investigating the ability of deep learning to make stronger correlations between

contrast-enhanced CT images and histologic liver fibrosis, sometimes with impressive accuracy.

Work is also underway to use neural networks to perform segmentation of the liver in planning for surgery, as well as providing prognostic data regarding response to locoregional treatments for HCC. In the area of pathology, convolutional neural networks are being used to train on features of NAFLD and NASH in the hopes of standardizing the approach to the diagnosis and staging of NASH. In the realm of the EHR, use of natural language processing can be exploited to enhance the detection of NAFLD by recognizing key associated risk factors and markers even in the absence of diagnosis codes. Use of machine learning approaches has led to development of models that predict NASH advanced fibrosis clinical deterioration using only noninvasive variables as accurately as models including invasively obtained data. Similarly, AI approaches are being applied to large databases such as UNOS to predict transplant waitlist removals.

While it is likely that AI approaches will not replace clinical judgment and obviate the primacy of clinicians, we can anticipate that AI will augment the eďŹ&#x20AC;ectiveness of these clinicians.

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Symposium (II) AI ASPECT OF LIVER DISEASE

MACHINE LEARNING FOR LIVER PATHOLOGY Tung-Hung Su Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan With the advancement of scanning technique for whole slide imaging, digital pathology become a new paradigm for pathological diagnosis. The rapid accumulation of digital histopathological images increase the demand for computer-aided diagnosis using machine learning algorithms.

Both of the supervised, or unsupervised learning may be applied in certain clinical or research scenarios. The machine learning application in digital pathology includes computer-assisted diagnosis, content based image retrieval, and discovery new clinicopathological relationships.

However, these computational technology also

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faces several challenges regarding to image size, tissue annotation, problems of scanning and image processing.

The new multiplexed histopathological imaging platform enables high-dimensional single-cell analysis. However, the huge dataset challenges the data scientists to analyze multiple parameters of single cells with spatial information in a complicated microenvironment. These new pathological technologies open another new ďŹ eld of research and might revolutionize the current pathological diagnosis.

2019 TDDW

Symposium (II) AI ASPECT OF LIVER DISEASE

ROLES OF AI IN LIVER DISEASE Chih-Horng Wu Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan Artificial intelligence is developing for a long time since 1950’s until dramatic growing since 2010’s. Any technique which enables computers to mimic human behavior can be regarded as artificial intelligence (AI). Alan Mathison Turing was an English mathematican and is considered to be the father of computer science and AI. Machine learning (ML) is a subset of AI technique which uses statistic methods to enable machine.

The algorithms of ML include decision trees, support vector machines, regression, and Bayes classification etc. Deep learning (DL) is a subset of ML technique which uses multi-layer neural networks. The input layer, multiple hidden layers and output layer compose the structure of DL. The traditional machine learning requires a small to medium datasets, a low-end machine and feature extraction. We can interpret the output image by the determining features. In contrast, the deep learning needs a big dataset,

a powerful GPU. In is very difficult to interpret the output due to multiple hidden layers in DL. ImageNet is a labeling image database for ML. The team of professor Li Fei-Fei in Stanford University maintained the database and held the ImageNet Large Scale Visual Recognition Challenge (ILSVRC) from 2010 to 2017. Since 2012, the convolutional neural networks beat the feature engineering.

There are 14 FDA approvals for AI-based algorithms in medicine until May/2019. Most of them focus on neurologic or cardiothoracic imaging. Only one has liver cancer diagnosis on CT and MRI. Therefore, there is great potential to utilize DL in the field of liver disease. Detection, segmentation, interpretation and inference are the possible roles of AI in liver disease. We hope all these efforts can help doctors to provide better care to patients.

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2019 TDDW

Symposium (II) AI ASPECT OF LIVER DISEASE

ROLES OF AI IN LIVER DISEASE Jyh-Shing Jang Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan This talk introduce the common practice of machine learning for medical/healthcare data analytics, including practical concerns and difficulty in data cleaning and normalization. We

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shall use a case of fatty liver detection to illustrate how these techniques can help the creation of a better model for better prediction.

2019 TDDW

Symposium (III) NEUROGASTROENTEROLOGY AND FGID MANAGEMENT

HIGH RESOLUTION PHARYNGEAL MANOMETRY: THE BASICS AND CLINICAL IMPLICATION Taher Omari College of Medicine and Public Health, Flinders University, Adelaide, Australia High-resolution manometry is now widely utilized in gastroenterology for diagnostic, clinical and research applications. Recently, it is also finding new and important applications in speech pathology. Pharyngeal swallowing involves different motor responses that all require sensory feedback and coordination of the central nervous system. When swallowing muscles contract and relax, the intraluminal pressures and luminal diameters in the pharynx change. ManometryImpedance can directly measure these changes.

Manometry records the pressures generated during food bolus transport (peristalsis) and

these pressures can be displayed as colour topographical plots. Simultaneously, intraluminal impedance determines bolus movement and changes in luminal diameter. Analysis of these responses to different volumes and consistencies is a paradigm to study the sensory feedback from oral and pharyngeal regions. The Swallow-RiskIndex is a global outcome measure, a score of 15+ is diagnostic for aspiration risk, providing a simple to use/apply/interpret measure of lung aspiration and functional reserve of the swallow mechanism.

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2019 TDDW

Symposium (III) NEUROGASTROENTEROLOGY AND FGID MANAGEMENT

APPROACH AND MANAGEMENT OF PATIENTS WITH REFRACTORY GERD SYMPTOMS Han-Chung Lien Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan In the last decade, gastroesophageal reflux disease (GERD) has become a prevalent disease in Taiwan. The prevalence trend was estimated to be from 10% to 25% by either endoscopy, symptoms, or the use of proton pump inhibitors.

Evidence has showed that nearly 40% of patients reported no response or partial response to PPI therapy. Given the fact of impaired quality of life in untreated GERD, refractory GERD symptoms remain a heavy burden in our society.

There has been no consensus regarding the definition of refractory GERD. Asian consensus defined as persistent troublesome GERD symptoms after a 8-week of standard dose of PPI treatment. The causes of refractory GERD symptoms are heterogenous. Firstly, to approach these patients is to re-examine whether there are alarm features to exclude any malignancies or life threatening diseases, in which an EGD exam is essential. Secondly, life style modifications such as weight reduction, avoidance of night meats, and head elevation during sleep, may be emphasized. However, little is known about the effects of dietary or lifestyle intervention. Thirdly, observational studies have shown that inadequate adherence of PPI timing or dosing may account

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for residual acid reflux. Besides, split or double dose of PPI, shift to another PPI, or add-on H2RA or alginate may be effective to a subset of patients. Fourthly, the ongoing symptoms such as regurgitation or heartburn/chest pain may guide the medical management. Fifthly, if available, a reflux monitoring is helpful in determining the etiologies of refractory GERD symptoms. Given the common etiologies of reflux hypersensitivity or functional heartburn, off-PPI test is recommended in patients with unproven GERD, such as negative endoscopy or Los Angeles Grade A or B esophagitis, to exclude reflux as the cause of symptoms. In those with proven GERD such as previous abnormal acid exposure time by pH testing, biopsy-proven Barrett’s esophagus, esophageal peptic stricture, or Los Angeles Grade C or D esophagitis, on-bid-PPI test is recommended to determine the residual acid reflux or symptoms association with non-acid or weakly acidic reflux. Pain modulators or antidepressants in low dose may be helpful in patients with reflux hypersensitivity or functional heartburn. Finally, the alternative diagnoses should be considered such as achalasia or gastroparesis or eosinophilic esophagitis.

2019 TDDW

Symposium (III) NEUROGASTROENTEROLOGY AND FGID MANAGEMENT

APPROACH AND MANAGEMENT OF PATIENTS WITH DYSPHAGIA Yen-Po Wang Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Dysphagia is defined as any subjective or objective difficulty in swallowing a liquid, semisolid or solid bolus or saliva and coughing or choking during swallowing. Dysphagia can be further categorized into oropharyngeal dysphagia or esophageal dysphagia according to clinical presentation.

For orpharyngeal dysphagia, videofluroscopy and fiberoptic endoscopic evaluation of swallowing are often used for evaluation of disease severity and further rehabilitation management.

For esophageal dysphagia, endoscopy is useful in differentiating obstructive and nonobstructive dysphagia. Barium esophagography can be used for both structural and functional evaluation while timed barium esophagography can reflect the severity of dysphagia objectively.

Esophageal manometry can be used to detect

esophageal motor disorders. The high resolution esophageal manometry (HRM) result can be subcategorized according to Chicago’s classification criteria version 3.0 for further management. For dysphagia patients with discordant result in studies mentioned above, EndoFLIP- a kind of high resolution impedance planimetry which can be used to measure the distensibility of esophagus is promising in guiding dysphagia management.

In treatment, for obstructive dysphagia, surgery, endoscopic dilation or stenting and gastrostomy or jejunostomy can help relieve symptoms. For esophageal motility disorders, surgery (esophagectomy or laparoscopic Heller’s myotomy), endoscopic therapy (per-oral endoscopic myotomy, pneumatic dilation, botox injection) or medication (calcium channel blocker, nitrates) are used for management accordingly.

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2019 TDDW

Symposium (IV) GASTROINTESTINAL POLYPOSIS SYNDROME

OVERVIEW OF GI POLYPOSIS SYNDROME Chi-Ming Tai Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan Gastrointestinal polyposis refers to the presence of numerous polypoid lesions throughout the GI tract. Gastrointestinal polyposis syndromes include numerous entities, some of which are clinically and genetically well characterized; in the case of others, research into their causes and delineation of their phenotypes has only just begun.

Gastrointestinal polyposis syndromes can be divided into inherited and non-inherited.

Inherited gastrointestinal polyposis syndromes include familial adenomatous polyposis, the hamartomatous familial polyposis (Juvenile polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Bannayan- Riley-Ruvalcaba syndrome, hereditary mixed polyposis syndrome, Gorlin syndrome, Birt-Hogg-Dube syndrome, neurofibromatosis typeI and multiple endocrine neoplasia syndrome 2B), Li-Fraumeni syndrome, and MUTYH- associated adenomatous polyposis.

Non-inherited gastrointestinal polyposis

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syndromes include Cronkhite-Canada syndrome, hyperplastic polyposis, lipomatous polyposis, Nodular lymphoid hyperplasia, inflammatory polyposis and lymphomatous polyposis.

Recognition and correct differential diagnosis of the polyposis syndromes is essential, because polyposis patients have a high lifetime risk of gastrointestinal and extraintestinal carcinoma and their first-degree relatives a high risk of recurrence of the syndrome. The initial diagnostic workup is based on the endoscopic and histological findings, together with any extraintestinal manifestations and the family history. Most polyposis syndromes can be confidently distinguished on the basis of the number and distribution of polyps in the gastrointestinal tract, and, especially, on the basis of polyp type. However, different syndromes can resemble each other phenotypically, and molecular genetic studies are important for differential diagnosis and for assessing the risk of recurrence.

2019 TDDW

Symposium (IV) GASTROINTESTINAL POLYPOSIS SYNDROME

IMAGE DIAGNOSIS OF GASTROINTESTINAL POLYPOSIS SYNDROME Tien-Yu Huang Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Gastrointestinal (GI) polyposis refers to the presence of numerous polypoid lesions throughout the gastrointestinal tract. Traditionally, the GI polyposis syndromes were classified into inherited polyposis syndromes and non-inherited polyposis syndromes. The actual diagnosis of these GI polyposis syndromes replies on the clinical presentations, image findings, genetic screening, and endoscopic appearances.

Although endoscopy should be the standard

tool for initial evaluation and diagnosis, image ďŹ ndings from those non-invasive procedures (e.g. small intestinal series, barium enema, abdominal computed tomography, CT colonoscopy, capsule endoscopy, and CT/MR enterography) could provide additional evidences for diagnosis of GI polyposis syndromes. In my talk, I will mention about the overview of image findings of GI polyposis syndromes.

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2019 TDDW

Symposium (IV) GASTROINTESTINAL POLYPOSIS SYNDROME

GENETIC DIAGNOSIS AND TREATMENT FOR GI POLYPOSIS SYNDROME Chen-Wang Chang Department of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan Colorectal cancer (CRC) is one of the leading causes of cancer-related death in Taiwan, and the incidence is rising. Rare hereditary GIl polyposis syndromes that predispose to CRC have provided a model for the investigation of cancer initiation and progression in the general population.

Although hereditary CRC syndromes are rare, it is of great importance that clinicians recognize these syndromes so they can make appropriate management decisions for both the patient and their family members who may also be at risk.

Although there are many GI polyposis syndromes, the most important GI polyposis syndromes are familial adenomatous polyposis (FAP), MUTYHassociated polyposis (MAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and serrated polyposis syndrome (SPS).

Except of gene test, endoscopy is a good tool for diagnosis of GI polyposis syndrome. In classic FAP, the endoscopic may find more than 100

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adenomas in colon/ rectum at age 25. In patient of MAP, 20-100 adenomas in colon/rectum may be found. Peutzâ&#x20AC;&#x201C;Jeghers syndrome may showed polyps in the entire GI tract with mucocutaneous pigmentations. Juvenile polyps, like PJS, are present in the colon/rectum or in other parts of the gastrointestinal tract. In SPS, more than 5 serrated polyps proximal to the sigmoid with â&#x2030;Ľ2 being >10 mm or more than 20 serrated polyps of any size distributed throughout the colon.

Endoscopic surveillance and management of GI polyposis syndrome is necessary. Due to the CRC risk is high in FAP/ MAP, remove all polyps more than 5mm is necessary. Some times, colectomy maybe need. In PJS and JPS, elective polypectomy for polyps more than 10mm is adequate. In SPS, remove all polyps more than 5mm and all polyps of any size with optical suspicion of dysplasia is necessary.

2019 TDDW

Symposium (IV) GASTROINTESTINAL POLYPOSIS SYNDROME

GENETIC DIAGNOSIS AND TREATMENT FOR GI POLYPOSIS SYNDROME Sunny H. Wong Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Cancer is a complex disease influenced by an interplay between host genetic and environmental factors. The advent of genotyping, sequencing and bioinformatics technologies has expedited the discovery of genetic aberrations underpinning different cancers. The genetic architecture of many gastrointestinal cancers

have been identified, especially for familial polyposis syndromes in which strong genetic susceptibility and high disease penetrance is characteristic. In this session, I will discuss genetic mutations associated with gastrointestinal polyposis syndrome, and their relevant diagnostic and management approach.

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2019 TDDW

Symposium (V) BILIOPANCREATIC DRAINAGE

MOLECULAR ASPECT OF BILIOPANCREATIC OBSTRUCTION Andrew Wang Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA Accurate diagnosis of the etiology of biliary and pancreatic obstruction is essential in ensuring that patients receive the correct treatment. However, standard endoscopic methods of diagnosing the causes of biliary and pancreatic duct strictures, especially when no mass lesion is evident on cross-sectional imaging or on endosonography, can be challenging.

The sensitivity for brush cytology and/or biliary biopsies is low for malignant pancreatobiliary strictures. Adjunctive endoscopic imaging techniques now exist that can help differentiate malignant from benign bioliopancreatic strictures using vascular, cellular, or even molecular distinctions.

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This presentation will describe the use of image-enhanced modalities of narrow-band imaging and autoďŹ&#x201A;uorescense and the techniques of probe-based confocal endomicroscopy and optical coherence tomography in diagnosing the cause of biliopancreatic obstruction. Adjunctive molecular techniques, such as ďŹ&#x201A;uorescence in situ hybridization and next generation sequencing will also be discussed. While not yet a commerciallyavailable diagnostic tool to aid in the endoscopic diagnosis of biliopancreatic obstruction, plectin has been found to be a promising biomarker for pancreatic ductal adenocarcinoma and possibly cholangiocarcinoma, which might also have therapeutic applications.

2019 TDDW

Symposium (V) BILIOPANCREATIC DRAINAGE

HILAR STRICTURE DRAINAGE Jong Ho Moon Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon/Seoul, Korea Hilar malignant biliary strictures (MBS) usually present in an already advanced and inoperable condition. Endoscopic biliary stenting allows adequate biliary internal drainage in most patients with MBS. Self-expandable metal stents (SEMSs) are preferred over plastic stents because of their longer patency and fewer additional endoscopic procedures. Although unilateral drainage may provide adequate drainage in some instances, bilateral drainage can provide longer cumulative patency and may drain >50% of the liver volume that is the target volume for adequate biliary drainage. However, bilateral metallic stenting for the hilar MBS remains technically challenging even for expert biliary endoscopists, especially for cases of high-grade MBS. Bilateral metallic stenting for hilar MBS is usually performed using a “side-by-side” technique, where two SEMSs are placed in parallel, or a “stent-in-stent” method,

where the second SEMS is placed through the interstices of the first one. Although the stentin-stent method is technically difficult, recently developed stents have facilitated bilateral stenting for hilar MBS. Bilateral stenting and revision with this new SEMS were feasible and effective for hilar MBS. Thus, the technical challenges of bilateral placement of SEMSs seem to have been overcome to some degree with these advances. However, the duration of stent patency and procedure-free survival remain variable. In addition to biliary drainage, endoscopic intraductal tumor ablation such as photodynamic therapy or radiofrequency ablation is possible and to be a prolongation of stent patency. Technical development and continuous evolution of metal stent can bring the better success and long-term results for hilar MBS.

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2019 TDDW

Symposium (V) BILIOPANCREATIC DRAINAGE

SURGICAL INTERVENTION OF BILIARY OBSTRUCTION Shen-Nien Wang Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Patency of the biliary tree and free bile flow into the intestine are important for normal liver function. Biliary obstruction of different etiologies often causes an impairment of bile flow out of the porta hepatitis through the biliary ducts into the duodenum. In the context, substances, which are normally excreted into the bile, will accumulate in the vascular system. Thus, patients with biliary obstruction not only present with clinical jaundice, but also lead to several systemic adverse effects and, finally, mortality. Other common symptoms include fatigue, pruritus, pale-colored stools and xanthoma. Abdominal pain may or may not be present depending on the underlying cause of the liver disease. The diseases causing biliary obstruction can be categorized into three different types; intraluminal obstruction of the biliary

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ducts, obliteration of the biliary ducts themselves, and extrinsic compression of these ducts. In most cases, surgery provides the optimal way to definitely treat them. However, obstructive j a u n d i c e e a s i l y d e v e l o p s c o a g u l o p a t h y, hypovolemia, and endotoxemia over time. It is said that successful biliary drainage can significantly improve the perioperative prognosis in patients with obstructive jaundice, especially caused by malignancies. To date, the commonly used drainage methods are percutaneous transhepatic biliary drainage and endoscopic biliary drainage. In today’s talk, we will review the etiologies of biliary obstruction, the systemic effects from obstructive jaundice, efficacies of different perioperative biliary drainage and surgical options for different biliary obstruction.

2019 TDDW

Symposium (V) BILIOPANCREATIC DRAINAGE

PANCREATIC DUCT STENTING Cheuk-Kay Sun Department of Hepato-Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan One of the most common strategies of pancreatic endotherapy is pancreatic stenting.

Stenting of the main pancreatic duct has been used to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. It has also been a useful tool to relieve ductal obstruction, often in the setting of refractory pain from strictures, stones, or papillary stenosis. In addition, stenting of the minor papilla has been used in the treatment of symptomatic pancreas divisum secondary to a stenotic minor papilla.

Pancreatic sphincterotomy with or without biliary sphincterotomy, stricture dilation with balloon dilator or dilating catheters may be required before pancreatic plastic stenting. The size of pancreatic stents usually ranges from 3 to

10 French. Stents are available in diďŹ&#x20AC;erent shapes, sizes, and numbers of barbs/flanges or pigtails.

The choice of stent is inďŹ&#x201A;uenced by the severity of the stricture, its location, and the diameter of the pancreatic duct.

There is an inherent risk of complications with pancreatic stenting. The principal early complications include stent migration, acute pancreatitis, pain, perforation and infection.

Late complications include pancreatic ductal and parenchymal changes. Proper selection of guidewire, dilator, and stent as well as refined techniques of stent placement and removal can minimize the inherent risk associated with pancreatic stenting and should be emphasized.

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2019 TDDW

Symposium (VI) PANCREATIC CANCER – TREATMENT APPROACHES AND TRENDS

CURRENT TRENDS OF MANAGEMENT IN PANCREATIC CANCER Jin-Young Jang Department of Surgery, Seoul National University Hospital, Seoul, Korea Pancreatic cancer has been known very lethal neoplasm with dismal prognosis. However, recent advance in surgery and medical oncology with knowledge of tumor biology could make continuous improvement of treatment outcome.

Recent major trends of pancreatic surgery is centralization, standardization, popularization of minimally invasive surgery and evidence based surgery, In this lecture I will talk about this changing trends in the surgical management of pancreas surgery.

Compared to other parts, the promising agents for pancreatic cancer is lacking. After the era of FOLFIRINOX or Gem-Abraxane, there has been big changes in our treatment on pancreatic cancer.

Due to the improved oncologic response of new chemotherapeutic agent, the survival of the patients with BRPC and LAPC has been improved. Based on many retrospective and our prospective study, the survival gain of neoadjuvant treatment was proved in the BRPC patients.

According to our RCT, the median survival of

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BRPC after neoadjuvant treatment based on gemcitabine based CCRT was two times higher with R0 resection rate compared to upfront surgery. With this improved oncologic outcome, some of group reported outstanding survival outcome of resected cases after chemo(radio) therapy even in unresectable, pancreatic cancer in highly selected patients with good response.

According to the recent report of nationwide multicenter study, the objective response rate was 21% in FOLFILINOX in LAPC. Although, the general role of conversion surgery must be determined based on well controlled study not highly selected patients, the role of surgical resection for advanced pancreatic cancer could be beneficial. With the development of promising systemic treatment, the multidisciplinary approach for the pancreatic cancer would be very different and role/indication of surgical resection is also changing.

In this lecture, I would like to summary the current status of treatment of pancreatic cancer and talk about the role and types of surgical resection.

2019 TDDW

Symposium (VI) PANCREATIC CANCER – TREATMENT APPROACHES AND TRENDS

THE IMPACT OF TUMOR MICROENVIRONMENT IN PANCREATIC CANCER Yan-Shen Shan Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan Pancreatic cancer is a formidable disease.

Though there is great improvement in medicine, the prognosis is still poor with 5-year survival rate around 5% today. There are several reasons contribute for poor outcome, such as unknown tumor biology, delay in diagnosis with lower resectability, resistant to chemotherapy and radiotherapy, special role of pancreas in GI function (nutrition and GI motility).

Pancreatic cancer microenvironment is different from most of the cancer. The unique picture is desmoplasia, presents with prominent fibrosis in the microenvironment. It is considered as the most important factor for chemoresistance, because the fibrosis will increase the hydrostatic pressure of vessels, which further hinder the blood flow and diffusion of drugs into the tumor.

Furthermore, the microenvironment consists of fibroblasts, immune cells, pancreatic stellate cells (PaSCs), adipocytes and extracellular matrix (ECM) will further increase the invasiveness of cancer cells.

Nanodrugs, including abraxane and onivyde, can increase diffusion active components into tumormicroenvironment but only shows modest benefit. Several therapeutic regimens targeting PDAC microenvironment factors or cells have been investigated, the treatment effects were poor. Our translation studies prove the interplays among tumor cells, immune cells, and PaSCs determine the poor outcome. Therefore, more research on the physiological and pathological mechanisms and clinical treatment of PDAC is necessary in future.

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2019 TDDW

Symposium (VII) THE CLINICAL IMPLICATION OF PROBIOTICS

THE HEALTH IMPACT AND EFFECT OF HERB MEDICINE MEDIATED INTESTINAL PROBIOTICS Hsin-Chih Lai Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan We h a v e p r e v i o u s l y r e p o r t e d t h a t a bacterial Parabacteroides goldsteinii strain that was enriched by administration of TCM (Ophiocordyceps sinensis and Ganoderma lucidum) and their high molecular weight polysaccharides, showed significant effect on amelioration of obesity, NAFLD and metabolic syndromes in a mono-association manner.

In this study, we set out to characterize the bacterium’s function in relation to other chronic inflammation related diseases. The CRC and COPD animal models were used for test. Our

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results indicated that CRC and COPD were significantly ameliorated by oral administration of this bacterium. Further Germ free models and multiomics study using metagenomics, transcriptomics (single cell RNAseq) and metabolomics highlighted the underlying complicated biochemical mechanisms of P. goldsteinii amelioration. On top, an active component derived from this bacterium was identified and showed ameliorative effects. Novel probiotics and postbiotics that can show antiobesity, anti-CRC and anti-COPD are expected.

2019 TDDW

Symposium (VII) THE CLINICAL IMPLICATION OF PROBIOTICS

PSYCHOBIOTICS AND NEURODEVELOPMENT DISORDERS Ying-Chieh Tsai Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan Neurodevelopmental disorders, such as autism spectrum disorder (ASD), Tourette syndrome, dyslexia, and attention deficit hyperactivity disorder, are due to abnormal brain development at early age. Recent studies have revealed that gut microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders through the microbiome-gut-brain axis (MGBA).

Psychobiotics, a class of probiotics with psychotropic activities, integrate neural, hormonal, and immunological signaling via the MGBA have proved for combating a broad spectrum of complex diseases including mental illness, neurodegenerative disorders and neurodevelopmental disorders. Lactobacillus plantarum PS128 (PS128) is a novel psychobiotic, which normalized depression-like behaviors in early life-stressed mice, reduced the 5-HTPinduced visceral hypersensitivity in a rat model of IBS, and improved locomotion in Parkinson’s

disease-like mice.

Here, we report the effect of PS128 on 2,5-Dimethoxy-4-iodoamphetamine (DOI)induced Tourette syndrome-like rat model, and results of a randomized, double-blind, placebocontrolled (RCT) trial of ASD. In the DOI-induced Tourette syndrome-like rat model, PS128 administration ameliorated DOI-induced tic-like hyper-active behaviors via stabilizing cerebral dopaminergic pathways through modulation of the host’s MGBA. In the RCT trial of ASD, PS128 administration appeared to reduce scores on body and object use, hyperactivity/impulsivity, opposition/defiance, anxiety, problems related to thoughts, and rule-breaking behaviors, comparing with the placebo.

These results of behavioral tests in rodents and the ASD clinical study suggest that PS128 is a feasible and natural intervention for alleviating symptoms of neuropsychiatric disorders.

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2019 TDDW

Symposium (VII) THE CLINICAL IMPLICATION OF PROBIOTICS

MICROBIOTA, PROBIOTICS AND THE LONG-TERM IMPACT OF HEALTH CARE DEVELOPMENT Shih-Yen Chen Department of Pediatrics, Shuang Ho Hospital Taipei Medical University, Taipei, Taiwan Human microbiome exists in unique, complementary blends, and inhabits everything from our skin and genitals, to our mouths and eyes, and of course our intestines. The clusters of bacteria from different regions of the body are variously known as microbiota. These microbes have tremendous potential to impact our physiology, both in health and in disease. They contribute metabolic functions, protect against pathogens, educate the immune system, and, through these basic functions, affect directly or indirectly most of our physiologic functions.

Microbiome management including microbiota seeding, feeding, and rebiosis appears likely to be a core component of a path toward sustainable healthcare. Effective isolation depends on medium formulation, fermentation conditions, time, temperature and atmosphere of incubation.

Culture media and incubation conditions were recommended for the growth capability of probiotics.

Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. The developing intestinal microbiome and its relationship to health and disease in the neonate. Gut microbial metabolites have been implicated as novel risk factors for cardiovascular events and premature death. Gut dysbiosis, reduced intestinal motility and increased intestinal permeability, that allow

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bacterial products to circulate and pass through the blood-brain barrier, are associated with neurodegenerative disease.

Diet can be a modifier of the gut microbiome (e.g., its composition and functional attributes).

Gut microbiota are capable of furtherer metabolizing dietary bioactives to generate secondary bioactive compounds, and microbiallyderived metabolites can act on epithelial cells in the colon by extrinsic and intrinsic mechanisms to reduce colon cancer risk. Disruption of the developing microbiota in infancy contributes to the risk of immune and metabolic disease in later life, whereas loss of microbes in the elderly due to monotonous diets has been linked with unhealthy ageing and frailty.

There has been increasing interest in understanding the role of the human gut microbiome to elucidate the therapeutic potential of fecal microbiota transplantation (FMT) since the first case reported in 1983 by Schwan et al. Studies and applications of fecal microbiota transplantation (FMT) include Clostridium Difficilei infection, inflammatory bowel disease (Ulcerative colitis, Crohn’s disease), irritable bowel syndrome (Constipation), liver cirrhosis, antimicrobial resistant organism (MDROs), acute pancreatitis, acute-graft-versus-host disease, metabolism (obesity, DM), parkinson’s disease, and autism.

Results from clinical studies are conflicting, which reflects the gap in our knowledge of the

2019 TDDW microbiome composition and function, and highlights the need for a more defined and personalised microbial isolation and transfer.

The fecal bank organization OpenBiome, dedicated to expanding safe access to fecal microbiota transplants (FMT), and to catalyzing research into the human microbiome. Many links between gut microbiota and disease development have been established in recent years, with particular bacterial strains emerging as potential

therapeutics rather than causative agents. Recent study described immunostimulatory properties of Enterococcus gallinarum MRx0518, a candidate live biotherapeutic with proven anti-tumorigenic eďŹ&#x192;cacy.

Great progress in characterizing the structure of the microbiome recently has paved the way for ongoing and future studies on the functional interactions between the microbiota and the host, highlighting the long-term health care of human.

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2019 TDDW

Symposium (VIII) GEST-KASID JOINT SYMPOSIUM

DEESCALATION OF BIOLOGICS â&#x20AC;&#x201C; CONS Sung-Ae Jung Gastroenterology & IBD Center, Ewha Womans University Meidcal Center, Seoul, Korea Biologics have recently become the major part in IBD treatments significantly improving the disease management. Despite considerable advances of various biologics, dose adjustment during the treatment is still needed for IBD patients due to the delineated disease course by periods of remissions and relapses. Clinically, we already have experienced that proper dose escalation is significant in IBD treatment optimization. Therefore, dose escalation or deescalation of biologics is currently one of the most important topics related to IBD treatment. This review is an opposing suggestion of stopping or de-escalating the biologics in IBD patients who had been maintaining their stable remission status.

Risk of relapse reported after withdrawal or reduction of biologics is still high. Many efforts

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including the TDM-based strategy have been constantly applied to reduce the recurrence rate of disease and predict the risk of relapse, but still, dose reduction or discontinuation of biologics seems quite risky. Continuous monitoring of any alert sign of recurrence could be burdensome for both the patient and physician. Also after the recurrence, the patient would suffer from relapsed symptoms and the treatment group should restart the therapy again. Therefore, if any biological therapy is functional maintaining the remission state of the patient, it could be the most recommending, economic and proper choice to maintain the current treatment while working. Any consideration of dose de-escalation or discontinuation of biological treatment should always be discussed carefully between the IBD patient and physician.

2019 TDDW

Symposium (VIII) GEST-KASID JOINT SYMPOSIUM

EVALUATING REMISSION OF UC: PATIENT-REPORTED OUTCOMES ARE SUFFICIENT Tien-Yu Huang Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Evaluation of remission and prediction of disease outcome in patients with ulcerative colitis (UC) are particularly important in clinical practice because treatment for UC are not always satisfactory and frequent relapse could increase the complications and risk of colectomy. Deep remission (both clinical remission and mucosal remission) is a treatment goal in management of ulcerative colitis. In addition to clinical remission, mucosal remission is also important in disease outcome and prediction of disease relapse.

Endoscopy has traditionally been considered a gold standard to evaluate mucosal status in UC patients. However, undergoing endoscopy is invasive and burdensome to patients.

One initial goal of treating patients with

UC is to achieve the remission of symptoms.

Rectal bleeding and stool frequency are used in clinical practice and clinical trials to evaluate the therapeutic responses in UC patients.

Recent studies found that these patient-reported outcomes could represent the mucosal status and UC patients with normal rectal bleeding and stool frequency subscores are very likely to have mucosal remission. Therefore, meticulous evaluation of patientâ&#x20AC;&#x2122;s symptoms or combined with further measurements of non-invasive biomarkers (CRP, fecal calprotectin, or fecal immunochemical test) could be predictive for disease activity and mucosal remission in UC patients. In my talk, I will mention about the roles of patientâ&#x20AC;&#x2122;s reported outcomes in evaluation of mucosal remission in UC.

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2019 TDDW

Symposium (VIII) GEST-KASID JOINT SYMPOSIUM

ENDOSCOPIC REMISSION SHOULD BE THE ULTIMATE GOAL IN MANAGEMENT OF ULCERATIVE COLITIS Jong Pil Im Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea Introduction Ulcerative colitis (UC) is a chronic inflammatory bowel disease, its pathogenesis is still unclear. It is defined by a continuous mucosal inflammation of the rectum and a variable extent of the colon, without the formation of granuloma on biopsies.1 UC is characterized by periods of remission and periods of relapse, is responsible for the overwhelming majority of the disease burden and diminished quality of life. Patients with UC often present with symptoms such as rectal bleeding, diarrhea and weight loss, and may need hospitalization and even colectomy. Persistent and extensive active UC increases the long-term risk of colorectal cancer.2 In the past, the management in UC was focused on controlling symptoms. Symptoms assessment remains as important aspect of UC approach.3 However, this approach, directed at controlling and mitigating the consequence of inflammation, did not target the inflammatory activity itself. Moreover, there is an imperfect correlation between symptoms and inflammation at bowel, and more than half of all patients in clinical remission exhibit mucosal inflammation on endoscopy.4 There is emerging evidence suggest that achieving clinical remission without mucosal healing dose not associated with reduced rated of hospitalization or colectomy.5,6 Disease activity is limited to the mucosa in UC, unlike Crohn’s disease. Hence, it is no

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surprise that mucosal healing (MH) should prove an attractive target when aiming for improved outcomes in UC, regardless of the disease extent, inflammatory marker, or clinical presentation.

Current Definitions of MH Endoscopically, active UC may present with various mucosal abnormalities including erythema, mucosal friability and bleeding, loss of vascular pattern, erosions, and ulcers.1 The Mayo Endoscopic Score (MES), developed in 1987, is the most widely used score in clinical practice.7 It includes the variables erythema, loss of vascular pattern, friability, bleeding erosions and ulcers, and range from 0 to 3. MH is classically considered to be a score of 0 or 1.8 However, some reported that significant difference in clinical outcomes between patients with MES 0 and MES 1.9-11 The most recent ECCO guideline consider endoscopic remission as MES≤1, but complete MH as MES 0.12 The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was recently introduced in clinical practice. This score proved excellent interobserver agreement and a superior correlation with clinical outcomes, long-term prognosis, and mucosal improvement during treatment when compared with the MES.13

Prognosis Relevance of MH Since the concept of MH was introduced,

2019 TDDW several clinical trials have reported on the various outcomes of UC and the influence of several intervening factors, particularly MH. In the combined ACT1 and ACT2 trials, MH after the infliximab introduction phase was significantly associated the long-term corticosteroid-free remission (p< 0.001) and a decreased risk of colectomy (p <0.001) at both week 30 and week 54.14 Similarly, a prospective study in Italy revealed that patients in MH at 3 months of treatment for moderate to severe UC had less clinical relapse at 15 months (27.5% vs 73.9%).15 To date, a common concern is patients with longstanding UC is the increased the risk of colorectal cancer. Some evidence suggests that an increased risk of dysplasia and progression to colorectal cancer in patients with the endoscopically active disease when compared with those achieving MH.16,17

References: 1.

Dignass, A. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. Journal of Crohn’s & colitis 6, 965-990, doi:10.1016/ j.crohns.2012.09.003 (2012).

2.

Dignass, A. et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. Journal of Crohn’s & colitis 6, 991-1030, doi:10.1016/ j.crohns.2012.09.002 (2012).

3.

Levesque, B. G. et al. Converging goals of treatment of inflammatory bowel disease from clinical trials and practice. Gastroenterology 148, 37-51.e31, doi:10.1053/ j.gastro.2014.08.003 (2015).

4.

Baars, J. E., Nuij, V. J., Oldenburg, B., Kuipers, E. J. & van der Woude, C. J. Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation. Inflammatory bowel diseases 18, 1634-1640, doi:10.1002/ibd.21925 (2012).

5.

Langholz, E., Munkholm, P., Davidsen, M. & Binder, V. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107, 3-11, doi:10.1016/0016-5085(94)90054-x (1994).

6.

Turner, D., Walsh, C. M., Steinhart, A. H. & Griffiths, A. M. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 5, 103-110, doi:10.1016/j.cgh.2006.09.033 (2007).

7.

Schroeder, K. W., Tremaine, W. J. & Ilstrup, D. M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. The New England journal of medicine 317, 1625-1629, doi:10.1056/nejm198712243172603 (1987).

Conclusion UC in a chronic inflammatory disease with severe consequence, including the need for hospitalization and colectomy and increased long-term risk of colorectal cancer. Several trials demonstrated that MH has been significantly associated with improved outcomes in UC patients. In addition, MH established itself as a crucial factor in the management of the disease. Nevertheless, while clinical practice is currently adapting to the available evidence and changing from a symptom-based approach toward endoscopic-based management, so too is the definition of mucosa healing in constant adjustment.

Recent evidence take notice the importance of complete MH, not just partial MH as a preferred goal in the management of UC. Histological healing has emerged as one of the goals for UC. For achieving these goals, a perfect interaction is required between accurate endoscopic, and even histological, assessment of the disease and adequate treatment with drugs, capable not only of controlling the symptoms but quieting inflammation itself.

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2019 TDDW 8.

9.

Daperno, M. et al. Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. Journal of Crohn’s & colitis 5, 484-498, doi:10.1016/ j.crohns.2011.07.003 (2011).

Barreiro-de Acosta, M. et al. Evaluation of the Risk of Relapse in Ulcerative Colitis According to the Degree of Mucosal Healing (Mayo 0 vs 1): A Longitudinal Cohort Study.

Journal of Crohn’s & colitis 10, 13-19, doi:10.1093/ecco-jcc/jjv158 (2016).

10. Boal Carvalho, P., Dias de Castro, F., Rosa, B., Moreira, M. J. & Cotter, J. Mucosal Healing in Ulcerative Colitis--When Zero is Better. Journal of Crohn’s & colitis 10, 20-25, doi:10.1093/ecco-jcc/jjv180 (2016).

(2013).

13. Ikeya, K. et al. The Ulcerative Colitis Endoscopic Index of Severity More Accurately Reflects Clinical Outcomes and Long-term Prognosis than the Mayo Endoscopic Score.

Journal of Crohn’s & colitis 10, 286-295, doi:10.1093/ecco-jcc/jjv210 (2016).

14. Colombel, J. F. et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 141, 1194-1201, doi:10.1053/j.gastro.2011.06.054 (2011).

15. Parente, F. et al. Bowel ultrasound and mucosal healing in ulcerative colitis. Digestive diseases (Basel, Switzerland) 27, 285-290, doi:10.1159/000228562 (2009).

11. Nakarai, A. et al. Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count. World journal of gastroenterology 20, 18367-18374, doi:10.3748/wjg.v20.i48.18367 (2014).

16. Rubin, D. T., LoSavio, A., Yadron, N., Huo, D. & Hanauer, S. B. Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 4, 13461350, doi:10.1016/j.cgh.2006.08.014 (2006).

12. Annese, V. et al. European evidence based consensus for endoscopy in inflammatory bowel disease. Journal of Crohn’s & colitis 7, 982-1018, doi:10.1016/j.crohns.2013.09.016

17. Rutter, M. et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology 126, 451459, doi:10.1053/j.gastro.2003.11.010 (2004).

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2019 TDDW

Symposium (VIII) GEST-KASID JOINT SYMPOSIUM

FUTURE OF IBD PATIENT CARE – IS IT PRIME TIME FOR PRECISION MEDICINE? Dong Il Park Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea The NIH definition of precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. The overall goal of precision medicine in the inflammatory bowel diseases (IBD) field is to utilize specific clinical and biologic characteristics of individual patients for early detection, ideally at diagnosis, of patients with potentially aggressive disease course and complications, and for the prediction of response to therapy to deliver optimal care. In practice, this involves stratification of patients into precise groups, using biomarkers, and determination of the best treatment option to deliver (right drug, right dose, right time and right patient) and avoidance of unnecessary exposure to ineffective and expensive therapies for each group.

While studies over the past decade have begun to address this goal, knowledge gaps remain in terms of precisely which clinical and

biologic factors will provide the greatest utility in predicting disease course and assessing clinical outcomes in response to therapy over time.

Suggested approaches to bridge these gaps include prospective longitudinal cohort studies to identify and validate precision biomarkers for prognostication of disease course, and prediction and monitoring of treatment response.

To achieve this, harmonization across studies is key as well as development of standardized procedures related to data and sample collection, data repository, bio-sample banking and other infrastructures. The implementation of state-ofthe-art molecular technologies, systems biology and machine learning approaches for multiOMICS and clinical data integration and analysis will be also fundamental. Finally, randomized biomarker-stratified trials will be critical to evaluate the clinical utility of validated signatures and biomarkers in improving patient outcomes and cost-effective care.

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2019 TDDW

Symposium (IX) NEW FRONTIER OF DIGESTIVE ENDOSCOPY TECHNIQUE

ENDOCYTOSCOPY: NEW HORIZON OF MAGNIFYING ENDOSCOPY Haruhiro Inoue Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan Novel endocytoscopy was specially designed to observe cell nucleus as well as cellular-level structure with maintaining ordinary function of magnifying endoscopy. Outer diameter of novel endocytoscope is 9.6mm, which is smaller than currently available magnifying endoscope (H290Z). Novel endocytoscopy can be used as a standard magnifying endoscope similar to H290Z, and once tip of endoscopy touches target mucosa, approximately 400-fold magnifying image will be provided, which enable to observe cell and cell nucleus.

Routine endoscopic surveillance is as follows by utilizing newly designed endocytoscope.

In esophagus a brownish area under NBI observation is once identified, conventional magnifying observation is carried out to clarify changes of IPCL to assess tissue character.

Furthermore, endocytoscopic image will be acquired just by touching tip of endocytoscope

42

onto target mucosa with CM (crystal violet & methylene blue double staining).

Procedure details and future extension will be discussed.

References: 1.

Inoue H et al. In vivo observation of living cancer cells in the esophagus, stomach, and colon using catheter-type contact endoscope, "Endo-Cytoscopy system." Gastrointest Endoscopy Clin N Am 2004; 14: 589-594.

2.

Inoue H et al. Laser-scanning confocal microscopy and endocytoscopy for cellular observation of the gastrointestinal tract.

Nature Clinical Practice Gastroenterology & Hepatology 2005; 2: 31-37.

3.

I Inoue H et al. Endoscopic in Vivo evaluation of tissue atypia in the esophagus using a newly designed integrated endsocytoscope: a pilot trial Endoscopy 2006; 38: 891-895.

2019 TDDW

Symposium (IX) NEW FRONTIER OF DIGESTIVE ENDOSCOPY TECHNIQUE

ANTI-REFLUX MUCOSECTOMY FOR GERD: FEASIBILITY, SAFETY AND OUTCOMES Chun-Fu Ting Department of Gastroenterology and Hepatology, China Medical University Hospital, Taichung, Taiwan Refractory gastroesophageal reflux disease (GERD) remains a difficult clinical challenge.

When PPIs are ineffective, anti-reflux surgery is generally recommended, such as laparoscopic Nissen fundoplication. Recently, endoscopic alternatives to laparoscopic antireflux surgery have been carried out. In 2014, Inoue et al published a series of 10 patients that received the antireflux mucosectomy (ARMS) procedure for refractory GERD showing excellent results both subjectively and objectively, with the advantage that no artificial devices or prostheses would be left in situ.

From March 2015 to Dec 2018, we had retrospectively reviewed patients who received ARMS for treatment-refractory GERD. A total of 25 patients (10 female and 15 male patients) received 27 ARMS; 2 male patients had second ARMS due to recurrent GERD symptoms and severe hiatal hernia (Grade 3 and Grade 4).

The mean age was 43.2 years old (28-70 y/o). All

patients were diagnosed as treatment-refractory GERD, in which PPIs had been used for at least one year with refractory GERD symptoms; one female patient had recurrent GERD after fundoplication and one female patient had severe GERD after sleeve gastrectomy. At endoscopic examination, most patients had presence of hiatal hernia (23/25, 17 Grade 2, 3 Grade 3, 3 Grade 4), severe esophagitis (Los Angeles classification C:14, D:8, B:3); 8 patients have Barrett’s esophagus before ARMS. ARMS was performed with hemi-circumferential resection (40%-70%), mean procedure time 48.6 minutes, no immediate/ delayed bleeding or perforation developed. After ARMS, the total DeMeester – symptom - score decreased from 6.8 to 2.2.

ARMS showed promising safety and efficacy for patients with treatment-refractory GERD. However, the sample size was small. Patients with GERD that are considered for ARMs are those without a large sliding hiatus hernia (Grade 3 or 4).

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2019 TDDW

Symposium (IX) NEW FRONTIER OF DIGESTIVE ENDOSCOPY TECHNIQUE

GASTRIC PER-ORAL ENDOSCOPIC PYLOROMYOTOMY FOR REFRACTORY DIABETIC GASTROPARESIS Chen-Shuan Chung Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan Functional GI motility disorders account for most consultations in gastroenterology and these disorders may affect any part of the GI tract through various mechanisms and disturbing symptoms vary according to the specific organ functional impairment. Among them, gastroparesis, which is defined as a chronic delayed gastric emptying related symptoms without mechanical obstruction of the stomach or proximal small bowel, remains difficult-to-treat.

Due to limitations in medical and surgical options, patients with refractory gastroparesis usually have poor quality of life due to poor response or adverse effects from conventional therapies.

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With the advent of â&#x20AC;&#x153;third-space endoscopyâ&#x20AC;? since around 2008, wherein endoscopists had demonstrated that endoscope could breach the mucosa layer of the gut wall intentionally instead of inadvertently and enter safely into the submucosal space for further operation such as myotomy, refractory gastroparesis could be treated by peroral endoscopy efficiently and safely, so-called gastric peroral endoscopic pyloromyotomy (G-POEM). Herein, I will review the application and share experiences of this endoscopic technique in the management of refractory gastroparesis.

2019 TDDW

Symposium (X) HCC DIAGNOSIS AND THERAPIES: UPDATE AND REAL-WORLD EXPERIENCES

CLINICAL USEFULNESS OF CEUS WITH SONAZOID FOR HCC DIAGNOSIS AND THERAPIES IN REAL WORLD PRACTICE ～ 12 YEARS’ EXPERIENCE IN JAPAN ～ Kaoru Tsuchiya Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan Sonazoid (Daiichi-Sankyo Company, Tokyo, Japan) is a second-generation contrast media, which has been approved in Japan since Jan 2007. It consists of perfluorobutane microbubbles with phosphatidyl serine membrane and stable CEUS imaging can be obtained without obvious microbubble destruction. In addition, sonazoid has high affinity with Kupffer cells in the liver. After 10 minutes from the injection, we can scan the whole liver as the Kupffer phase (post-vascular phase).

Sensitivity of liver tumor detection using EOBMRI is better than CEUS with sonazoid, however previous reports revealed that some nonHCC tumors including dysplastic nodules were detected as hypointensity lesions in hepatobiliary phase of EOB-MRI. One of the most important roles of CEUS with sonazoid is to distinguish HCC from non-HCC tumors which are detected by using EOB-MRI. Furthermore, CEUS imaging with sonazoid would become a biomarker in early stage HCC. Intratumor vascular structure and Kupffer imaging are associated with pathological

findings and local recurrence after ablation therapy. The other valuable role of CEUS with sonazoid is to assist the local ablation therapy for HCC. The success rate of RFA using CEUS with sonazoid was reported as 90-100% in Japan. Reinjection method is also useful when we perform ablation therapy in patients with local recurrence after RFA or TACE. The new remarkable role of CEUS with sonazoid is the accurate diagnosis of tumor vascularity during tyrosine kinase inhibitors (TKIs), especially lenvatinib therapy in patients with unresectable HCC (BCLC stage B and C). After administration of lenvatinib, tumor enhancements in arterial phase at MDCT are often decreased, however, when we evaluate the tumor vascularity by using CEUS with sonazoid, it still remains in most cases. In conclusion, CEUS with sonazoid has great impact on HCC diagnosis and therapy and further progresses would be expected with improving US equipment and their applications.

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2019 TDDW

Symposium (X) HCC DIAGNOSIS AND THERAPIES: UPDATE AND REAL-WORLD EXPERIENCES

EARLY STAGE HCC: ABLATION Kai-Wen Huang Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan Surgical resection has long been considered the gold standard for the local treatment of hepatocellular carcinoma (HCC). Until recent years, percutaneous local ablation, in particular radiofrequency ablation (RFA), was not accepted as a first-line option for the treatment of liver tumors and was reserved for patients who were unsuitable for surgery. However, in the last decade the scenario has changed: innovative technical developments have improved the performance of local ablation and broadened the availability of other ablative technologies.

Nowadays, there is an increasingly accepted consensus on the role of local ablation as a ďŹ rstline option for the treatment of early, small liver tumors, as well as in patients potentially eligible for surgery.

Ablation is potentially curative, minimally invasive, and easily repeatable for recurrence.

Radiofrequency ablation has recently been the most prevailing ablation method for HCC from the viewpoints of treatment response, local tumor

46

curativity, and overall survival. New-generation microwave ablation can create a larger and spherical ablation in a shorter time period. Further comparison studies are, however, mandatory between radiofrequency ablation and microwave ablation, especially in terms of complications and long-term survival. Irreversible electroporation, which is a non-thermal ablation method that delivers short electric pulses to induce cell death due to apoptosis, requires further studies, especially in terms of long-term outcomes. It is considerably difficult to compare outcomes in ablation with those in surgical resection. However, radiofrequency ablation seems to be a satisfactory alternative to resection for HCC 3 cm or smaller in Child-Pugh class A or B cirrhosis. Furthermore, radiofrequency ablation may be a first-line treatment in HCC 2 cm or smaller in ChildPugh class A or B cirrhosis. Various innovations would further improve outcomes in ablation.

Sophisticated ablation with adequate device would be more than an adequate alternative of surgery for small- and possibly middle-sized HCC.

2019 TDDW

Symposium (X) HCC DIAGNOSIS AND THERAPIES: UPDATE AND REAL-WORLD EXPERIENCES

INTERMEDIATE STAGE HCC: TACE MONOTHERAPY OR COMBINE SYSTEMIC THERAPY Chen-Chun Lin Division of Hepatology, Liver Research Unit, Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan Hepatocellular carcinoma (HCC) is the second cancer death both in the world and in Taiwan. Transarterial chemotherapy (TACE) is the most widely used for the patients in this stage.

The survival benefits have been confirmed by the 2 randomized controlled studies in which demonstrated the overall survival prolonged from 20 months by best supportive treatment to 26 months by TACE. The 2-year survival benefits have been confirmed by several metaanalysis studies. The objective response rate was about 52.5%, while adverse event with liver function abnormalities were found in one fifth of the patients. Repeat TACE might benefit some patients; however, risk of liver failure is also increasing. Local hypoxia and ischemic necrosis induced by TACE results in activation of HIF and increase of VEGF. Both factors are responsible to tumor regrowth and causing tumor recurrence. Molecular target therapy (MTT) inhibit the receptor or pathway of these factors.

Theoretically, MTT combined with TACE should have synergistic effects. However, in the recent

large randomized controlled trials only showed the acceptable safety profiles and have the capacity to delay tumor progression but failure to proven prolongation of overall survival. Delay starting and early termination of MTT might be the cause of failure in these trials. One recent phase II study modified the combination protocol with apply of sorafenib 2-3 weeks ahead of TACE and continuous therapy not be terminated by new intrahepatic tumors. The duration of sorafenib could have as long as 38.7 months and the progression-free survival had a maximum value up to 25.2 months, although the benefit on overall survival was still insignificant. Checkpoint inhibitor (ICI) inhibit PD1 or PDL1 ligands causing activation of cytotoxic T cell to kill tumors. TACE help to directly damage HCC and increase the exposure of tumor antigens. Combination of ICI with TACE might have synergistic antitumor effects. Further studies have on the way and these studies are expected to have positive results in the future.

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2019 TDDW

Symposium (X) HCC DIAGNOSIS AND THERAPIES: UPDATE AND REAL-WORLD EXPERIENCES

ADVANCED STAGE HCC: SYSTEMIC THERAPIES: TAIPEI VGH REAL-WORLD EXPERIENCE AND CURRENT UPDATE Yi-Hsiang Huang Division of Gastroenterology & Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Immune checkpoint inhibitors (ICI), mainly anti-PD-1 treatment have been demonstrated their positive responses in advanced HCC patients failed to sorafenib treatment. Nivolumab (anti-PD1) is the first FDA-approved immune checkpoint inhibitor for HCC. A phase I/II trial (CheckMate 040) for HCC patients who were sorafenib naive, sorafenib intolerant or sorafenib refractory were treated with nivolumab. Such treatment yielded a promising efficacy, with objective response rate of 14% and 9-month survival rate of 74%. Pembrolizumab, another antibody against PD1, showed a similar response rate as nivolumab in an open-label, phase 2 trial (Keynote 224) of HCC patients either intolerant to sorafenib or disease progression after the

48

sorafenib treatment. Among 104 patients, 1 complete response and 16 partial responses were observed. The median time of overall survival was 12.9 months. More recently, a second-line phase 3 trial (Keynote 240) had demonstrated a similar response rate to pembrolizumab in advanced HCC after sorafenib failure. Although this trial did reach its prespecified p value, a significant portion of advanced HCC patients did respond to immunotherapy. However, only less than 20% of treated patients show an objective and durable response to the immunotherapy from clinical trials, and there was still no practical biomarker, including the level of PD-L1 expression to predict tumor response. A real-world experience from Taipei VGH will be presented in this presentation.

2019 TDDW

Symposium (XI) SARCOPENIA AND LIVER DISEASE

SARCOPENIA IN LIVER DISEASE Jin Mo Yang Department of Internal Medicine, Stâ&#x20AC;&#x2122; Vincent Hospital, Catholic University Medical College, Suwon, Korea Sarcopenia is characterized decline of skeletal muscle mass and low muscle strength or physical performance. Sarcopenia is common in liver cirrhosis, and is associated with nonalcoholic fatty liver disease (NAFLD). The mechanisms that contribute to sarcopenia include inadequate dietary intake, metabolic disturbances, and malabsorption in cirrhosis. In NAFLD, sarcopenia is caused by insulin resistance and chronic inflammation. Muscle mass can be assessed b y c o m p u t e d t o m o g r a p h y, a n d h a n d g r i p strength is used for assessing muscle strength.

Sarcopenia adversely affects transplant waitlist mortality, post-transplant survival, hepatocellular carcinoma survival and development of hepatic encephalopathy. Frailty is also associated with waitlist mortality. Sarcopenia is associated with hepatic fibrosis and inflammation in NAFLD. To improve sarcopenia, some guidelines recommend appropriate nutritional support. In addition exercise has multiple benefits for sarcopenia. Here, we provide a brief review about the pathogenesis, diagnosis, clinical impact, and treatment in chronic liver disease.

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2019 TDDW

Symposium (XI) SARCOPENIA AND LIVER DISEASE

THE EVALUATION AND DIAGNOSIS OF SARCOPENIA Der-Sheng Han Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with adverse outcomes including falls, fractures, physical disability, comorbidity, and mortality. The original definition of sarcopenia by European Working Group on Sarcopenia in Older People in 2010 was low muscle mass plus weak muscle strength or poor muscle function. Specific appendicular skeletal muscle mass index (aSMI) measured by dual energy X ray absorptiometry below 7.0 kg/m2 in male and 5.4 kg/m2 in female is deemed as low muscle mass. Grip strength below 26kg in male and 18kg in female is weak muscle.

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Those having usual gait speed lower than 0.8m/ sec are slow walker. Among the comorbidities, liver diseases have tremendous impact on both individual and societal expenditure. Since patients with hepatoma usually had abdominal CT scan to stage their tumor status, we then determined skeletal muscle mass by CT scan through L3.

Skeletal muscle mass index below 36.0 cm2/m2 in male, and 29.0 cm2/m2 in female is deemed low, which is equivalent to above-mentioned aSMI values. Low skeletal muscle mass is related with high mortality, high tumor recurrence, and higher rate of hepatic encephalopathy.

2019 TDDW

Symposium (XI) SARCOPENIA AND LIVER DISEASE

IMAGING FOR LIVER CIRRHOSIS-RELATED SARCOPENIA Yu-Ching Lin Department of Radiology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan Sarcopenia is part of the frailty complex present in cirrhotic patients, resulting from cumulative declines across multiple physiologic systems and characterized by impaired functional capacity, decreased reserve, resistance to stressors, and predisposition to poor outcomes. At present, Child-Pugh, and MELD scores constitute the best tools to predict mortality in patients with cirrhosis; however, one of their main limitations is the lack of assessing the nutritional and functional status. Currently, numerous methods are available to evaluate the nutrition status of the cirrhotic patient; nevertheless, most of these

techniques have limitations primarily because lack of objectivity, reproducibility, and prognosis discrimination. In this regard, an objective and reproducible technique, such as muscle mass quantification with imaging studies (computed tomography scan or DXA) constitute an attractive index of nutritional status in cirrhosis. In this talk, we discuss the current accepted and new methods to evaluate prognosis in cirrhosis. Also, we analyze the current knowledge regarding incidence and clinical impact of malnutrition and sarcopenia in patients with cirrhosis.

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2019 TDDW

Symposium (XI) SARCOPENIA AND LIVER DISEASE

NUTRITIONAL INTERVENTIONS IN SARCOPENIA Ming-Tsan Lin Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan The liver plays central roles in nutrition and metabolism. Carbohydrate, lipid and amino acid/ protein metabolism disturbance may occur in liver disease. Interorgan metabolic responses among brain, liver, intestine, liver and other organs are accelerated during disease and stress.

Sarcopenia and lean body mass lose are associated with may clinical conditions including liver diseases. Factors of causing sarcopenia are endocrine-related, aging, inadequate nutrition, neurological disturbance, disuse, tumor-derived factors, drugs, surgery, etc. Hospitalization, chronic diseases, and ICU/cachexia may enhance

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muscle loss. Sarcopenia consequences patientâ&#x20AC;&#x2122;s function impair, metabolic disturbance, disability, mortality and increased hospital stay.

Nutrition screening and assessment should be done in liver disease. Nutrition intervention will be discussed and stressed in various clinical conditions. Optimal nutritional routes, major and micro-nutrients may be administrated and will be demonstrated.

In summary, nutritional intervention is important in supporting sarcopenia and treatment for liver diseases.

2019 TDDW

Symposium (XII) GUT MICROBIOME AND HUMAN DISEASES: CURRENT DEVELOPMENT

FECAL MICROBIOTA TRANSPLANTATION ON METABOLIC PARAMETERS AND METABOLIC DISORDERS Chun-Ying Wu Institute of BioMedical Informatics, National Yang-Ming University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan Metabolic syndrome is a worldwide epidemic problem. Metabolic syndrome is closely related with obesity, cardiovascular diseases, type 2 diabetes, cancer, etc. Among the risk factors contributing to metabolic syndrome, gut microbiota has become an emerging study issue due to its important roles in metabolism and inflammation.

With the advances in high-throughput sequencing technology, many evidence have revealed the relationship between gut microbiota and metabolic syndrome.

Fecal microbiota transplantation (FMT) is the measure to transplant bacterial ecosystem in the fecal material from healthy donors to recipients. In human, FMT has been approved to be very effective in treating recurrent and refractory Clostridium difficile (rCDI), and also

effective in certain inflammatory bowel disease patients. In animal model, FMT is widely used to test hypothesis regarding microbiota and human diseases, including the relationship between gut microbiota and metabolic syndrome.

In 2013, FMT has been shown to transfer obesity from twin pair to mice. In 2016, FMT is reported to be effective in rescuing diet-induced gut microbiota extinction. In 2018, our study demonstrated that FMT transferred the beneficial effect of diet control and exercise to improve metabolic profiles and inflammatory cytokines. In human studies, some preliminary data suggested the potential therapeutic roles of FMT in treating metabolic syndrome. The underlying mechanisms of FMT on metabolic parameters will also be discussed in this lecture.

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2019 TDDW

Symposium (XII) GUT MICROBIOME AND HUMAN DISEASES: CURRENT DEVELOPMENT

IS GUT MICROBIOME ASSOCIATED WITH PANCREATIC DISEASES? Wei-Chih Liao Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Gut microbiota has about 100 times of genes than the human genome has and plays a vital role in the human immune system, which has complicated interactions with nearly all kinds of human diseases. Unlike human genes, which is inherited and consistent, gut microbiota changes with disease status as well as food and drug. Although pancreas does not have its own microbiome, pancreas affects microbiota via endocrine and exocrine function and could be influenced by dysbiosis.

Acute pancreatitis (AP) is the most common pancreatic disease. In acute pancreatitis, disease affects microbiota through several mechanisms.

Lack of antimicrobial pancreatic peptides leads to bacterial translocation and infection. In addition to decreased pancreatic antimicrobial peptide secretion, damage-associated molecular patterns (DAMPs), such as high-mobility group box protein 1 (HMGB1) and heat shock protein 70 (Hsp70), activate the toll-like receptors and induce subsequent activation of NF- kBrelated immune responses as well as changes of intestinal microcirculation/tight junctions. The dysbiosis caused by AP might eventually trigger severe pancreatitis. Recent research showed feeding germ-free (GF) mice with feces from AP mice resulted in more severe disease compared with the control. Collectively, AP and dysbiosis form a vicious cycle during disease progression.

However, probiotics as an intervention failed to

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show significant beneficial effects in patients with severe acute pancreatitis in a meta-analysis, and in one randomized controlled trial (RCT) probiotics treatment resulted in more death and lactate acidosis.

Small intestine bacterial overgrowth (SIBO) is noted in approximately one-third of chronic pancreatitis patients. Dysbiosis with increases in the Firmicutes to Bacteroidetes ratio has been reported. Decrease of certain microorganism in the intestine, for example, Faecalibacterium prausnitzii and Ruminococcus bromii might impact the gut mucosa integrity and endotoxin production, result in impairment of glucose metabolism. Chronic pancreatitis patients have higher endotoxin levels, which is assumed to be attributed to dysbiosis. Moreover, several studies showed specific microbial antigens were related to autoimmune pancreatitis.

Pancreatic cancer is also associated with microbiota. First, type 2 DM and chronic pancreatitis, the risk factors of pancreatic cancer, are related to dysbiosis. Second, the chronic inflammation caused by gut dysbiosis activates proinflammatory pathways inducing STAT3 and NF-kB which have tumorigenic effects.

Microbiome in the oral cavity and pancreatic tumor also play important roles in tumor growth.

Gut microbiota may also affect the efficacy and side effects of chemotherapy and immune therapy.

2019 TDDW

Symposium (XII) GUT MICROBIOME AND HUMAN DISEASES: CURRENT DEVELOPMENT

GUT MICROBIOTA IN PEDIATRIC DISEASES AND HEALTH Yen-Hsuan Ni Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan With the advent of advancing culture-free DNA sequencing and bioinformatics technology, we are now able to understand the gut microbiome plays important roles in the health and disease status. More interestingly, the gut microbiota signature acquired in infancy may predict or incline to the future development of diseases.

The gut microbiota are now expanding their roles in the health and disease status in many fields, including metabolic diseases (diabetes, obesity), cancer (colon cancer and other gastrointestional malignancies), liver diseases (fatty liver, cirrhosis), immunologic diseases (atopic diseases), braingut disorders (irritable bowel syndrome, autism), and so on. There are many factors influencing the constitutions of the gut microbiota, including diet, geography, genetic factors, age, and drugs, particularly antibiotics. Currently, the scientists are exploring the different microbiota signature between the disease and health status and aim to manipulate the gut microbiota signature on the “right” track. Generally speaking, the richness and evenness of the gut microbiota composition are the measures to implicate the healthy and diseased status. The gut is the largest lymphoid organ in our bodies, also the first-line contact

with the environmental antigens and nutrients.

The cross-talk among the microbiota and the immune system and the intestinal epithelium is obviously an intriguing and fascinating issue.

The origin of the bacteria colonizing the neonatal gastrointestinal tract is supposed to be affected by mode of delivery, feeding and maternal conditions.

Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the major bacterial phyla patterns in infancy. The infants’ gut microbiota pattern gradually transit into the adult pattern at about the age of three, when the food intake of the children is similar to that of the adults.

With the advent of next generation sequencing technology and the combination with proteomics and metatranscriptomics, a long-term prospective monitoring on the development of diseases and the evolution of gut microbiota will be very helpful to unravel their critical role in the pathogenesis of many diseases and the gut microbiota may become the therapeutic target. We have already proven an early colonization with R. gnavus in the gut promoted allergic disease in infants. This will help initiate our investigations about the roles of gut microbiota in children health and diseases.

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2019 TDDW

Symposium (XII) GUT MICROBIOME AND HUMAN DISEASES: CURRENT DEVELOPMENT

GUT MICROBIOTA AND CIRRHOSIS COMPLICATIONS: PREDICTION, PROGNOSIS, AND TREATMENT Sen-Yung Hsieh Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Cirrhosis is a result of advanced liver disease characterized by replacement of liver tissue by extensive fibrosis (scar tissue), progressive loss of normal liver functions, and finally disruption of homeostasis of many body systems and organs.

The gut microbiome is estimated to be about ten times more microbial cells than our own cells of our body. As the liver receives its blood supply mainly from the gut, gut microbiome and liver directly (such as by microbial metabolites) and indirectly (via modulating host immune responses) intimately linked. Cumulating evidence shows the significance of gut microbiota

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and the impact of changes in their constituents in human health and diseases (“dysbiosis”), particularly cirrhosis. Gut dysbiosis is known to be associated with cirrhosis complications, such as hepatic encephalopathy. Profiling the changes in gut microbiome can be applied to the prediction of clinical outcomes of patients with decompensated cirrhosis. Moreover, recent studies suggest that by manipulating the gut microbiome with fecal microbiota transplantation, we will be able to treat and prevent from recurrence of hepatic encephalopathy in patients of decompensated cirrhosis soon.

2019 TDDW

Symposium (XIII) RECENT PROGRESS IN UNDERSTANDING AND MANAGEMENT OF GIST

CLINICAL DIAGNOSIS OF GASTROINTESTINAL STROMAL TUMOR (GIST): FROM THE MOLECULAR GENETIC POINT OF VIEW Chiao-En Wu Division of Medical Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Gastrointestinal stromal tumors (GISTs) originating from the interstitial cells of Cajal are mesenchymal tumors of the gastrointestinal tract and have been found to harbor c-KIT mutations and KIT (CD117) expression since 1998. Later, PDGFRA mutations, SDH alterations, and other drive mutations were identified in GISTs. In addition, more and more protein markers such as DOG1, PKCθ were found to be expressed in GISTs which might help clinicians diagnose CD117-negative GISTs. Therefore, I will comprehensively review the molecular markers and genetics of GISTs and provide clinicians useful information in diagnostic and therapeutic strategies of GISTs. Twenty years

after the discovery of KIT in GISTs, the diagnosis of GISTs became much more accurate by using immunohistochemical (IHC) panel (CD117/DOG1) and molecular analysis (KIT/PDGFRA), both of which constitute the gold standard of diagnosis in GISTs. The accurately molecular diagnosis of GISTs guides clinicians to precision medicine and provides optimal treatment for the patients with GISTs. Successful treatment in GISTs prolongs the survival of GIST patients and causes GISTs to become a chronic disease. In the future, the development of effective treatment for GISTs resistant to imatinib/sunitinib/regorafenib and KIT/ PDGFRA-WT GISTs will be the challenge for GISTs.

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2019 TDDW

Symposium (XIII) RECENT PROGRESS IN UNDERSTANDING AND MANAGEMENT OF GIST

THE ROLE AND MAIN CONCERNS OF SURGERY FOR METASTATIC GIST IN THE ERA OF THE TARGETED THERAPY Shang-Yu Wang General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan After the discovery of disease-causing gene, KIT, of gastrointestinal stromal tumor (GIST) in 1998, introduction of targeted therapy, tyrosine kinase inhibitor (TKI), as a treatment modality for GIST followed soon in 2002. This breakthrough has changed the strategy of GIST treatment revolutionarily. The overall survival of GIST has been markedly improved from a median of 19 months in pre-imatinib era to 57 months in postimatinib era. Although removal of primary tumor, especially for single tumor disease, is the golden standard of treatment, optimal outcome cannot be achieved without TKI. Currently, the TKI can be administrated as adjuvant, palliative, or neoadjuvant therapy.

Combined with surgery, either curative or cytoreductive, evidence is being accumulated to support variable practice strategies to improve prognosis. However, the impact of TKI

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on surgery has been proposed and reports of surgery after TKI treatment revealed relatively high postoperative complication. Therefore, we still have several issues, including how to select patients under TKI for surgery, indications of surgery for these patients, preoperative preparation for these patients, and postoperative care, to tackle with. In addition, the role of surgery should be clearly deďŹ ned due to increasing choice of TKI instead of imatinib.

Metastatic disease no doubt would be treated with TKI. Surgical treatment, under this scenario, is usually cytoreductive surgery. Adjunct with TKI, we will discuss how to select appropriate patients for cytoreductive surgery, how to prepare these patients to undergo surgery, the impact of TKI on surgery, and the latest evidence of cytoreductive surgery for metastatic disease.

2019 TDDW

Symposium (XIII) RECENT PROGRESS IN UNDERSTANDING AND MANAGEMENT OF GIST

THE IMPACT OF MUTATION ANALYSIS IN MANAGEMENT OF GIST AND FUTURE INSPIRATION Yan-Shen Shan Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor derived from the interstitial Cells of Cajal (ICCs) in whole sites of the gastrointestinal tracts. Gain-of-function mutation of c-kit gene induces constitutive tyrosine protein phosphorylation of a KIT tyrosine kinase receptor, is observed in the majority of GIST patients. Kinds of kit exons mutation and PDGFR mutations are found in pathology. Mutation in exon 11 of the c-kit gene is observed in 50–80% of malignant GIST. The mutation analysis also confirms the presence of other exons (usually exon 9, 13 or 17) in the considerable number of GIST patients.

Based on the pathogenesis of kit mutation in GISTs, those mutations are not only as prognostic markers but also as treatment markers for choosing drug. The first line target therapy make great efficacy in metastatic/advanced GISTs, but the different mutation site also shows resistance

to it, and confers to the 2 nd or 3 rd line drug.

However, there exists GIST patients reluctant to those target therapy, exploration the reason for the resistance is necessary to develop new treatment. In our recent study, we find that exon 11 codons 557-558 mutation is the most common mutation site. In these GISTs, they frequently develop liver metastasis because codons 557558 mutation will increase expression of CXCR4 via ETV1 to promote cancer cells migration to liver. At the same time, it also increase the autophagy activity in the GIST cells, which further increase cell growth and resistance to imatinib treatment. After added chloroquinon (CQ) to inhibit autophagy activity, the efficacy of imatinib will be improved in vitro and in vivo. In conclusion, our findings highlight the importance of mutation analysis in clinical treatment and in development of potential therapeutic targets for metastatic GISTs in the future.

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2019 TDDW

Symposium (XIII) RECENT PROGRESS IN UNDERSTANDING AND MANAGEMENT OF GIST

RECENT DEVELOPMENT OF NEW AGENTS IN GIST Chueh-Chuan Yen Division of Medical Oncology, Center for Immuno-oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor in Taiwan, account for around 30% of all sarcomas.

The majority of GISTs contain mutations in the gene encoding the KIT tyrosine kinase receptor; however, but <10% have mutations in the gene encoding platelet-derived growth factor receptor A (PDGFRA) as the oncogenic driving force.

Tyrosine kinase inhibitor (TKI) imatinib is the standard first-line therapy and can achieve a median overall survival (OS) rate of 5-6 years in patients with advanced disease. However, disease progression, which most likely occurs due to the development of secondary mutations, is expected within 2 to 3 years of imatinib therapy.

Therapeutic options are limited for these patients, with sunitinib maleate as the standard second-line agent, and regorafenib as third-line therapy.

Several other TKIs, such as sorafenib, nilotinib, pazopanib, masitinib, had been explored their efficacy in GIST treatment, but with limited success. Recently, Avapritinib (BLU-285), a highly selective and potent a type I KIT/PDGFRα inhibitor that binds to the active protein kinase

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conformation, with biochemical activity against a wide range of primary and secondary mutations in the nanomolar range. In the ≥fourth-line setting, overall response rate (ORR) was 20% with a median duration of response (DOR) of over 7 months. In patients with GISTs with a PDGFRA D842V mutation, avapritinib caused tumor shrinkage in 98% of the cases, with an ORR of 84%.

Ripretinib (DCC-2618), a switch-control type II inhibitor of KIT, which arrests KIT in an inactive state, inhibiting the full spectrum of the mutations known to be present in patients with GISTs in exons 9, 11, 13, 14, 17, and 18, as well as an inhibitor of PDGFRα carrying exon 18 mutations, including the D842V mutation. In the ≥fourth-line setting, ORR, disease control rate (DCR) were respectively of 9% and 66%, with a progressionfree survival of 24 weeks.

In this talk, these as well as some other new TKIs will be reviewed. The potential of checkpoint inhibitors in GIST treatment will also be discussed.

2019 TDDW

Symposium (XIV) UPDATE OF NEUROENDOCRINE TUMORS

GA-68 DOTATOC AND F-18 FDG PET/CT FOR IDENTIFYING PRIMARY LESIONS OF SUSPECTED AND METASTATIC NET Shih-Hsin Chen Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan To investigate the diagnostic accuracy of 68Ga-DOTATOC and 18F-FDG PET/CT to identify the primary foci in Taiwanese patients with clinically suspected neuroendocrine tumors (NET) and NET of unknown primary site, patients with clinically suspected NET and NET of unknown primary site were recruited. All participants underwent a conventional workup (including CT, MR, endoscopic ultrasound), 68Ga-DOTATOC, and 18F-FDG PET/CT. The results of pathology and findings on clinical follow-up served as the gold standard. Among the 36 patients included in the study, we were able to identify the primary tumor in 17 participants (47.2%). The overall sensitivity values of 68Ga-DOTATOC, 18F-FDG,

and conventional workup were 88%, 41%, and 53%, respectively, whereas the specificities were 100%, 100%, 68%, respectively. The areas under curve of 68Ga-DOTATOC, 18F-FDG, and conventional workup were 0.941, 0.706, and 0.607, respectively. 68Ga-DOTATOC was more sensitive than 18F-FDG and more specific than conventional workup. Treatment changes as a result of 68Ga-DOTATOC PET/CT findings occurred in 12 (33.3%) of the 36 study participants. Our data confirmed the usefulness of 68Ga-DOTATOC in the identification of NET. In addition, treatment modifications as a result of 68Ga-DOTATOC PET/CT findings were evident in approximately one third of NET patients.

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2019 TDDW

Symposium (XIV) UPDATE OF NEUROENDOCRINE TUMORS

SURVIVAL TREATMENT OF NEUROENDOCRINE TUMORS Tsann-Long Hwang Department of Surgery, LinKou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan Surgery is the mainstay for treatment of local or locoregional GEP-NETs. Patients with pNETs that are symptomatic, intermediateto-high grade, or measure greater than 2 cm should undergo formal oncologic surgery, such as Whipple resection or distal pancreatectomy/ splenectomy. Enucleation represents an alternative option for small, localized pancreatic NETs but may lack oncologic adequacy in terms of lymphadenectomy and clearance of resection margins. The management of small (<2 cm), low-grade, nonfunctioning, incidentally detected pNETs is currently controversial. The surgical approach for midgut NETs primarily depends on tumor location. Partial small bowel resections are usually performed for jejunal or proximal ileal tumors, whereas right hemicolectomy is indicated for tumors arising in or near the ileocecal valve.

one patient was noted to have liver metastasis at diagnosis. Kaplan-Meier method was used for survival analysis. Among the 60 patients, 28 patients had non-functional neuroendocrine tumor (islet cell tumor), 3 patients had neuroendocrine carcinoma (islet cell carcinoma), 25 patients had insulinoma, 7 had glucagonoma, 3 had somatostatinoma, and 1 had gastrinoma. Median tumor size is 1.5cm. Some of them had multiple histological functional presentation. Non-functional pancreatic neuroendocrine tumor accounted for 31 patients (52%) and functional pancreatic neuroendocrine tumor accounted for 29 patients (48%). Operative records were also reviewed.

Overall survival for all 60 patients was 245.6 months. In category, overall survival was 266.4 months and 89.9 months for functional group and non-functional group respectively (p=0.115).

We retrospectively collected 60 patients with small size (<2cm) neuroendocrine tumor in Chang Gung Memorial Hospital from September 1992 to November 2014. All 60 patients received surgical resection and were pathologically proved pancreatic neuroendocrine tumor. Only

Small size neuroendocrine tumor had favorable surgical outcome. Patients with functional neuroendocrine tumor had longer overall survival time than patients with nonfunctional neuroendocrine tumor.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

LONG-TERM EFFECT OF HELICOBACTER PYLORI ERADICATION, BENEFITS BEYOND GASTRIC CANCER PREVENTION Chieh-Chang Chen Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Helicobacter pylori (H. pylori) is a highly prevalent pathogen, which infects more than half of the populations worldwide. H. pylori infection is one of the major risk factors for GC development.

H. pylori is classified by the International Agency for Research on Cancer of the World Health Organization as class I human carcinogen. H. pylori eradication can reduce or even eliminate gastric mucosal inflammation and reverse the H. pylori-associated molecular events. Beyond gastric cancer, H. pylori links to various other conditions, such as peptic ulcer disease, obesity, metabolic syndrome and colon neoplasms. We will discuss the benefit of H. pylori eradication in this talk.

Studies have shown eradication therapy was superior to ulcer healing drug both in gastric ulcer and duodenal ulcer healing. In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment. Study on H. pylori eradication for peptic ulcer primary prophylaxis in the general population is lacking except for patients with ulcer-like functional dyspepsia and naïve nonsteroidal anti-inflammatory drug (NSAID) users. According to data from randomized intervention trials, naive NSAID users certainly benefit from H. pylori eradication therapy prior to the initiation of NSAID. In patients with ‘ulcer-like’ functional dyspepsia, Hsu et al. reported that eradication of H. pylori can prevent the subsequent development of peptic ulcers in a double-blind, placebo-controlled trial followed

for one year in Taiwan. The mass eradication program in Matzu island showed 67.4% reduction in peptic ulcer disease.

The associations between H. pylori infection and metabolic disease are believed to involve modulation of blood glucose, lipoproteins, and inflammatory markers. A meta-analysis revealed H. pylori infection is positively associated with MS. Infection with H. pylori is also associated with higher triglyceride, fasting glucose, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), systolic blood pressure and lower highdensity lipoprotein cholesterol (HDL-C). Our study showed there were mild increase in body weight and high density lipoprotein and decrease in the insulin resistance. There were no significant changes in the prevalence of metabolic syndrome at week 8 and 1 year, after H. pylori eradication. The results were compatible with study from Gen et al, but were against studies from Park et al and Ando et al. Further studies were needed to clarify this issue.

Helicobacter pylori infection is associated with colorectal adenoma and confers a 1.3- to 2.26-fold increased risk. A retrospective cohort study showed patients with persistent H. pylori infection exhibited a higher risk of colorectal adenoma than the patients underwent H. pylori eradication. Further study for the mechanistic model is indicated.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

GASTRIC CANCER AFTER H. PYLORI ERADICATION THERAPY IN JAPAN Masanori Ito Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan Helicobacter pylori (H. pylori) infection is strongly associated with the incidence of gastric cancer. A prospective study in Japan has shown that H. pylori eradication therapy reduces the incidence of metachronous gastric cancer. In 2013, the Japanese national health insurance system achieved the distinction of being the first globally to cover H. pylori eradication therapy for chronic gastritis. Therefore, an increasing number of Japanese patients are receiving eradication therapy aimed at prevention of gastric cancer.

However, some patients developed clinically diagnosed gastric cancer even after successful eradication. We previously reported the difficulty of detecting these tumors endoscopically because of their characteristic features, including the presence of epithelium with low-grade atypia (ELA) on the surface of the gastric cancer tissue (Ito et al. AP&T 2005, Kitamura et al. Helicobacter

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2014). Recently, we investigated the origin of ELA by deep target-sequencing, and found that ELA originates from cancer after re-differentiation (Masuda et al. J Gastroenterol 2019).

In addition, we reported that H. pylori eradication therapy increased the prevalence of differentiated-type gastric cancer with submucosal invasion despite patients’ completion of annual endoscopic screening after eradication (Hata K et al. Digestion 2019). Therefore, early detection of gastric cancer in patient after eradication is quite important in recent clinical practice. We focused on reddish depressed lesions (RDLs) in patients who had undergone successful eradication therapy. Magnifying narrow band imaging demonstrated significantly superior diagnostic efficacy with respect to RDL (Kotachi T, et al.

Digestion 2018).

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

LONG-TERM EFFECTS OF H. PYLORI ERADICATION ON THE TUMOR MCIROENVIRONMENT Nayoung Kim Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Seoul, Korea Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea Helicobacter pylori (HP) is the strongest risk factor for gastric cancer (GC) and there have been accumulated data regarding chemoprevention effect of HP eradication. As tumor microenvironment is required for tumor initiation, progression, and metastasis in terms of interaction among gastrointestinal (GI) epithelial, stromal, and immune cells HP eradication might affect this tumor microenvironment. The immune response determines the progression of gastric atrophy, metaplasia, and dysplasia, because Th1 cells produce specific cytokines such as interleukin (IL)-1 in response to infection with HP. Tight junction protein is one of the important components of epithelial microenvironment. In addition, mesenchymal stem cells (MSCs) are a minor population of multipotent, nonhematopoietic cells in the bone marrow that are actively recruited to the sites of inflammation and injury. A significant portion of cancer-associated fibroblasts (CAFs) was found to originate from the bone marrow–derived MSCs44 and contribute to the normal bone marrow MSC niche and to selfrenewal of MSCs. These bone marrow niche cells are expanded in a transforming growth factor-β1 (TGFβ)-dependent manner and recruited through CXCR4 and CXCL12 signaling, together with MSCs, to incipient tumors, where they appear as CAFs. Crypt base columnar cells are fast-cycling stem cells that express Lgr5 and CD133 (Prom-

1). From this background TGF-β1-induced epithelial-mesenchymal transition (EMT) markers and GC stem cells such as CD44v8-10 mRNA and Lgr5 were investigated to evaluate the tumor microenvironment after HP eradication. One-year follow-up after HP eradication showed inhibition of TGF-β1-induced EMT and CD44v8-10 mRNA and Lgr5 pathways. mRNA expression of IL1B decreased in the body of cancer/dysplasia group. In addition, tight junction protein gene such as zonula occludense 1 (zo-1) showed different expression depending on HP infection and it changed after HP eradication. Taken together HP eradication might improve the tumor microenvrionment in term of EMT, stem cell, tight junction protein and IL-1B which contribute to prevention of gastric carcinogenesis.

Keywords: tumor, microenvrionment, Helicobacter pylori, gastric cancer, eradication, transforming growth factor-β1

References: 1. Quante M, Varga J, Wang TC, Greten FR. The gastrointestinal tumor microenvironment.

Gastroenterology 2013;145:63–78.

2. Kim N. Chemoprevention of gastric cancer

by Helicobacter pylori eradication and its underlying mechanism. J Gastroenterol Hepatol. 2019;34:1287-1295.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

A TWO-STAGE SCREENING PROGRAM FOR GASTRIC CANCER PREVENTION: A COMMUNITY-BASED STUDY Tsung-Hsien Chiang Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Carcinogenesis of gastric cancer follows a multistage process that develops from chronic active gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and finally to carcinoma.

The traditional approach for prevention of gastric cancer is secondary prevention and emphasizes the use of endoscopy to identify early cancer and provide curative treatment. As treatment of gastric cancer at the symptomatic stage represents a significant medical burden, clinicians have been encouraged to focus on designing preventive strategies instead of multimodal therapies.

Because Helicobacter pylori is recognized as the main risk factor to promote gastric carcinogenesis through multiple mechanism by causing chronic gastric inflammation, primary prevention of gastric cancer could be achievable through H. pylori eradication. Matsu Islands is an archipelago of

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five major islands in the Taiwan Strait; the annual incidence rate of gastric cancer is three times than Taiwan main island. Because of the limitation of medical resources and high incidence of gastric cancer in Matsu Islands, it provides an opportunity to implement a screen-and-treat procedure for H. pylori infection. Up to now, there are six rounds of mass eradication (from 2004 to 2018), and the H. pylori infection rate in this population steadily declines from 63% at 2004 to 10% in 2016. The estimated reduction of gastric cancer is 25% in 2008 and 47% in 2015, and the annual incidence rate would continue to decline at the same rate of Taiwan main island. At the population level, mass screening and treatment of H. pylori infection could achieve the prevention of gastric cancer, especially for high incidence region.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

LONG-TERM OUTCOMES OF ENDOSCOPIC RESECTION AND METACHRONOUS CANCER AFTER ENDOSCOPIC RESECTION FOR ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION IN JAPAN Seiichiro Abe Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan Background and Aim: Endoscopic resection (ER) of superficial adenocarcinoma of the esophagogastric junction (AEJG) has been shown to be safe and effective. However, long-term data in patients undergoing ER for superficial AEGJ in Japan is still limited. The aim of this study was to determine the effect of ER on survival and occurrence of metachronous cancer of patients with superficial EA. Methods: A retrospective analysis of patients who underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for superficial EA in 13 centers in Japan was performed. The patients were classified in either low-risk or high-risk for lymph node metastasis based on histological features. Patient at low risk for metastasis were defined as A) those with a mucosal cancer without both LVI and a poorly-differentiated component, or B) those with a cancer with submucosal depth ≤500 µm without LVI, without a poorly-differentiated component, and measuring ≤30 mm. High risk patients were all patients with mucosal and submucosal AEGJ who did not meet the low risk criteria (Ishihara R, et al. J Gastroenterol. 2017). The incidence of

metachronous EA as well as, overall survival (OS) and disease-specific survival (DSS) rate were calculated.

Results: A total of 372 patients who underwent ER were included. A total of 277 patients were low-risk and 95 were high-risk for lymph node metastasis. Five-year cumulative incidences of local recurrence were 13% and 0.5% in the EMR and ESD group, respectively (p<0.01). A total of 6 deaths were observed in the high risk group and none in the low risk group.

The 5-year OS rates in the low-risk group, the high-risk group with additional treatment, and the high-risk group without additional treatment were 93.9%, 77.7%, and 81.6%, respectively. The 5-year DSS rates in the three groups were 100%, 94.4%, and 92.8%, respectively. The 5-year cumulative incidence of metachronous EA in 316 patients without additional treatment was 1.1%.

Conclusions: Favorable long-term outcomes with ER were observed in patients with AEGJ who met the low-risk criteria for lymph node metastasis. ESD was reasonable and effective treatment in Japanese patients.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW LONG-TERM EFFECTS OF HELICOBACTER PYLORI ERADICATION IN THE ASIAPACIFIC REGION: OTHER BENEFITS OR CONCERNS?

NOVEL RISK STRATIFICATION FOR METACHRONOUS RECURRENCE AFTER CURATIVE ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER Hyo-Joon Yang Division of Gastroenterology, Department of Internal Medicine and Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea Background and aims: This study stratified the risk of developing metachronous gastric cancer (MGC) after curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) to enable the customization of endoscopic surveillance for MGC. Methods: A total of 1115 patients who underwent curative ESD based on the expanded criteria for differentiated EGC from 2005 to 2014 at a single tertiary hospital were enrolled in this retrospective cohort study. They were followed up with annual endoscopy for a median of 50.1 months. H. pylori and histologic intestinal metaplasia (IM) were evaluated. The KaplanMeier method and Cox regression analysis were used for risk stratification.

Results: Three risk groups were identified: group 1 comprised patients with a synchronous

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neoplasm; group 2 comprised male patients with corpus IM; and group 3 comprised male patients without corpus IM or female patients. The 5and 7-year cumulative risks for metachronous recurrence were 15.1% and 26.1%, respectively, in group 1; 5.2% and 9.3%, respectively, in group 2; and 3.8% and 4.9%, respectively, in group 3 (P <0.001 by log-rank test). The incidence of MGCs showed constant linear increase in groups 1 and 2, even after five years, while it plateaued after five years in group 3. H. pylori infection or eradication status was not associated with metachronous recurrence.

Conclusions: Meticulous annual endoscopic surveillance for MGC for more than five years is strongly recommended for patients with synchronous neoplasm. Endoscopic surveillance could also be extended beyond five years in male patients with corpus IM.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW AUTOIMMUNE PANCREATITIS: CURRENT DIAGNOSIS & MANAGEMENT IN THE ASIA-PACIFIC REGION

AUTOIMMUNE PANCREATITIS IN JAPAN Atsushi Masamune Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan Objectives: Autoimmune pancreatitis (AIP) is a pancreatic manifestation of systemic IgG4related diseases. We conducted nationwide epidemiological survey to clarify the clinicoepidemiological features of AIP in Japan.

Methods: We surveyed AIP patients who had visited the selected hospitals in 2016. AIP was diagnosed according to the clinical diagnostic criteria for AIP proposed by the Japan Pancreas Society in 2011. This study consisted of two stage surveys; the first survey estimated the number of patients with AIP and the second survey assessed their clinical features.

Results: By the end of March 2018, 854 departments responded online to the first stage survey (response rate: 34.1%). The estimated total number of AIP patients in 2016 was 13,440 representing 2.3-fold increases compared to that in the 2011 survey. The estimated number

of newly diagnosed AIP patients was 3,980, with an annual incidence rate of 3.1 per 100,000 persons. We obtained detailed clinical information of 1,474 patients in the second survey. Male to female ratio was 2.96:1. The mean age was 68.0 and the mean age at disease onset was 64.8.

About 2/3 of the patients were symptomatic, and jaundice was the leading reason to visit hospitals.

Extra-pancreatic lesions developed in 873/1,449 (60.2%) cases; sclerosing cholangitis accounted for 69.0% and lacrimal glands/sialadenitis did 33.3% cases. Pancreatic tissues were obtained in 64.0% cases, mainly (84.0%) by EUS-guided fine needle aspiration. Eighty-five % patients received steroid therapy, which was effective in almost all cases. Malignant tumor developed synchronously in 47 cases.

Conclusions: We clarified the current status of AIP in Japan.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW AUTOIMMUNE PANCREATITIS: CURRENT DIAGNOSIS & MANAGEMENT IN THE ASIA-PACIFIC REGION

TYPE 2 AUTOIMMUNE PANCREATITIS IN ASIA Tae Jun Song Division of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Autoimmune pancreatitis (AIP) consists of two distinct clinical and histopathological. Type 1 AIP refers to the subtype that has the histological pattern known as lymphoplasmacytic sclerosing pancreatitis (LPSP) or granulocytic epithelial lesion (GEL)-negative AIP, whereas type 2 AIP refers to the subtype that has the histological pattern called idiopathic duct-centric pancreatitis (IDCP) or GEL-positive AIP.1 Type 1 AIP is considered as part of the spectrum of IgG4-related systemic disease, whereas type 2 disease is not. Characteristic clinical, serologic, and histopathologic features distinguish the two subtypes of the disease, although some overlap exists. 1 Different diagnostic criteria and algorithms are applied in the diagnosis of AIP, depending on the subtype of AIP.2 Type 2 AIP appears to be relatively common in the United States and Europe but rare in Asia.

Type 2 AIP has been reported to be very rare in Japan, but it accounted for 37% of cases of resected AIP from the United States and 45% in Europe.3,4 Until now, prevalence rates of type 2 AIP in the West vary widely (12.9% to 45%) in the literature.5 According to the Japanese nationwide survey, 2.8% of cases of histologically confirmed type 2 AIP were reported. In Korea, type 2 AIP

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was not so rare as previously thought, with an estimated 10% prevalence rate among total AIP.1 Since the definitive diagnosis of type 2 AIP requires pancreatic histology, under-recognition of type 2 AIP is far more likely than that of type 1 AIP. This might suggest that type 2 AIP has been overlooked for many years in East Asia since the histological diagnostic criteria of type 2 AIP was originally established in the West based on histological findings of surgically resected pancreas specimens from patients with nonalcoholic mass-forming pancreatitis and Asian pathologists were not familiar with characteristic h i s t o l o g y o f I D C P. 5 D i ff e r e n t d i a g n o s t i c approaches in East Asia may also contribute to the relatively lower prevalence rate of type 2 AIP. In South Korea and Japan, diagnostic ERP and a subsequent diagnostic steroid trial have been more actively used in patients with suspected AIP than in the West; type 2 AIP cases can therefore be mistakenly classified as simply AIP or AIPNOS (in the absence of diagnostic histology) because pancreatic imaging findings are identical between type 1 and type 2 AIP and both subtypes well respond to steroids.

The relapse rate of type 2 AIP is generally considered to be significantly lower than in type 1 AIP.1 Due to the lower relapse rates in type 2 AIP, long-term maintenance therapy may not be

2019 TDDW necessary. In our study, the relapse rate of type 2 AIP was about 8%.5 In a study from the Mayo Clinic, the cumulative relapse rate was 10.6% at 3 years (median follow-up, 2.9 years).6 In a recent European study, however, the relapse of type 2 AIP was 34%.7 The authors suggested that longer follow-up period (>5 years) and fewer pancreatic surgery procedures was attributable to the high relapse rate.

In conclusion, type 2 AIP is rare but clinically relevant in South Korea. Gastroenterologists should have a high index of clinical suspicion for type 2 AIP in young patients with ulcerative colitis who present with clinical acute pancreatitis of uncertain etiology. EďŹ&#x20AC;orts to increase the amount of pancreatic tissue obtained by EUS-guided core biopsy are also required. As our knowledge and experience of type 2 AIP has accumulated, diagnostic ability will increase.

References: 1.

2.

Song TJ, Kim JH, Kim MH, et al. Comparison of clinical findings between histologically confirmed type 1 and type 2 autoimmune pancreatitis. J Gastroenterol Hepatol 2012;27:700-8.

Shimosegawa T, Chari ST, Frulloni L, et al.

International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the

International Association of Pancreatology.

Pancreas 2011;40:352-8.

3.

Zamboni G, Luttges J, Capelli P, et al.

Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 b i o p s y s p e c i m e n s . Vi r c h o w s A r c h 2004;445:552-63.

4.

Notohara K, Burgart LJ, Yadav D, et al. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol 2003;27:1119-27.

5.

Oh D, Song TJ, Moon SH, et al. Type 2 Autoimmune Pancreatitis (Idiopathic DuctCentric Pancreatitis) Highlighting Patients Presenting as Clinical Acute Pancreatitis: A Single-Center Experience. Gut Liver 2019;13:461-70.

6.

Hart PA, Levy MJ, Smyrk TC, et al. Clinical profiles and outcomes in idiopathic ductcentric chronic pancreatitis (type 2 autoimmune pancreatitis): the Mayo Clinic experience. Gut 2016;65:1702-9.

7.

Lorenzo D, Maire F, Stefanescu C, et al.

Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2018;16:59-67.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW AUTOIMMUNE PANCREATITIS: CURRENT DIAGNOSIS & MANAGEMENT IN THE ASIA-PACIFIC REGION

URINARY TRYPSINOGEN-2 LEVEL PREDICTS LOCAL COMPLICATIONS OF ACUTE PANCREATITIS Hsing-Chien Wu Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan The mortality of acute pancreatitis decreased significantly in recent decades from 10% to less than 2%. However, local complications of acute pancreatitis (AP) carry risks of morbidity/ mortality. This study aimed to assess whether urinary trypsinogen-2 levels and Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission predicted subsequent local complications.

One hundred and forty-four consecutive patients with AP were prospectively followed till 6 months after discharge. Urinary trypsinogen-2 levels were measured within 24 hours of admission. Local complications (acute peripancreatic fluid collection, acute necrotic collection, pseudocyst, walled-off necrosis) were diagnosed by abdominal CT. Cutoff for trypsinogen-2 level was assessed using receiver operating characteristic (ROC) curve, and predictors of local complications were analyzed by logistic regression.

Thirty-seven (25.7%) patients developed local complications. Urinary trypsinogen-2 levels were significantly higher in patients with local complications compared with those without local complications [median (interquartile range <IQR>), 3210 (620-9764.4) µg/L vs 627.3 (72.3-

72

5895) µg/L, P = 0.006]. Urinary trypsinogen-2 significantly outperformed BISAP score in predicting local complications [area under the ROC curve 0.65 (95% CI: 0.55-0.75) vs 0.48 (95% CI: 0.38-0.58), P = 0.005]. At the optimal cutoff of 500 µg/L, the sensitivity, specificity, positive predictive value and negative predictive value of trypsinogen-2 level were 78.4%, 45.8%, 33.3%, and 86.0%, respectively. Urinary trypsinogen-2 level >500 µg/L was an independent predictor of local complications [adjusted odds ratio (OR), 3.72; 95% CI: 1.42-9.76; P = 0.007]. By contrast, BISAP score ≥3 and pleural effusion predicted organ failure but not local complications.

In a prospective cohort, urinary trypsinogen-2 level >500 µg/L independently predicted local complications of AP. Urinary trypsinogen-2 level is a useful commercialized tool to diagnose acute pancreatitis and has also been tested for severity prediction before publication of revised Atlanta Classification. In our study, trypsinogen-2 level independently predicted local complications (mostly peripancreatic fluid collection) better than it did for organ failure. Our study also implied that low urinary trypsinogen-2 level has potential to exclude moderately severe and severe acute pancreatitis.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW AUTOIMMUNE PANCREATITIS: CURRENT DIAGNOSIS & MANAGEMENT IN THE ASIA-PACIFIC REGION

IDENTIFYING A NEW ANTIGEN OF AUTOIMMUNE PANCREATITIS Masahiro Shiokawa Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan Objective: The pathogenic roles of IgG in patients with autoimmune pancreatitis (AIP) remained unknown. And if the IgG has pathogenic roles, the antigen has been unclear.

Method: We examined the pathogenic activity of circulating IgG in patients with AIP by injecting their IgGs into neonatal Balb/c mice. Next, to identify the autoantigen, pancreatic ECM proteins were screened by enzyme-linked immunosorbent assay with sera obtained from 10 AIP patients and 10 controls. The candidate protein was validated with sera from another cohort of 41 AIP patients and 102 controls. Colocalization of AIP-patient IgG with the candidate autoantigen was examined in the pancreas of AIP patients and mice injected with AIP-patient IgGs. Mice were immunized with the candidate autoantigen to examine its

pathogenicity.

Results: Subcutaneous injection of patients’ IgG, but not control IgG, resulted in pancreatic injuries. Next, we identified a laminin 511 protein as an autoantigen. Combined with the validation group, 26/51 (51.0%) AIP patients and 2/112 (1.8%) controls were positive for laminin 511 antibodies. IgG of AIP patients with laminin 511 antibodies was colocalized with laminin 511 in the pancreatic ECM of AIP patients, and in mouse pancreas. Immunization with laminin 511 protein induced pancreatic injury in mice, fulfilling the pathologic criteria for human AIP. AIP patients with X antibodies exhibited distinctive clinical features.

Conclusions: Our findings indicate that laminin 511 is a primary antigen for AIP.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW AUTOIMMUNE PANCREATITIS: CURRENT DIAGNOSIS & MANAGEMENT IN THE ASIA-PACIFIC REGION

PERSPECTIVES ON CLINICAL APPLICATIONS OF CTCS IN PATIENTS WITH PANCREATIC CANCER Dong Uk Kim Department of Gastroenterology, Pusan National University Hospital, Busan, Koera The overwhelming majority of pancreatic cancer patients present with advanced disease, and their tumor tissues are rarely sampled, beyond the minimal amounts of fixed cells required to render a cancer diagnosis. As a result, an opportunity to generate living “personalized” models from each patient’s tumor, in order to perform more sophisticated molecular analyses and drug sensitivity testing, is almost always missed. It is important to develop an innovative pipeline for characterizing a patient’s pancreatic cancer without the need for obtaining tissue biopsies and facilitating the isolation of live pancreatic cancer cells released from the tumor into the blood circulation (“circulating tumor cells” or CTCs). The CTCs can then be expanded in vitro as an immortalized model of their cancer, and utilized as a representative of tumor heterogeneity for a variety of treatment decisionmaking and disease monitoring approaches.

Importantly, this liquid biopsy requires no more than a single tube of blood, which can be obtained during a routine blood draw at each re-staging.

A device has been engineered which readily yields live pancreatic cancer cells when isolating CTCs from the blood of cancer patients. Serial blood samples, which are obtained peripherally in the surgical and metastatic patients, determine

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whether re-appearance or evolution of CTCs (single or clusters) precedes disease recurrence or progression visible on imaging. Another innovative aspect of CTCs study is to identify molecular abnormalities in single CTCs, which provide unprecedented insights into how these abnormalities impact disease outcome in the patient, and the responses to therapy. I suggest the development of the practical framework for clinical implementation of a CTC platform in pancreatic cancer patients, with direct implications for diagnosis and therapy.

References: 1.

Cayrefourcq, L., et al. Establishment and characterization of a cell line from human circulating colon cancer cells. Cancer Res. 2015;75:892-901.

2.

Maheswaran, S. and D.A. Haber. Ex Vivo Culture of CTCs: An Emerging Resource to Guide Cancer Therapy. Cancer Res. 2015;75:2411-5.

3.

Lapin M, Tjensvoll K, Oltedal S, et al. Singlecell mRNA profiling reveals transcriptional heterogeneity among pancreatic circulating tumour cells. BMC Cancer. 2017 May 31;17(1):390.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

SYSTEMIC APPROACH TO REDUCE PORT-COLONOSCOPY COLORECTAL CANCER WITHIN AN ORGANIZED SCREENING PROGRAM Li-Chun Chang Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Population screening with fecal immunochemical testing (FIT) can effectively reduce mortality from CRC. Nevertheless, interval cancers (ICs) still occur between screening rounds, either after negative fecal testing or after colonoscopy. Previous studies have shown that ICs after colonoscopy result primarily from lesions missed at colonoscopy and, less often, from biological factors, such as rapidly growing neoplasms. Therefore, the identification of potential risk factors for the occurrence of ICs through monitoring the screening program is essential. ICs have been demonstrated closely associated with the quality of colonoscopy and may affect the effectiveness of the entire screening program. Adenoma detection rate (ADR) is one of the most important indicators that are closely associated with subsequent risk of IC or even CRC death.

Quantitative FIT permits the determination of an optimal cut-off for the fecal hemoglobin concentration (FHbC) based on the regional prevalence of CRCs and the available capacity of colonoscopy. The quantitative measurement of FHbC has been described but is seldom

used clinically. It has been reported that FHbC determines a priori chance of an advanced lesion and correlates with the histological severity of colorectal neoplasms detected at colonoscopy.

Recent studies have demonstrated that FHbC, even when below the determined cut-off, is associated with the subsequent risk of incident neoplasm. Since missed neoplasms are the primary cause of IC, it is reasonable to speculate that higher levels of FHbC carry a higher risk of IC after colonoscopy and thereby we can apply it for identification of people at risk of IC under the current quality monitoring framework.

FIT-based population screening program that inadequate colonoscopy quality, lower ADR, is still the leading cause responsible for the risk of colonoscopy IC. FHbC, independently of the quality of colonoscopy, is also a significant predictor for IC in subjects who received complete colonoscopy after a positive FIT. Dedicated FHbCbased management of screenees may be helpful and can be applied to adjust screening logistics to decrease ICs and improve the effectiveness of CRC screening program.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

POST-COLONOSCOPY COLORECTAL CANCERS: PERSPECTIVES BASED ON JAPANESE INVESTIGATIONS Kinichi Hotta Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan Colonoscopy is only modality that allows visualization and removal of lesions throughout the entire colon in a single test. Previous colonoscopy and polypectomy are associated with 53-68% reduction in CRC mortality. However, a limitation of colonoscopy in the prevention of CRCs has been identified, particularly in the rightsided colon, and the problem of “Post-colonoscopy CRC (PCCRC)” has emerged. I will present PCCRC based on Japanese investigations in this session. Six patients (0.3%) were diagnosed PCCRC during 4-year follow-up in a randomized controlled study named Japanese polyp study.

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Moreover, 0.3% of PCCRC were diagnosed in an out patients clinic named TF clinic during 12-year data base including 6268 patients. In conclusion, flat-depressed lesions may represent the most likely frequent lesion for PCCRCs, given their morphological features which make them difficult to detect by colonoscopy. Detection of these lesions is likely to be influenced by factors such as blind spots during colonoscopy, poor bowel preparation and lesions which may be characterized as rapidly growing. To prevent PCCRC colonoscopy needs to be performed with these lesions in mind.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

CHARACTERISTICS AND SURVIVAL OF POST-COLONOSCOPY COLORECTAL CANCER IN KOREA Jae Myung Cha Division of Gastroenterology, Department of Internal Medicine, Kyung Hee University Hospital at Gang Dong, University of Kyung Hee School of Medicine, Seoul, Korea Post-colonoscopy CRC (PCCRC) is a CRC detected within recommended interval after a negative colonoscopy for colorectal cancer (CRC).

We can summary characteristics and survival of PCCRC in Korea from five Korean studies. In the first study,1 PCCRC was defined as an invasive CRC detected at colonoscopy1-5 years later following a normal colonoscopy between 20012004. The incidence of PCCRC was 1.5%. About 40% of them may be caused by missed lesion and 60% of them may be caused by new cancer.

In the second study,2 PCCRC was defined as a CRC detected after 1-5 years later following a negative index colonoscopy between 20132014. With this definition, PCCRC rate was 8.7%. In this study, proximal tumor location and MSI positivity were more frequently detected in PCCRC than sporadic cancers. However, there was no significant difference between two groups for tumor size, TNM stage, histological grade and mucinous cancers. In a third multicenter, retrospective study,3 PCCRC was defined as an invasive CRC detected within 5 years of index colonoscopy or 3 years after complete of highrisk adenoma. In this study, PCCRC rate was 0.2%. In this study, PCCRC were predominantly detected in the proximal location than distal colon, however, other clinico-pathological features as well as clinical outcomes were not significantly

different between the two groups. During 60 months follow-up period, survival was not significantly different between two groups. For the suspected causes of PCCRC, most common cause was missed lesion 54.7%, followed by incomplete resection 24.5% and newly developed cancer 20.8%. The fourth study focused on PCCRC after a positive fecal test.4 In this study, PCCRC was defined as a CRC detected within 6-60 months after negative index colonoscopy between 2005 and 2010. In this study, PCCRC rate was 10.3%. However, this study was unique as all colonoscopies were performed in subjects with a positive FIT result. A multivariate Cox proportional-hazard regression analysis showed that male and old age at index colonoscopy were significantly associated with the increased risk of PCCRC. Compared with screening-detected CRCs, PCCRC are likely to occur in community hospital than general hospital, in the proximal colon than distal colon, and at localized stage than regional stage or metastatic stages. In the final study using National Health Insurance Service database,5 PCCRC was defined as a CRC diagnosed within 12-120 months after index colonoscopy with a negative result. During the 5-year study period, annual PCCRC rate has increased by 2 fold, from 5.8% to 10.9%. In this study, the risk factors of PCCRC included older

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2019 TDDW age, male sex, higher socioeconomic status, nonsmoking, and proximal tumor location. The 5-year survival rate in patients with PCCRC was similar to those with detected CRC. In addition, the 5-year survival rate of PCCRC was worse than that of screening-detected CRC, but better than that of symptom-detected CRC. In summary, increasing PCCRC rate may reinforce the critical importance of improving the quality of colonoscopy in Korea. Old age, male sex, proximal location, higher socioeconomic status and smoking were predictive factors of PCCRC in Korea. Five-year survival rate of PCCRC was similar to that of colonoscopydetected cancers.

References: 1.

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Lee HH, Kim SK, Choi HH, et al. Postcolonoscopy colorectal cancers in averagerisk Korean subjects with a normal

initial colonoscopy. Turk J Gastroenterol 2016;27:17-22.

2.

L e e K W, P a r k S K , Ya n g H J , e t a l .

Microsatellite instability status of interval colorectal cancers in a Korean population.

Gut Liver 2016;10:781-785.

3.

Kim KO, Huh KC, Hong SP, et al. Frequency and characteristics of interval colorectal cancer in actual clinical practice: A KASID multicenter study. Gut Liver 2018;12:537-543.

4.

Lee CK, Choi KS, Eun CS, et al. Risk and characteristics of postcolonoscopy interval colorectal cancer after a positive fecal test: A nationwide population-based study in Korea.

Cancer Res Treat 2018;50:50-59.

5.

Cha JM, Kim HS, Kwak MS, et al. Features of postcolonoscopy colorectal cancer and survival times of patients in Korea. Clin Gastroenterol Hepatol 2019;17:786-788.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

CLINICAL OUTCOMES OF CRC DETECTED BY DIFFERENT DETECTION MODES WITHIN FIT SCREENING PROGRAM Wen-Feng Hsu Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Background: Survival of colorectal cancer (CRC) detected within a screening program may largely affect effectiveness of screening. Survival of CRC by different detection modes within fecal immunochemical test (FIT)–based screening program is, however, rarely reported.

Methods: CRCs with various detection modes within a population-based FIT screening program comprise the study cohort. Totally 8,992 CRCs were identified from the cohort who were considered as eligible for screening during 20042012 in Taiwanese CRC Screening Program and were followed up until 2016. Their survival status was compared stratifying with different detection modes: screening-detected CRC, FIT interval cancer (IC), colonoscopy IC, and clinically diagnosed CRC (colonoscopy noncompliers).

Multivariable analyses were conducted with Cox proportional hazards regression models.

Results: Colonoscopy IC, FIT IC, and CRC in colonoscopy noncompliers presented at a more

advanced (stage III/IV was 40.5%, 44.3%, and 42.7%, respectively) compared with screeningdetected CRCs (prevalent: 37.8%, subsequent: 35.3%). The 5-years survival rate was higher for subsequent screening-detected CRCs and worst in FIT IC and CRC in colonoscopy noncompliers.

In multivariable analysis, when compared with subsequent screening-detected CRCs, CRCs in colonoscopy noncompliers, the adjusted hazard ratio (aHR) and its 95% confidence interval (CI) for CRC death was 1.25 (1.04-1.50) for prevalent screening-detected CRCs, 1.62 (1.21–2.18) for colonoscopy ICs, 1.79 (1.48–2.15) for FIT ICs, and 1.95 (1.61-2.37) for CRC in colonoscopy noncompliers.

Conclusions: Interval CRC, including FIT IC and colonoscopy IC, and CRCs in colonoscopy noncompliers—had worse survival than screening-detected CRCs. Screening organizers should elaborate on relevant aspects of the screening program to improve screening effectiveness.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

PRESENT AND FUTURE OF COLONIC STENTING FOR COLORECTAL CANCER IN JAPAN Shuntaro Yoshida Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Colorectal cancer (CRC) is one of the most common malignancies and a major cause of cancer death with an estimated 1.2 million cases annually worldwide. Colonoscopy is considered the gold standard for CRC screening, however, it sometimes fails to detect CRC; such cases have been referred as post-colonoscopy CRC (PCCRC). The majority of PCCRC are advanced cancers, some of which are diagnosed with colorectal obstruction. Colonic stenting is considered as one of an effective treatment for intestinal decompression in obstructive CRC. However, many physicians remain hesitant to perform colonic stenting as bridge to surgery (BTS) in a curative setting, since it has been suggested to adversely affect oncological outcomes of CRC patients. We launched the Japan Colonic Stent Safety Procedure Research

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Group (JCSSPRG) with the purpose of ensuring the safe use of colonic stenting in Japan, as soon as this procedure was covered by health insurance in 2012. Recently, JCSSPRG has conducted a prospective randomized controlled trial to verify whether decompression by colonic stenting as BTS is non-inferior to surgery without stenting (considered as the standard treatment) for stage II and III left-sided obstructive CRC (UMIN-CTR000026158). The primary endpoint of this study, named COBRA trial, is disease-free survival of 3 years, which is an index of oncological outcome for CRC after curative resection. In this presentation, we will show data of our previous prospective studies which provided the basis for planning COBRA trial and discuss the future of colonic stenting for obstructive CRC.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW POST-COLONOSCOPY COLORECTAL CANCER: FROM PRACTICE TO SCREENING PROGRAM PERSPECTIVES

EFFECTIVE COLORECTAL CANCER SCREENING AND SURVEILLANCE IN A YOUNG POPULATION Nam Hee Kim Preventive Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea Screening colonoscopy and polypectomy are known to be the most effective strategies to reduce the incidence and mortality of colorectal cancer (CRC).1 Current guideline recommends that persons at average-risk of CRC commence screening colonoscopy at 50 years of age. 1 Accordingly, the incidence and mortality rate of CRC have decreased in persons aged ≥50 years during the last few decades.2 In contrast, the incidence of CRC in persons aged <50 years has recently increased.2 Moreover, younger patients with CRC have more aggressive disease and worse outcomes than older patients.3 Because young persons aged <50 years belong to the economically active population, an increase of CRC in this demographic will lead to future socioeconomic burdens. Therefore, young-onset colorectal neoplasia (CRN) including CRC and its precursor (colorectal adenoma) is a timely concern. However, limited medical resources have hindered the implementation of colonoscopy for CRC screening in persons aged <50 years. Fecal immunochemical test (FIT) is currently regarded as the best available noninvasive CRC screening tool and it can be an alternative screening method for persons aged <50 years.4 Colonoscopy for individuals who show a positive FIT result may be cost-effective compared with primary screening with colonoscopy in a young population. 5 FIT

typically provides a binary result (“negative” or “positive”) to identify individuals with values above a predetermined cut-off concentration to meet the requirements for colonoscopy, however, quantitative FIT allows for assessment of fecal hemoglobin (f-Hb) concentration. Several studies have shown that high f-Hb concentrations correlate with an increased risk of advanced CRN (ACRN) or CRC.6 In addition, many studies have reported that clinical factors such as age, male sex, smoking, and obesity increase the risk of ACRN or CRC.7-11 We hypothesized that combining FIT results (binary result or f-Hb concentration) and clinical risk factors may provide better diagnostic yield for detecting ACRN and CRC in a young population, and performed several studies to answer this question.6,7,11-15 Surveillance colonoscopy after polypectomy is another important issue to consider in a young population. Current guidelines recommend that intervals for surveillance colonoscopy should be based on the characteristics of adenoma detected at the time of index colonoscopy. 16 However, these guidelines have focused only on patients aged ≥50 years and no specific recommendations have been provided for the optimal timing/interval of postpolypectomy surveillane colonoscopy in patient aged <50 years because of the paucity of

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2019 TDDW reliable clinical data in this age group. Given that older age is a risk factor for the development of metachronous ACRN17, we hypothesized that the risk of metachronous CRN in patients aged <50 years may be lower than that in patients aged ≥50 years, and performed several studies to answer this question.18-20

6.

Today, I would like to introduce our findings on these issues, under the heading “Effective colorectal cancer screening and surveillance in a young population”.

Kim NH, Kwon MJ, Kim HY, Lee T, Jeong SH, Park DI et al. Fecal hemoglobin concentration is useful for risk stratification of advanced colorectal neoplasia. Dig Liver Dis. 2016; 48: 667-672.

7.

Park CH, Kim NH, Park JH, Park DI, Sohn CI, Jung YS. Individualized colorectal cancer screening based on the clinical risk factors: beyond family history of colorectal cancer.

Gastrointest Endosc. 2018; 88: 128-135.

8.

Jung YS, Ryu S, Chang Y, Yun KE, Park JH, Kim HJ et al. Risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years. Gastrointest Endosc. 2015; 81: 637-645.e637.

9.

Kim NH, Jung YS, Park JH, Park DI, Sohn CI. Influence of Obesity and Metabolic Abnormalities on the Risk of Developing Colorectal Neoplasia. Dig Dis Sci. 2018; 63: 3126-3133.

for Early Colonoscopy to Detect Advanced Colorectal Neoplasms. Gastroenterology.

2016; 150: 617-625.e613.

References: 1.

2.

3.

4.

5.

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Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017; 112: 1016-1030.

Wolf AMD, Fontham ETH, Church TR, Flowers CR, Guerra CE, LaMonte SJ et al.

Colorectal cancer screening for averagerisk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin.

2018; 68: 250-281.

Chiang JM, Chen MC, Changchien CR, Chen JS, Tang R, Wang JY et al. Favorable influence of age on tumor characteristics of sporadic colorectal adenocarcinoma: patients 30 years of age or younger may be a distinct patient group. Dis Colon Rectum. 2003; 46: 904-910.

Robertson DJ, Lee JK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA et al.

Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US MultiSociety Task Force on Colorectal Cancer.

Gastroenterology. 2017; 152: 1217-1237. e1213.

Chiu HM, Ching JY, Wu KC, Rerknimitr R, Li J, Wu DC et al. A Risk-Scoring System Combined With a Fecal Immunochemical Test Is Effective in Screening High-Risk Subjects

10. Kim NH, Jung YS, Yang HJ, Park SK, Park JH, Park DI et al. Association Between Cotinine-verified Smoking Status and Risk of Colorectal Neoplasia. J Clin Gastroenterol.

2019; 53: e107-e112.

11. Kim NH, Jung YS, Yang HJ, Park SK, Park JH, Park DI et al. Prevalence of and Risk Factors for Colorectal Neoplasia in Asymptomatic Young Adults (20-39 Years Old). Clin Gastroenterol Hepatol. 2019; 17: 115-122.

12. Kim NH, Park JH, Park DI, Sohn CI, Choi K, Jung YS. The fecal immunochemical test has high accuracy for detecting advanced colorectal neoplasia before age 50. Dig Liver Dis. 2017; 49: 557-561.

13. Park CH, Jung YS, Kim NH, Park JH, Park DI, Sohn CI. Usefulness of risk stratification models for colorectal cancer based on fecal hemoglobin concentration and clinical risk factors. Gastrointest Endosc. 2019; 89: 12041211.e1201.

2019 TDDW 14. Jung YS, Park CH, Kim NH, Park JH, Park DI, Sohn CI. A combination of clinical risk stratification and fecal immunochemical test is useful for identifying persons with high priority of early colonoscopy. Dig Liver Dis. 2018; 50: 254-259.

15. Jung YS, Park CH, Kim NH, Park JH, Park DI, Sohn CI. Colorectal cancer screening with the fecal immunochemical test in persons aged 30 to 49 years: focusing on the age for commencing screening. Gastrointest Endosc.

2017; 86: 892-899.

16. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology.

2012; 143: 844-857.

17. Park SK, Kim NH, Jung YS, Kim WH, Eun CS, Ko BM et al. Risk of developing advanced colorectal neoplasia after removing

high-risk adenoma detected at index colonoscopy in young patients: A KASID study. J Gastroenterol Hepatol. 2016; 31: 138-144.

18. Jung YS, Kim NH, Park JH, Park DI, Sohn CI. Appropriate Surveillance Interval after Colonoscopic Polypectomy in Patients Younger than 50 Years. J Korean Med Sci. 2019; 34: e101.

19. Kim NH, Jung YS, Park JH, Park DI, Sohn CI. Risk of developing metachronous advanced colorectal neoplasia after colonoscopic polypectomy in patients aged 30 to 39 and 40 to 49 years. Gastrointest Endosc. 2018; 88: 715-723.

20. Kim NH, Jung YS, Lee MY, Park JH, Park DI, Sohn CI. Risk of Developing Metachronous Advanced Colorectal Neoplasia After Polypectomy in Patients With Multiple Diminutive or Small Adenomas. Am J Gastroenterol. 2019.

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2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

SOFOSBUVIR-BASED DIRECT ACTING ANTIVIRALS: TO RENAL INJURY OR NOT? Chen-Hua Liu Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Chronic hepatitis C virus (HCV) infection is a major health problem that affects 71 million people worldwide. Patients with chronic HCV infection may present with various hepatic and extrahepatic manifestations which lead to substantial morbidity and mortality. In contrast, the long-term health outcome improves following successful HCV eradication by antiviral therapies.

Owing to the excellent efficacy and safety as well as the short treatment duration, the use of interferon (IFN)-free direct acting antivirals (DAAs) has become the standard-of-care for managing HCV. Sofosbuvir (SOF) is a pyrimidine nucleotide analogue which acts as the HCV ribonucleic acid (RNA) chain terminator by inhibiting HCV nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase following intrahepatic activation to uridine triphosphate form. Dephosphorylation results in the formation of inactive metabolite (GS331007) that undergoes extensive renal excretion.

Clinically, SOF is administered once-daily with pangenotypic potency, well tolerability and a high genetic barrier to drug resistance. Furthermore, SOF can be used in combination with NS3/4A protease inhibitors (PIs), NS5A inhibitors, and/or ribavirin (RBV) to achieve high rates of sustained virologic response (SVR). Therefore, applying SOF-based DAAs for HCV is welcome to most treating physicians.

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Following the widespread use of SOF-based DAAs for treating HCV in different populations, a large-scale real-world HCV-TARGET study enrolling 1,789 patients indicated that patients with a baseline eGFR ≤ 45 mL/min/1.73m2 were associated with a higher risk of worsening renal function than those with a baseline eGFR > 45 mL/min/1.73m 2 following SOF-based DAAs. Moreover, three retrospective studies showed that SOF-based DAAs negatively affected the ontreatment and off-therapy eGFR. On the contrary, other studies showed that the use of SOF-based DAAs did not worsen the eGFR. Because most studies were retrospective in nature without protocol-defined time point for eGFR assessment or patient election, and did not enroll patients receiving SOF-free DAAs as the controls, we conducted a prospective study to evaluate the evolution of eGFR in patients with chronic HCV infection receiving SOF-based or SOF-free DAAs. Between February 2015 to July 2018, 684 patients with chronic HCV infection receiving IFN-free DAAs for 12 weeks were prospectively assessed for eligibility in Taiwan.

After excluding patients with decompensated cirrhosis, CKD stage 4 or 5, post-transplantation, HBV or HIV coinfection, the remaining 481 patients receiving SOF-based (n = 308) and SOF-free (n = 173) were enrolled in the study.

2019 TDDW We further excluded patients who did reach the SVR24 time point. Finally, a total of 441 patients (SOF-based patients: 279; SOF-free patients: 162) were included in the final analysis. To reach a fair comparison, all patients received protocoldefined estimated glomerular filtration rate (eGFR) assessment by CKD-epidemiology collaboration (CKD-EPI) equation at baseline, on-treatment weeks 1, 2, 4, 6, 8 and 12, and off-therapy weeks 4, 8, 12 and 24 during the study period. Among the scheduled 4,851 test for eGFR, only 57 tested (1.2%) missed the assessment. We used a timedependent generalized linear mixed effect model (GLM), a powerful tool to assess the evolution of eGFR, to compared the changes of eGFR in patients receiving SOF-based or SOF-free DAAs. We also took into other potential factors that may affect the eGFR evolution, including age, sex, BMI, RBV use, concomitant nephrotoxic agent use, baseline CKD stage, DM, HTN in the uniand multi-variate analyses.

Univariate analyses showed that the use of SOF-based DAAs was associated with a significantly eGFR decline, compared to the use of SOF-free DAAs (p = 0.002) equation.

Multivariate analyses showed that age increase per 1-year (slope coefficient difference: -0.05 mL/ min/1.73m2; 95% CI: -0.05 to -0.04, p < 0.001), the use of SOF-based DAAs (slope coefficient difference: -0.34 mL/min/1.73m2; 95% CI: -0.51 to -0.24, p < 0.001), and more advanced CKD stage (slope coefficient difference: -1.45 mL/min/1.73m2; 95% CI: -1.60 to -1.20, p < 0.001, CKD stage 1 vs. stage 2; slope coefficient difference: -3.62 mL/ min/1.73m2; 95% CI: -3.93 to -3.31, p < 0.001, CKD stage 1 vs. stage 3) were independently associated with eGFR decline in patients receiving DAAs. We concluded that increasing age, SOF-based DAA usage, and baseline more advanced CKD stage were independent factors for eGFR decline during IFN-free DAAs for HCV patients.

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THE 3RD JOINT SESSION BETWEEN TDDW â&#x20AC;&#x201C; JDDW â&#x20AC;&#x201C; KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

OPTIMIZING DAA TREATMENT FOR CHRONIC HEPATITIS C LESSONS FROM JAPANESE EXPERIENCE Tatsuya Kanto The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Tokyo, Japan Japan has a national action plan for addressing viral hepatitis called, Basic Act on Hepatitis Measures, established in 2009.

Basic Guidelines for Promotion of Control Measures for Hepatitis is issued in 2011 and was updated in 2016, comprising 9 principles in order to promote measures to prevent hepatitis B and C (Oza N, Kanto T, Hepatol Res 2017). Realworld clinical data have proven that direct antiviral agents (DAAs) successfully eradicate HCV from more than 95% of the infected patients. In Japan, most of DAAs have been approved and registered, which enables us to choose multiple treatment options. In addition, for patients on treatment, drug prices of DAAs and examination expenses should be covered by special subsidy program for viral hepatitis. The national and local government cover the amount in excess of 100200 USD of the cost of treatment.

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In the clinical practice in Japan, optimization of DAAs treatment has been done based on HCV genotypes, stages of liver disease (chronic hepatitis or compensated/decompensated cirrhosis), prior experience of DAAs and the pattern of resistance-associated substitutions (RAS) on treatment. Of particular importance, meticulous care is needed for the treatment of patients with prior DAA failure and decompensated liver cirrhosis. Such tailored DAA treatment is guided by the Guidelines for the management of hepatitis C virus infection, updated and issued from Japan Society of Hepatology (JSH). Several advantages have been prevailed in Japanese health care systems for patients with viral liver disease compared to those in Asian countries.

Therefore, Japan should take a lead in promoting elimination of viral hepatitis from this region by sharing our experiences in the clinical settings.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

PAST AND CURRENT STATUS OF DAA THERAPY FOR CHC IN KOREA Jung Hyun Kwon Internal Medicine, The Catholic University of Korea, Seoul, Korea Division of Hepatology, Department of Internal Medicine, Incheon St. Mary’s Hospital, Incheon, Korea Hepatitis C virus in Korea Chronic hepatitis C (CHC) infection poses a global healthcare burden, being associated with serious complications if untreated. Asian patients including Korean achieve higher sustained virologic response (SVR) rates following interferon (IFN)-based therapy than non-Asians.1 Recently, oral direct acting antiviral agents (DAAs) against HCV infection have been developed. Oral DAA with a cure rate of over 90% became available in Korea since 2015. There have been two times revise of CHC guidelines in Korean Academy liver (KASL) in 2015 and 2017.2,3 However, a lack of governmental policy (screening, diagnosis, management of HCV) and the high prices of the drugs remain as a barrier to treatment of HCV infection.4 In 2015, there was a hot topic about that clustered outbreaks of HCV infection associated with reuse of disposable syringes were identified in several local clinics of Korea. Although current Korea national health insurance system covered most of indications of DAA, and patients pay 30% of drug price new DAAs, there is no screening program for HCV infection in national health check program unlike HBV. In cost-effect analysis, one-time HCV screening and treatment in Korean people

aged 40–70 is likely to be highly cost-effective compared to the current practice of no screening.5 The prevalence of anti-HCV-positive patients among Korean adults aged 20 years or older is 0.6 to 0.8%, and the prevalence rates in southern coastal area are high. 4,6-9 In previous reports, 65.1% of HCV infected patients was unaware of infection, and 72.2 % of anti-HCV Ab positive patients did not receive RNA test.4,7 In East Asian countries including Taiwan, genotype 1b is the most dominant subtype in Korea. Genotype 2 is also prevalent in Japan, Korea, and Southern Taiwan.4,7 Here, I will focus on the real world data of genotype 1 and 2 of CHC in Korea.

Past status of DAAs (year 2015~2017) Korean patients with CHC have been treated with DAA since 2015. Although Korea has a well‐ developed national health insurance system, the selection of DAAs was limited. There was a gap between guidelines and insurance coverage. It was recommended that all patients with CHC 1b were checked for resistance‐associated variants (RAV) against nonstructural protein (NS) 5A inhibitors and then were treated with daclatasvir and asunaprevir (DCV + ASV). If patients were not suitable for DCV + ASV treatment because of decompensated liver cirrhosis or RAV positivity for

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2019 TDDW NS5A or genotype 1a, daclatasvir, and sofosbuvir (DCV + SOF±RIB) or sofosbuvir/ledipasvir (SOF/ LDV±RIB) regimens could be chosen.2 For CHC 2, SOF + ribavirin (SOF + RIB) is only available regimen.2 In one report about RAV test for 512 Korean CHC 1b patients, variations at position L31M and/ or Y93H were detected in 58 (10%) patients. Two patients had variations at both L31M and Y93H. “Indeterminate” results for RAV testing were reported in 21 (3.7%) patients.10 The SVR12 was 94.0% in the DCV+ASV, and a total of 93.3% of SVR12 even in the RAV‐“indeterminate” patients was not difference 95.0% in the RAV‐negative patients.10 However, SVR12 was 28.6% in RAV positive patients. In other report (526 patients), negative RAS was associated with higher SVR (96.3%) than with “undetermined RAS” (85.7%) or “not tested for RAS” (84.4%).11 In CHC 1 patients who were not suitable for DCV+ASV regimens by an initial strategy (called as “difficult to treat” group), SOF based regimens achieved 98~100% of SVR12 (40/41, 54/55, 11/11) in several Korea real world datas.10 In CHC 2 patients, 96~100% of SVR12 were achieved in over 1,200 patients (including academic conference reports).12,13 However, age ≥70 years, with liver cirrhosis, and female gender were associated with ribavirin dosage reduction.

Thus, SVR can be achieved with <1,000 mg of ribavirin, with an optimal dosage of 15 mg/kg.12 So, there is a need of ribavirin- free regimens in certain population.

Current status of DAAs (year 2017~ 2019) The gap between guidelines and insurance coverage has been narrower since introduction of several drugs (EBR/GZR, OBV/PTV/r+DSV in year 2017 and G/P in year 2018).3 The most recent pan-genotypic regimen (G/P) is possible to simplify the treatment and RIB free regimens.

SOF/LDV regimen is also permitted in CHC 2 patients in year 2019 as well as CHC 1 patients.

In addition, insurance coverage has been changed from limited option for each genotype to several regimens. Sofosbuvir/velpatasvir (SOF/

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VEL), sofosbuvir/velpatasvir/voxilaprevir (SOF/ VEL/VOX) are not available yet. Simeprevir (SIM) is not available in Korea.14 In real world data for EBR/GZR in Korean CHC 1b patients, SVR12 was achieved by 73 of 74 (98.6%) patients.15 A total of 16 patients had NS5A RAV positivity at baseline (16/73, 22%), all of whom achieved SVR12 unlike DSV + ASV regimens.10, 15 In another 845 cohort study, 98 % (50/51), 100% (32/32), and 98% (58/59) of SVR12 for CHC 1 patients were achieved in EBR/GZR, OBV/PTV/r+DSV, LDV/SOF±RBV regimens, respectively. Finally, G/P regimens in Korean 265 CHC patients showed 99.2% (132/133, 1 missing data) in genotype 1 and 98.5% (130/132, 1 virologic fail, 1 d/c) in genotype 2 in pooled analysis from 5 phase II and III trials from Korea.

Conclusions From the real-world data, optimizing the choice of DAAs according to the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or RAV test resulted in high SVR among CHC Korean patients. Drug availability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries. There is a need to improve current clinical practices for HCV management in Asia, including effective screening, disease awareness, and prevention programs, and to further understand the cost-effectiveness of IFNfree regimens.16

References: 1.

Kwon JH, Bae SH, Lee YJ, et al. The virological response in Koreans infected with HCV genotype 1 did not differ between groups treated with a full dose or reduced dose (>/=80 % full dose) of peginterferon alfa-2a: a prospective randomized multicenter trial. Hepatol Int 2013;7:1000-9.

2.

KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol

2019 TDDW 2016;22:76-139.

3.

2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C. Clin Mol Hepatol 2018;24:169-229.

4.

Jeong SH, Jang ES, Choi HY, et al. Current status of hepatitis C virus infection and countermeasures in South Korea. Epidemiol Health 2017;39:e2017017.

5.

Kim DY, Han KH, Jun B, et al. Estimating the Cost-Effectiveness of One-Time Screening and Treatment for Hepatitis C in Korea. PLoS One 2017;12:e0167770.

6.

Kim BK, Jang ES, Kim JH, et al. Current status of and strategies for hepatitis C control in South Korea. Clin Mol Hepatol 2017;23:212-218.

7.

K i m D Y, K i m I H , J e o n g S H , e t a l . A nationwide seroepidemiology of hepatitis C virus infection in South Korea. Liver Int 2013;33:586-94.

8.

Seong MH, Kil H, Kim YS, et al. Clinical and epidemiological features of hepatitis C virus infection in South Korea: a prospective, multicenter cohort study. J Med Virol 2013;85:1724-33.

9.

Shon HS, Choi HY, Kim JR, et al. Comparison and analysis of the prevalence of hepatitis C virus infection by region in the Republic of Korea during 2005-2012. Clin Mol Hepatol 2015;21:249-56.

10. Kwon JH, Yoo SH, Nam SW, et al. Clinical outcomes after the introduction of direct antiviral agents for patients infected with

genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea. J Med Virol 2019;91:1104-1111.

11. Jang ES, Kim KA, Kim YS, et al. Real-life effectiveness and safety of the daclatasvir/ asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: an emphasis on the pretreatment NS5A resistance-associated substitution test. J Med Virol 2019.

12. Yoon JH, Jun CH, Seo JH, et al. Sofosbuvir plus ribavirin for the treatment of hepatitis C virus genotype 2 in Korea: Whatâ&#x20AC;&#x2122;s the optimal dosage of ribavirin in real-world setting? J Dig Dis 2019;20:31-37.

13. Ahn SH, Lim YS, Lee KS, et al. A phase 3b study of sofosbuvir plus ribavirin in treatmentnaive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus. J Viral Hepat 2016;23:35865.

14. Yeon JE. Recent update of the 2017 Korean Association for the Study of the Liver (KASL) treatment guidelines of chronic hepatitis C: Comparison of guidelines from other continents, 2017 AASLD/IDSA and 2016 EASL. Clin Mol Hepatol 2018;24:278-293.

15. Lee YJ, Heo J, Kim DY, et al. An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection. Clin Mol Hepatol 2019.

16. Kao JH, Ahn SH, Chien RN, et al. Urgency to treat patients with chronic hepatitis C in Asia.

J Gastroenterol Hepatol 2017;32:966-974.

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THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

NEW BIOMARKERS IN PREDICTING HCC DEVELOPMENT IN CHB PATIENTS Tai-Chung Tseng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Chronic hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. A recent worldwide estimate suggests that 248 million individuals were hepatitis B surface antigen (HBsAg) positive. These individuals are at an increased risk of developing liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma; 15% to 40% of these individuals will develop these serious sequelae during their lifetime.

Nucleos(t)ide analogue (NA), which is reverse polymerase inhibitors, is the most common antiHBV therapy. It is effective in suppressing viral replication, but not achieving HBV cure, which is defined as HBsAg clearance. Therefore, it usually needs a prolonged NA therapy to achieve HBV control and understanding the risk factors of disease progression is mandatory.

For viral factors, hepatitis B viral load is a strong predictor for liver disease progression.

Serum HBsAg level serves as a complementary

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marker to viral load for the prediction of HBVrelated adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) is a novel marker and its level has been reported to be associated with HCC development. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression.

In terms of host factors, liver fibrosis severity and serum ALT level, a liver inflammation marker, are 2 important predictors for disease progression.

Other host genetic factors have been shown to be associated with disease progression but need more validations.

In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression, which may provide more information for timely antiviral therapy.

2019 TDDW

THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

TREATMENT OF HEPATITIS C IN SPECIAL POPULATIONS Goki Suda Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and reinfected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly.

Thus, there is an acute need for prompt treatment of HCV infection in these special populations.

However, previous standard anti-HCV treatment involved the use of interferon-based therapy.

In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events.

With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events. In this presentation, we present recent advances in antiHCV treatment for these special populations, especially focusing on hemodialysis patients.

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THE 3RD JOINT SESSION BETWEEN TDDW – JDDW – KDDW OPTIMIZATION OF DIRECT ANTI-VIRAL AGENT TREATMENT FOR HCV: CURRENT STATUS IN THE ASIA-PACIFIC REGION

HOW TO ENHANCE THE EFFICACY OF SYSTEMIC THERAPIES FOR HCC Su Jong Yu Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea Hepatocellular carcinoma (HCC) is an aggressive tumor that usually occurs late in the course of chronic liver disease and cirrhosis.

Despite the fact that surveillance program lead to early diagnosis in 40–50% of patients, at a point when potentially curative treatments are applicable, almost half of all patients with HCC ultimately receive systemic therapies including targeted and immune-based therapies based on positive results from phase 3 trials. However, the median overall survival remains about 1 year; thus, therapeutic breakthroughs are still needed.

The limited efficacy of systemic therapies against HCC can be linked to the existence of primary and the emergence of acquired drug resistance mechanisms. The identification of HCC subsets with distinct driver mutations or dysregulated pathways could lead to the development of individualized therapy options with increased treatment sensitivity. Scientists have been studying the molecular mechanism of HCC for years and large amounts of data on genetic and epigenetic abnormalities, gene expression profiles, microRNA expression profiles, metagenomics, proteomics, and metabolomics have been accumulating, and bioinformatics like systems biology is suggesting new perspectives in precision medicine. Recently, we obtained

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serum samples from HCC patients before sorafenib treatment and analyzed them using multiple reaction monitoring-mass spectrometry (MRM-MS), a high-throughput proteomics technic, and found targeted proteomic biomarkers for individualized sorafenib therapy. In the last years, many studies have clearly evidenced the complex molecular heterogeneity of HCC. Investigators tried to characterize the mutational landscape of liver cancer by whole exome sequencing to identify common aberrations patterns for the creation of distinct HCC subpopulations; however, the most common mutations are not actionable, and only ~25% of tumors harbor potentially targetable drivers. Therefore, the definition of robust biomarkers that could inform treatment decisions is a key challenge that needs to be addressed. In fact, based on recent data mostly obtained from the failed clinical trials, there are some ongoing biomarker driven clinical trials in HCC. These studies will provide information on the benefit of new drugs in selected cohorts of patients. Research on biomarkers of a response or primary resistance to immunotherapies is also advancing. Thus, the identification of key molecules/receptors/signaling pathways, classification of HCCs into subgroups according to their genomic and proteomic profiling and the assessment of their relevance as potential targets

2019 TDDW will be the main future challenge potentially influencing response to systemic therapies.

A growing number of studies that reported acquired resistance to systemic therapies also highlight uncovering the molecular and/ or immunological mechanisms responsible for the resistance is necessary for improving the survival rates of patients with HCC. Recently, our group utilized a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. We found that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor can synergistically increase the efficacy of sorafenib. Although some success has been seen with immune checkpoint inhibitors (ICIs) and cell-based immunotherapies like cytokineinduced killer (CIK) cells in HCC, a majority of HCC patients do not respond to therapy. HCC has been shown to induce several immune suppressor mechanisms in patients. These suppressor mechanisms range from myeloidderived suppressor cells (MDSCs), regulatory T cells (Tregs), functionally impaired dendritic cells, neutrophils, and monocytes to tumor associated macrophages (TAM). The accumulation of immunosuppressive cells may lead to an immunosuppressive tumor microenvironment (TME) as well as the dense fibrotic stroma which may contribute to immune tolerance. The combination of therapeutic regimens that both amplify tumor-specific immunity and counteract these immunosuppressive mechanisms are expected to strongly improve clinical outcomes of cell-based immunotherapy for HCC patients.

In addition, we can postulate that it is more beneficial for immune checkpoint inhibitors (ICIs) to combine potent effector cells like CIK cells because ICIs require eventually effector cells to

kill tumor cells. Currently, combinations of kinase inhibitors and immunotherapies are emerging as tools to boost responses of the immune system against HCC-derived neoantigens. These unprecedented outcomes (objective responses >45%) resulted in breakthrough therapy designation for bevacizumab and atezolizumab by the FDA. Two or 3 effective systemic therapies including ICIs and/or molecular targeted therapies and the addition of innovative combination therapies targeting immune suppressor cells like a phosphodiesterase-5 (PDE5) inhibitor may lead to increased immune recognition with a greater tumor response.

Though markedly different pathological processes are involved in chronic hepatitis B/ C and the development of HCC, there are some similarities between the two when considering the role of the immune system, with T cell exhaustion implicated in both. CD8+ T cells are integral in targeting and destroying both tumor cells and cells infected with hepatitis B virus (HBV)/ hepatitis C virus (HCV). Reversing immune dysfunction after directly-acting antiviral agents (DAAs) have been demonstrated. Permanent suppression of HBV and eradication of HCV have been achieved reduction of the global burden of HCC by improving liver immunity. From this, we might extrapolate that this in turn may impact on the immune surveillance in this population, thus may affect HCC treatment outcomes. Currently the clinical impact of the immune environment and altered immune surveillance is not clear, but insight into these processes in the post-DAA liver is improving, which may be crucial in how we shape our treatment.

In conclusion, omics and immunology research have improved the understanding of the biology of HCC, but this knowledge has not yet been translated into clinical practice.

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Young Investigator Award (YIA) ①

ALBUMIN-BILIRUBIN (ALBI) GRADE-BASED NOMOGRAM FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA UNDERGOING TRANSARTERIAL CHEMOEMBOLIZATION Shu-Yein Ho1,4, Yi-Hsiang Huang1,4,5, Chien-Wei Su1,4, Rheun-Chuan Lee2,4, Ming-Chih Hou1,4, Teh-Ia Huo1,3,6 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Radiology,Taipei Veterans General Hospital, Taipei, Taiwan2 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan3 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan4 Institute of Clinical Medicine, National YangMing University School of Medicine, Taipei, Taiwan5 Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan6

利用基於 Albumin-Bilirubin Grade 的 列線圖用於預測肝癌病患接受肝脈栓 塞化學療法的預後 何樹仁1,4 黃怡翔1,4,5 蘇建維1,4 李潤川2,4 侯明志1,4 霍德義1,3,6 臺北榮民總醫院內科部1 臺北榮民總醫院放射線部2 臺北榮民總醫院醫學研究部3 國立陽明大學醫學系4 國立陽明大學臨床醫學研究所5 國立陽明大學藥理學研究所6 Background: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is highly heterogeneous because of variable characteristics of tumor burden and liver dysfunction.

Aims: We aimed to propose and validate an albumin-bilirubin (ALBI) grade-based prognostic nomogram for HCC patients undergoing TACE. Methods: A total of 1051 patients with HCC undergoing TACE were randomly assigned to derivation (n=525) and validation (n=526) set in this retrospective study based on prospective

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data. The multivariate Cox proportional hazards model in derivation set was used to generate the nomogram. The predictive accuracy of the nomogram was evaluated by discrimination and calibration tests.

Results: In multivariate analysis, presence of ascites, ALBI grade 2-3, serum α-fetoprotein level ≥ 400 ng/mL, total tumor volume ≥ 396 cm 3 , presence of vascular invasion, and poor performance status were independently associated with decreased survival of patients in the derivation set. Each patient had an individualized score from 0-41 by adding up the points from these six prognostic predictors. The nomogram generated from the derivation set had a concordance index of 0.72 (95% confidence interval [CI]: 0.63-0.82). Discrimination test in the validation set provided a good concordance index 0.72 (95% CI 0.62-0.81) and the calibration plots consistently matched the ideal 45-degree reference line for 3- and 5-year survival prediction.

Conclusions: The ALBI grade-based prognostic model can well discriminate the survival in HCC patients undergoing TACE. The proposed easyto-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient in the precision medicine era.

2019 TDDW

②

REAL-WORLD EFFECTIVENESS AND SAFETY OF SOFOSBUVIR/ LEDIPASVIR VERSUS GLECAPREVIR/PIBRENTASVIR FOR PATIENTS WITH GENOTYPE 2 CHRONIC HEPATITIS C IN TAIWAN Sheng Feng Lin1, Kuo-Liang Wei1, Shui-Yi Tung1, Te-Sheng Chang1, Sheng-Nan Lu1,2, Chao-Hung Hung1,2 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

6 (2.7%) of SOF/LDV and 6 (2.4%) of GLE/PIB patients, respectively because of anorexia (n=1, SOF/LDV), sudden death (n=1, SOF/LDV), sepsis (n=1, SOF/LDV), hepatic decompensation (n=1, GLE/PIB), severe pruritus, (n=2, GLE/PIB), and other adverse reactions. Patients treated with GLE/ PIB had significantly higher total bilirubin levels at week 2 (p=0.002) and at week 4 (p=0.001) than those treated with SOF/LDV. Conclusions: In this real-world cohort study, treatment with SOF/LDV and GLE/PIB achieve similar treatment response with a low discontinue rate among patients with HCV genotype 2 infection. However, these two regimens result in different side effects that have to be cautiously monitored.

台灣基因型 2 型慢性 C 型肝炎患者使用 Sofosbuvir/Ledipasvir 與 glecaprevir/ Pibrentasvir 的真實世界有效性和安全 性之比較 林聖峰1 魏國良1 董水義1 張德生1 盧勝男1,2 洪肇宏1,2 嘉義長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院胃腸肝膽科系2 Background: The real-world data for the effectiveness and safety of sofosbuvir/ledipasvir (SOF/LDV) and glecaprevir/pibrentasvir (GLE/ PIB) in patients with chronic hepatitis C virus (HCV) genotype 2 infection remained limited.

Aims: The aim of this study was to compare their performance in a real-world setting in Taiwan.

Methods: A total of 471 compensated HCV genotype 2 patients who were treated with SOF/LDV for 12 weeks (n=222) or GLE/PIB for 8 weeks (n=198) or 12 weeks (n=51) were retrospectively enrolled. The safety and efficacy assessed by the sustained virological response 12 weeks off therapy (SVR12) were evaluated.

Results: By 23 June 2019, the rate of undetectable HCV RNA at end-of-treatment and SVR12 was 99.1% (213/215), and 92.3% (12/13), respectively, in patients receiving SOF/LDV compared to 100% (240/240), and 98.6% (139/141), respectively, in those with GLE/PIB based on the per-protocol analysis. Treatments were early discontinued in

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③

HIGH-DOSE PROTON PUMP INHIBITOR AND CULTUREGUIDED THERAPY IN THE THIRDLINE TREATMENT OF H. PYLORI INFECTION Kuang-Tsu Yang1, Deng-Chyang Wu2, Feng-Woei Tsay1, Wen-Chi Chen1, Chao-Hung Kuo2,3, Ping-I Hsu1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National YangMing University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan2 Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan3

幽門螺旋桿菌感染的第三線治療：高劑 量氫離子幫浦阻斷劑及細菌培養導向 治療 楊光祖1 吳登強2 蔡峯偉1 陳文誌1 郭昭宏2,3 許秉毅1 高雄榮民總醫院胃腸肝膽科暨陽明大學醫學系1 高雄醫學大學附設醫院腸胃內科2 高雄市立小港醫院3 Background: The Maastricht V/Florence Consensus Report recommends culture-guided therapy in the third-line treatment of H. pylori infection. Recent studies indicate that high-dose proton pump inhibitor (PPI) can improve cure rate of anti-H. pylori regimen.

Aims: To assess the efficacy of high-dose PPI and culture-guided therapy in the third-line treatment of H. pylori infection.

Methods: Consecutive H. pylori-infected patients with at least two previous failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose PPI and/or bismuth. They are categorized into three groups: (1) patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy (rabeprazole 20 mg QID and three effective antibiotics), (2) patients who had positive

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result of culture with one or two susceptible antibiotics were treated by culture-guided bismuthcontaining therapy (rabeprazole and tripotassium dicitrato bismuthate plus effective antibiotics), and (3) patients who had negative results of culture or whose culture data were unavailable were treated by empirical regimen (rabeprazole plus amoxicillin, tetracycline and levofloxacin) for 14 days. Post-treatment assessment by urea breath test was conducted at the end of week 8.

Results: A total of 123 patients participated in the study. The culture-guided therapy group (n=95; including non-bismuth quadruple therapy [n=49] and bismuth-containing therapy [n=46]) achieved a higher eradication rate (83.2% vs 64.3% P=0.032) than the empirical group (n=28).

Additionally, the former had fewer adverse events (71.6% vs 50%, P=0.033) and higher drug adherence (96.8% vs 82.1%; P=0.015) than the latter. Among the culture-guided group, patients receiving culture-guided non-bismuth quadruple therapy and those receiving bismuth-containing therapy had comparable eradication rate (85.7% vs 80.4%, P=0.492), adverse events (36.7% vs 19.6%, P=0.064) and drug adherence (98.0% vs 95.7%, P=0.609).

Conclusions: In the 3rd-line treatment of H. pylori infection, high-dose PPI and culture-guided therapy can achieve a higher eradication rate than high-dose PPI empirical therapy.

2019 TDDW

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PREVALENCE OF EXTRAINTESTINAL MANIFESTATIONS IN TAIWAN MODERATE TO SEVERE INFLAMMATORY BOWEL DISEASE PATIENTS TREATED WITH BIOLOGICS Tzung-Jiun Tsai1, Shu-Chen Wei2, Deng-Chyang Wu3, Jau-Min Wong2, Ping-I Hsu1, Taiwan IBD Research Consortium Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan3

and 105 with UC) were registered. Among them, 25 (9.7%) exhibited at least one EIM. Patients with CD and UC had no differences in the prevalence of EIMs (7.1% vs 13.3%; P=0.098). In patients with CD, the prevalence of articular, ophthalmic, cutaneous and hepatobiliary manifestations were 4.5%, 1.3%, 2.6% and 0%, respectively. In patients with UC, the prevalence of corresponding manifestations were 9.5%, 2.9%, 3.8% and 1%, respectively. Among all the IBD patients, the presence of EIM was not associated with any clinical characteristics including age, gender, alcohol drinking, smoking, type of IBD, history of appendectomy and history of bowel resection.

Conclusions: About 9.7% of moderate to severe IBD patients in Taiwan had at least one EIM.

台灣中重度發炎性腸道疾病接受生物 製劑治療之患者有腸道外症狀的盛行 率研究

蔡騌圳1 魏淑鉁2 吳登強3 翁昭旼2 許秉毅1 台灣IBD 研究團隊

高雄榮民總醫院胃腸肝膽科1 國立臺灣大學醫學院附設醫院內科部2 高雄醫學大學附設中和紀念醫院胃腸肝膽科3 Background: The prevalence of extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) patients in western countries ranges between 16% and 40%. Data on prevalence and risk factors of EIMs in inflammatory bowel disease patients in Taiwan are limited.

Aims: (1) To investigate the prevalence of EIMs in Taiwan moderate to severe IBD patients treated with biologics, and (2) to identify risk factors for EIM development in IBD patients.

Methods: The study population consisted of moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC) patients, who were treated by biologics in 14 tertiary Taiwan hospitals.

Demographic and extra-intestinal disorders of patients were analyzed. The diagnosis of EIMs was based on standard criteria and on specialist consultation.

Results: In total, 259 IBD patients (154 with CD

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AUTOPHAGY LC3 AND AXL EXPRESSION IN TUMORS SIGNIFICANTLY PREDICTS CLINICAL OUTCOME OF HEPATOCELLULAR CARCINOMA AFTER HEPATECTOMY

Tsung-Chin Wu3, Gin-Ho Lo3,5, Yaw-Sen Chen1,5, Pei-Min Hsieh5, Ming-Lung Yu6, Chih-Wen Lin1,2,3,4 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan1 Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan2 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan3 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan4 Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan5 Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan6 Background: Hepatocellular carcinoma (HCC) is the third common cause of cancer-related death in the world. Although the 5-year survival rate of individuals diagnosed in the early stage exceeded 50% after curative resection, these patients still had a high recurrence rate of approximately 60% after curative resection.

Hence, identifying biomarkers for HCC recurrence and overall survival (OS) could help to promote the clinical prognosis in HCC patients undergoing hepatectomy. Axl, a member of the Tyro3, Mer, and Axl family of tyrosine kinase receptors, regulates some aspects of cancer biology. Recently, Reichl et al. reported that high serum soluble Axl levels are correlated with vascular involvement and lymph node metastasis, and serum soluble Axl is a potential marker in the early diagnosis of HCC and the early prediction of HCC recurrence.

Moreover, several studies showed that Axl may be a negative predictor for HCC patients, and high Axl expression was positively associated with differentiation, lymph node metastasis, higher recurrence, and lower survival in HCC patients.

Furthermore, Axl expression is associated with increased tumor invasion and predicts a worse prognosis for HCC patients undergoing

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resection. Our previous studies showed that high LC3 expression in the liver and tumor microenvironments is strongly correlated with higher OS and lower HCC recurrence. However, the role of OS and HCC recurrence between Axl and the autophagy-related marker LC3 has never been discussed in the literature.

Aims: We will investigate the impact of Axl and LC3 expression on tumor recurrence and OS in HCC patients who underwent curative resection in the large-scale cohort.

Methods: We retrospectively included 535 HCC patients undergoing hepatectomy from 2010 to 2014. Axl and the autophagy-related marker LC3 were immunohistochemically assessed in tumors.

Results: Axl expression was significantly associated with advanced clinicopathological features, including cirrhosis, microvascular invasion, macrovascular invasion, tumor size, BCLC stage, recurrence, and mortality. HCC recurrence occurred in 245 patients, and 219 patients had mortality. The 5-year cumulative incidence of HCC recurrence and OS after HCC resection were 53.3% and 58.8%, respectively.

In Cox proportional analyses, patients with high Axl expression and high LC3 expression were significantly associated with HCC recurrence (hazard ratio [HR]: 3.85; 95% confidence interval [CI]: 2.95-5.02; p<0.001, and HR: 0.38; 95% CI: 0.26-0.55; p<0.001, respectively). In addition, HCC recurrence (HR: 2.87; 95% CI: 2.014.01, p<0.0001), microvascular invasion (HR: 1.85; 95% CI: 1.08-3.19, p=0.026), hepatitis B virus-related HCC (HR: 1.77; 95% CI: 1.

21-2.56, p=0.003), high Axl expression (HR: 1.66; 95% CI: 1.41-1.97, p<0.0001), antiviral therapy (HR: 0.54; CI: 0.38-0.76, p<0.001) and LC3 expression (HR: 0.41; 95% CI: 0.28-0.58, p<0.001) were significantly associated with mortality. Next, patients with a combination of high Axl and low LC3 expression had the highest risk of HCC recurrence (HR: 6.53; 95% CI: 4.1110.4, p<0.001) and mortality (HR: 6.66; 95% CI: 4.07-10.9, p<0.001). In patients with high Axl, low LC3, and combined high Axl and low LC3 expression, the 5-year cumulative incidence of HCC recurrence and OS was 77.9%, 73.3%, and 90.0% and 28.8%, 26.7%, and 16.8%, respectively.

Conclusions: High Axl expression in tumors is associated with aggressive tumor behavior and worse clinical outcomes. Furthermore, the combination of high Axl and low LC3 expression significantly predicts poorer prognosis in HCC patients who underwent hepatectomy.

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RELATIONSHIP BETWEEN POSTCOLONOSCOPY COLORECTAL CANCER AND QUALITY INDICATOR OF COLONOSCOPY Haruki Kaizuka1,Hayato Yamaguchi1,2,3, Yasuyuki Kawaga1, Kumiko Uchida1, Akihiko Sugimoto1, Masakatsu Fukuzawa1, Takashi Kawai3, Takao Itoi1 Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan1 Department of Gastroenterology and Hepatology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan2 Endoscopy Center, Tokyo Medical University Hospital, Tokyo, Japan3

TCS was 30.2%–52.8% (38.6%±6.6%). ADR of colonoscopists at the time of PCCRC detection (36.7%±5.9%) was significantly higher than that of colonoscopists who performed the last examination (34.9%±4.4%; p=0.034). The withdrawal time for negative colonoscopy (WTNC) was significantly longer for PCCRC detection (494.3±253.8 s ) than at the last examination (579.5±243.6 s; p=0.010).

Conclusions: Most PCCRC cases showed lesions that were missed during the previous colonoscopy. We suggest that caution should be practiced to avoid missing flat NPG-type tumors.

Background: Post-colonoscopy colorectal cancers (PCCRC) pose a major challenge that affects colonoscopy surveillance intervals and CRC-associated mortality.

Aims: To elucidate the association between clinical characteristics of PCCRC and quality indicators (QIs) of colonoscopy.

Methods: Patients with PCCRC who underwent total colonoscopy (TCS) and who were histologically diagnosed with adenocarcinoma within 6 months to 5 years of the last examination were included in this study. PCCRC and normally detected cancer (NDC) identified within the same period were compared in terms of their clinicopathological characteristics. Furthermore, PCCRC with invasion depth T1a or shallower were classified into group A and those of T1b or deeper were classified into group B. QI at PCCRC detection were compared to those at the last examination.

Results: There were 76 cases of PCCRC among the 1513 cases of CRC. Patients with PCCRC had a significantly higher rate of colon surgery history than those with NDC (PCCRC: 25/76; NDC: 31/1437; p < 0.001), but the invasion depth in these patients was significantly shallower (PCCRC: ≤T1a/≥T1b, 42/34; NDC: ≤T1a/≥T1b, 470/967; p < 0.001). Among patients with PCCRC, 42 were in group A and 34 were in group B, and group B had significantly more number of NPG-type CRC than those of PG-type CRC (p=0.018). ADR of colonoscopists performing

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USEFULNESS OF EUS-GUIDED ANTEGRADE STENTING WITH HEAPTICOGASTROSTOMY FOR MALIGNANT BILIARY OBSTRUCTION Makoto Arashiyama, Kenjiro Yamamoto, Atsushi Sofuni, Takayoshi Tsuchiya, Kentaro Ishii, Reina Tanaka, Ryosuke Tonozuka, Mitsuyoshi Honjo, Shuntaro Mukai, Mitsuru Fujita, Kazumasa Nagai, Yasutsugu Asai, Yukitoshi Matsunami, Takashi Kurosawa, Hiroyuki Kojima, Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan Background: Recently novel endoscopic ultrasound-guided biliary drainage (EUSBD) technique compounded of EUS-guided hepaticogastrostomy (EUS-HGS) and EUSguided antegrade stenting (EUS-AS) (EUSAS+HGS) has been reported to decrease adverse events, keep longer stent patency, and easily perform re-intervention for malignant biliary obstruction (MBO). However, only a few small reports have evaluated this technique. In addition, conventional biliary metallic stent was used for EUS-HGS stenting.

Aims: This present study was to evaluate the utility of EUS-AS+HGS for MBO using the dedicated HGS plastic stent.

Methods: 33 consecutive patients (male 21, female 12) who underwent EUS-AS+HGS for MBO from October 2014 to June 2018 at Tokyo Medical University Hospital were retrospectively reviewed.

Results: EUS-AS+HGS was carried out simultaneously in 23 patients and sequentially in 10 patients. The disease causing to MBO were as follows; pancreatic cancer in 17 patients, gastric cancer in 4, bile duct cancer in 3, ampullary cancer in 2, duodenal cancer in 1, and metastasis from other cancer in 6. Technical and clinical success rates were both 100% (33/33). Adverse events were seen in 9.1% (3/33); 2 mild biliary peritonitis which were all successfully managed conservatively, and 1 puncture bleeding were treated by interventional radiology. Median

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duration of stent patency after EUS-AS+HGS including stent dysfunction, patient death, surgery, and last follow-up was 71 days (95% CI 37 to 506 days). Especially stent dysfunction was seen in 5 (15.2%) patients in 267, 263, 216, 135, and 65.

Conclusions: Novel EUS-BD technique, EUSAS+HGS was feasible procedure for MBO that longer duration of stent patency can be expected.

Furthermore, using the dedicated PS for EUSHGS seems to be safer method.

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ENDOSCOPIC TREATMENT STRATEGY FOR WALLED OFF NECROSIS AFTER SEVERE ACUTE PANCREATITIS IN ACCORDANCE WITH THE MORPHOLOGICAL FEATURE Takaaki Iijima, Shuntaro Mukai, Atsushi sohuni, Takayoshi Tsuchiya, Ryosuke Tonozuka, Mitsuyoshi Honjo, Takao Itoi

events rate was 8%, 5.9%, 18%, 24%, 22% and a mortality rate was 0%, 5.9%, 0%, 5.9%, 22%,, respectively.

Conclusions: The treatment results for type II-IV WON with only EUS-TD + DEN were poorer than type I WON. For the treatment strategy of type IIIV WON, additional endoscopic drainage or hybrid approach should be added actively in accordance with the morphological feature.

Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan Background: Recently, the efficacy of EUSguided transluminal drainage (EUS-TD) and direct endoscopic necrosectomy (DEN) for walled-off necrosis (WON) has been reported, but refractory cases remain.

Aims: We previously reported the relation between the refractory cases and their complicated morphological features. Herein, we classified WON treated at our institution according to their morphological features and evaluated the treatment strategy.

Methods: One hundred cases of WON treated between October 2010 and September 2018 were evaluated retrospectively. WON was diagnosed following the revised Atlanta Classification.

Results: WON was classified as follows, type Ia (unilocular, size<10cm, 27cases), type Ib (unilocular, size≥10cm, 17cases), type II (multilocular, sub-cavity near GI, 26cases), type III (multilocular, sub-cavity separated from GI, 20cases), type IV (multilocular, beyond inferior pole of kidney, 10cases). Treatment results were as follows, the technical success rate of first drainage (all type 100%), treatment success rate of EUS-TD alone (96%, 47%, 36%, 24%, 0%), treatment success rate of EUS-TD + DEN (100%, 94%, 50%, 41%, 0%),, treatment success rate of EUS-TD + DEN + Additional endoscopic drainage (100%, 94%, 100%, 94%, 44%), respectively.

The volume of sub-cavity requiring additional drainage was more than 65 m3 according to ROC curve. 3 cases in type IV were required hybrid approach. No cases required surgical treatment due to inadequate drainage. An early adverse

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Free Paper Section：HCV

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TREATMENT EFFICACY OF DIRECTLY ACTING ANTIVIRALS IN CHRONIC HEPATITIS C – TASL HCV REGISTRY (TACR) PROGRAM INTERIM REPORT Ming-Lung Yu1, Rong-Nan Chien2, Jia-Horng Kao3, Pei-Jer Chen3, Ding-Shinn Chen3, Yun-Fan Liaw2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan3

慢性 C 型肝炎小分子抗病毒藥物療效 台灣肝臟研究學會 TACR 聯盟期中報 告 余明隆1 簡榮南2 高嘉宏3 陳培哲3 陳定信3 廖運範2 高雄醫學大學附設中和紀念醫院肝膽胰內科1 林口長庚紀念醫院胃腸肝膽科系2 台大醫院內科部3 Background: Directly acting antivirals (DAAs) in the standard of care of chronic hepatitis C (CHC).

TASL HCV Registry (TACR) is the nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C in Taiwan. Until 2019, more than 35 hospitals have participated in TACR program.

Aims: The present study aimed to explore the interim report of TACR in terms of DAA treatment efficacy in CHC patients.

Methods: CHC patients who received DAAs and gave inform consents were registered on the TACR platform. The baseline characteristics, prior liver and non-liver related history DAA regimens, laboratory results, treatment course and outcome were recorded and input by site investigators accordingly. The primary objective

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was sustained virological response, which defined as undetectable HCV RNA 3 months after end-oftreatment (SVR12).

Results: A total of 15,017 CHC patients receiving DAAs have been registered in TACR system until May 2019. Of the 7,406 patients with available baseline characteristics, the mean age was 63.6 years. Female accounted for 43.8% of the population. The most common viral genotype is hepatitis C virus (HCV) genotype 1b (59.3%), followed by HCV-2 (32.6%). 3280 (44.5%) patients had liver cirrhosis, whereas 302 (6.8%) patients were with liver decompensation. 897 (12.1%) patients had hepatocellular carcinoma (HCC) history before DAAs treatment. 1915 (25.9%) patients were previous treatmentexperienced. The end-of-treatment (EOT) response was 98.9% (5,901/5,965). The SVR12 was 97.9% (5,299/5,410). Univariate analysis of factors associated with treatment failure included the use of daclatavir/asunaprevir and sofosbuvir/ ribavirin, DAA adherence＜80%, early treatment termination, liver decompensation, history of HCC. Logistic regression analysis revealed that factors independent associated with treatment failure was decompensated liver cirrhosis (odds ratio [OR]/95% confidence intervals [CI]: 2.3/1.24.7, P=0.017), history of HCC (OR/CI: 2.4/1.44.1, P=0.001), DAA adherence＜80% (OR/ CI: 11.7/2.3-58.6, P=0.003), early treatment termination (OR/CI: 10.6/2.1-53.8, P=0.005), and the use of daclatavir/asunaprevir (OR/CI: 4.5/2.39.0, P＜0.001) and sofosbuvir/ribavirin (OR/CI: 4.2/2.5-7.2, P＜0.001).

Conclusions: DAAs are highly effective in treating CHC patients in Taiwan. Further collaborative work is warranted regarding expanded cases, long-term outcome and the retreatment strategy for patients with DAAs failure through the platform.

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SVR RATES AND TOLERABILITY WITH DIRECT-ACTING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C-RELATED HEPATOCELLULAR CARCINOMA AND THOSE WITHOUT: A PROPENSITY SCORE MATCHED STUDY FROM THE ASIA LIVER CONSORTIUM (REAL-C) Chung-Feng Huang1, Eiichi Ogawa2, Ming-Lung Yu1, Mindie H. Nguyen3 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan2 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA3

(95.0%) groups. However, among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs. 93.7%, P=0.03). On multivariable regression analysis, prior treatment failure and active HCC were significantly associated with lower SVRs (OR 0.34, P=0.01), but not with treatment regimen.

Rates of treatment discontinuation, adverse effects, and death were also similar between the HCC and non-HCC groups.

Conclusions: DAA regimens studied were well tolerated and produced high and comparable effectiveness for those with inactive HCC and without HCC. Therefore, to increase HCV cure rates, we suggest delaying DAA therapy until HCC is treated or in remission.

Background: Since the introduction in East Asia of effective and safe direct-acting antivirals (DAAs) for hepatitis C virus (HCV), many patients in the historically difficult-to-treat population, such as those with hepatocellular carcinoma (HCC), have become treatment candidates.

Aims: The aim of the study was to evaluate DAA treatment outcomes in a large East Asian HCV/ HCC population compared to HCV/non-HCC patients.

Methods: This multicenter, multinational study included 6,081 patients (HCC, n=465; nonHCC, n=5,616) treated with interferon-free DAAs from several centers in Hong-Kong, Japan, South Korea, and Taiwan. We used propensity score matching (PSM) to match HCC and nonHCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin level.

Primary outcomes were treatment tolerability and sustained virological response (SVR).

Results: PSM of the entire study population yielded 436 matched pairs. Baseline characteristics of the HCC and non-HCC groups were similar after PSM. There were no statistically significant differences in overall SVR rates between the HCC (92.7%) and non-HCC

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COMPARISON OF REAL-TIME SHEAR WAVE ELASTOGRAPHY WITH APRI, FIB-4 AND FIBROSCAN® TO IDENTIFY LIVER FIBROSIS IN CHRONIC LIVER DISEASE Ming-Jeng Kuo, Lein-Ray Mo, Chun-Hsiang Wang, Kuo-Kwan Chang, Ray-Chang Lin Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan

剪力波速彈性影像在肝臟纖維化測量 的臨床驗證與 APRI、FIB-4 及纖維化 掃描儀的比較 郭明正 牟聯瑞 王俊雄 張國寛 林瑞昌 台南市立醫院肝膽腸胃科 Background: Shear wave elastography (SWE) was shown to be a non-invasive tool for quantification of liver fibrosis and had limited comparisons with other validated fibrosis tools.

Aims: The aim of this study was to assess the performances of SWE for the diagnosis of liver fibrosis.

Methods: We prospectively enrolled 169 patients who underwent liver biopsy from January 2016 to December 2017. Participants received measurement of Toshiba shear imaging (Aplio 500), fibrosis-4 (FIB-4) score, aspartate transaminase to platelet ratio index (APRI) and transient elastography (FibroScan). Areas under the receiver operating curves (AUROCs) were performed and compared for various degree of liver fibrosis.

Results: Liver fibrosis was METAVIR F1 in 18 (10.7%), F2 in 51 (30.2%), F3 in 58 (34.3%), and F4 in 42 (24.8%) patients (Table 1). SWE, FibroScan ® and FIB-4 correlated significantly with histological fibrosis score (r=0.42, p＜ 0.0001; r=0.46, p＜0.0001; r=0.24, p=0.0014, respectively) rather than APRI (r=0.11, p=0.14) (Table 2). The optimal cut-off values of SWE for significant fibrosis (＞F2), severe fibrosis (＞F3) and cirrhosis(F4) were 1.85, 2.06 and 2.30 m/s, respectively. AUROCs of SWE, Fibro Scan®, FIB4 and APRI were 0.70, 0.73, 0.68 and 0.67 for the diagnosis of significant fibrosis (＞F2); 0.83, 0.82, 0.74 and 0.68 for the diagnosis of severe fibrosis (＞F3); 0.84, 0.75, 0.74 and 0.68 for the diagnosis

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of cirrhosis (F4). SWE had a higher accuracy than APRI for the diagnosis of severe fibrosis (＞F3) (p=0.01), and a higher accuracy than APRI and FIB-4 for the diagnosis of cirrhosis (F4) (p=0.0009 and 0.01, respectively). No significant difference was observed for the diagnosis of significant fibrosis between SWE and biomarkers (Fig 1 A-C).

Conclusions: The performance of SWE is comparable to FibroScan® for the assessment of liver fibrosis in chronic liver disease. Comparing to biomarkers, the SWE showed a preference for the diagnosis of severe fibrosis and cirrhosis.

2019 TDDW

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THE EFFICACY OF SOFOSBUVIRLEDIPASVIR WITH/WITHOUT RBV FOR PATIENTS WITH HCV GENOTYPE 2 INFECTION ‒ A REALWORLD EXPERIENCE OF SIX HOSPITALS IN TAIWAN Po-Yueh Chen1, Kuo-Chih Tseng2,3, Ching-Chu Lo4, Jyh-Joy Chen5, Chao-Hung Hung6, Shih-Jer Hsu7, Chi-Yi Chen1 Division of Gastroenterology and Hepatology, Department of Internal medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan1 Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation2 School of Medicine, Tzuchi University, Hualien, Taiwan3 Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan4 Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan5 Division of Hepato-Gastroenterology, Department of Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan6 Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan7

Sofosbuvir/Ledipasvir 在基因型 2 型 慢性 C 型肝炎患者的治療成效—雲嘉 南六院的經驗 陳柏岳1 曾國枝2,3 羅清池4 陳志州5 洪肇宏6 徐士哲7 陳啟益1 嘉義基督教醫院1 大林慈濟醫院2 慈濟醫學院3 天主教中華聖母修女會醫療財團法人天主教聖馬 爾定醫院4 柳營奇美醫院5 嘉義長庚紀念醫院6 國立臺灣大學醫學院附設醫院雲林分院7 Background: Sofosbuvir-ledipasvir has been proved to achieve high rate of sustained viral response for treatment of patients with HCV genotype 1 infection worldwide. As for patients

with HCV genotype 2 infection, sofosbuvir combined with weight-based ribavirin was recommended based on earlier studies. However, the rate of sustained viral response was lower than 90% in several large cohorts. In Asia-Pacific region, the pooled analysis of three clinical studies in Taiwan, Japan and New Zeeland, respectively, revealed that using sofosbuvir-ledipasvir for patients with HCV genotype 2 infection without decompensated cirrhosis could result in more than 95% of sustained viral response. Based on these results, sofosbuvir-ledipasvir has been reimbursed for treatment of patients with HCV genotype 2 infection since Oct 2018 in Taiwan.

Aims: The aim of our study is to evaluate the efficacy and safety of sofosbuvir-ledipasvir for patients with HCV genotype 2 infection.

Methods: A total of 67 patients with pure or mixed HCV genotype 2 infection, who were treated by sofosbuvir-ledipasvir±RBV since Oct 2018, were enrolled from six hospitals in the middlearea of Taiwan. Baseline clinical characteristics, viral response, and serial changes of estimated glomerular filtration rate (eGFR) were assessed.

Adverse effects were also recorded in this study.

Results: Among 67 patients, the mean age was 67.5±11.6 years old and 43 patients (64.2%) were female. 36 patients (53.7%) had cirrhosis and none of them had decompensation. Mean HCV RNA was 2.51 MIU/ml and 13 (19.4%) patients has mixed genotypic infection (Table 1). The overall SVR12 rate of sofosbuvir/ ledipasvir±RBV was 100% for patients with HCV GT2 or mixed type infection. The SVR12 rate was not influenced by genotypes, age, experience of interferon treatment, ribavirin use or fibrosis stage.

There was no significant alternation of estimated glomerular filtration rate from baseline to SVR12, regardless of baseline values (＞60 or＜60 ml/ min/1.73m2). The frequency of any adverse effect was 22.4% (15/67), and fatigue was the most common (Table 2). None of them had interruption or discontinuity of treatment.

Conclusions: For patients with pure or mixed HCV genotype 2 infection without decompensated cirrhosis, sofosbuvir-ledipasvir±RBV could achieve excellent SVR12 to 100% with modest adverse effects and good tolerability.

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SUSTAINED AUGMENTATION OF CENTRAL ARTERIAL STIFFNESS FOLLOWING VIRAL CLEARANCE

BY DIRECT ACTING ANTIVIRALS IN CHRONIC HEPATITIS C Pin-Nan Cheng1, Ju-Yi Chen2, Hung-Chih Chiu1, Liang-Min Tsai2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan2

直接作用抗病毒藥物清除 C 肝病毒後 伴隨持續增加中央動脈血管硬度 鄭斌男1 陳儒逸2 邱宏智1 蔡良敏2 國立成功大學醫學院附設醫院內科部消化內科1 國立成功大學醫學院附設醫院內科部心臟內科2 Background: Chronic hepatitis C virus (HCV) infection is significantly associated with the risk of cardiovascular diseases. Although direct acting antivirals (DAA) results in a rapid eradication of HCV, the long-term impact on arterial stiffness and associated parameters remains unclear.

Aims: This study aimed to evaluate the changes in parameters of central artery from before treatment, to sustained virological response, to one year after viral clearance.

Methods: Chronic HCV patients receiving DAA treatment were prospectively enrolled from February 2017 to October 2017. Detail medical history and comorbidities were collected.

Lipid profiles, liver stiffness by transient elastography, and central blood pressures by pulse wave analysis of the brachial artery by cuff sphygmomanometry were measured before treatment, at viral clearance, and at one year following viral clearance. Augmentation index (AIx), a parameter of aortic stiffness, was calculated as the ratio of augmentation pressure to central pulse pressure.

Results: Of the 58 chronic HCV patients enrolled, all achieved viral clearance. Cholesterol, low-

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density lipoprotein (LDL), and triglyceride/ high-density lipoprotein (TG/HDL) significantly increased at viral clearance and persisted at one year (all p＜0.001). In parallel with lipid changes, the AIx was also significantly elevated at viral clearance and at one year later (p＜0.001). The changes in AIx remained significant only for those with a change from baseline in either LDL (p＜ 0.01) or TG/HDL (p＜0.001).

Conclusions: The central arterial stiffness and lipid profiles in chronic HCV patients were worse immediately after viral eradication by DAA treatment and persisted. Worsening of lipid profiles after DAA treatment contributed to central arterial stiffness in these patients and persisted long term.

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Section：LGI

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SELF-EXPANDABLE METALLIC STENT FOR BOWEL OBSTRUCTION CAUSED BY COLORECTAL ADENOCARCINOMA—A 10-YEAR EXPERIENCE OF SINGLE MEDICAL CENTER Chi Shine Wang1,2, Hsu-Heng Yen1 Division of Gastroenterology Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan1 Division of Gastroenterology Hepatology, Changhua Hospital Ministry of Health and Welfare, Changhua, Taiwan2

自擴式金屬支架應用於大腸癌腸阻塞 —單一醫學中心 10 年的經驗 王棋新1,2 顏旭亨1 彰化基督教醫院胃腸肝膽科1 衛生福利部彰化醫院2 Background: Self-expandable metallic stents (SEMSs) were extensively applied in various condition currently such as benign or malignant stricture. The study evaluated the 10-year period of SEMs deployment for colorectal cancer. Covered or uncovered stents was used under the judgement by operator during the procedure proceeded. Covered stent was used for the evidence of fistula formation or high risk of perforation during the stent was deployed.

The main purpose for SEMs was aimed at the patency of obstructive tracts, make bridge to surgical resection and improvement of quality of life in patients with end-staged malignancy.

Technical and clinical success rate as primary endpoints were analyzed. Complications including perforation, bleeding, migration and re-obstruction as second endpoints were investigated.

Aims: The study aimed at the SEMS applied in the condition which colorectal cancer led to colonic obstruction. We analyzed the outcome of survival and complication rates of SEMS deployment.

Methods: The study investigated the population who had colorectal cancer with obstruction received SEMS retrospectively. Since Aug, 2010, 134 patients were analyzed with the baseline characteristics including age, gender and comorbidities and laboratory data such as Carcinoembryonic antigen, albumin, blood urea nitrogen, creatinine and electrolytes such

as potassium, sodium and calcium (Table 1).

The SEMS was used either Nitis or Wallflex (produced by Tae Woon or Boston, respectively).

The complications such as perforation, bleeding, migration and re-obstruction are stratified as early, delayed and late and analyzed these data.

The definitions of early, delayed and late are according to the time of complications developed, within 72 hours, 72 hours to 1 month and more than 1 month, respectively.

Results: In our study, 82 patient received the SEMS deployment as palliative treatment, 52 patient received SEMS as a bridge to surgery.

The mean length of hospitalization for elective deployment of SEMS is 11 days and the one for emergency is 9 days, it seems no statistical significance between these two groups. The locations of tumor developed were also analyzed, revealing the most common site led to obstruction is sigmoid colon, accounting for 56.7% (76/134).

The technical and clinical success rate are 94.7% (127/134) and 91% (122/134), respectively.

There is no significant difference between male and female group. The complete obstruction is the main reason to cause the failure of stent deployment. Subsequently, the patients who failed to deploy SEMS were received surgical intervention (7), hospice care (4) and second attempt (1). The 1-year survival between palliative (30/82, 36.5%) and bridge to surgery (48/51, 94.1%) group is dramatically significant, demonstrated in Figure 1. The most common early complication is perforation, accounting for 3.7% (5/134). Migration is also another common condition in the group of early complication (4/134, 2.9%). The most common complication in delayed group are perforation and re-obstruction, accounting for 2.2% (3/134; 3/134). Reobstruction and migration are the majority of late complications, accounting for 4.4% (6/134) and 2.9% (4/134). The data is demonstrated in Figure 2.

Conclusions: SEMS is extensively applied for the obstruction by malignancy, no matter how is for palliative treatment or bridge to surgery. The success rate is high and complications rate is low. In the retrospective study, the most common early complication is perforation and it needed the prompt surgical intervention. Re-obstruction is the common late complication, the main treatment for the condition is hospice care. In conclusion, SEMS deployment for malignant obstruction is a relatively safe and highly successful method to make bridge to surgery or palliation.

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PRO-APOPTOTIC EFFECT OF HAEM OXYGENASE-1 IN HUMAN COLORECTAL CARCINOMA CELLS VIA ENDOPLASMIC RETICULAR STRESS Ming-Shun Wu1,2, Chun Nan Chen1, Shi-Bin Huang1, Fat-Moon Suk1,2, Gi-Shih Lien1,2, Yen-Chou Chen3 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan3

血鐵質氧化酶－透過內質網壓力造成 大腸癌細胞凋亡 吳明順1,2 陳俊男1 黃世斌1 粟發滿1,2 連吉時1,2 陳彥州3 臺北醫學大學—萬芳醫院消化系內科1 臺北醫學大學醫學院消化內科學科2 臺北醫學大學醫學院醫學科學研究所3 Background: Colorectal cancer (CRC) is one of the leading diagnosed cancers with high mortality, and remains a significant global health problem.

Many chemotherapeutic agents, such as taxol and carboplatin, are used to treat CRC; however, there are side effects with chemotherapy that are associated with high mortality and local recurrence at least in part through ROS production. In humans, haem-iron is more bioavailable than non-haem-iron, and unabsorbed haem reaches colon epithelial cells.15 Previous studies showed that haem is able to irritate the epithelium of the colon as indicated by mild diarrhoea. Feeding haem resulted in significantly increased proliferation of colonic mucosa of rats.

This indicates the positive correlation between haem and colon carcinogenesis. HO-1 induction was shown to metabolize haem, accompanied by producing four byproducts: CO, ferric ion, BV and BR. Aims: The effects of HO-1 overexpression on

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CRC treatment and the roles that ROS and their byproducts play in the process are still unclear.

Methods: DNA fragmentation assay, Detection of hypodiploid cells by CoPP, Measurement of ROS generation.

Results: In the presence of stimulation by cobalt protoporphyrin (CoPP), an HO-1 inducer, apoptotic characteristics were observed, including DNA laddering, hypodiploid cells, and cleavages of caspase (Casp)-3 and poly(ADP) ribose polymerase (PARP) proteins in human colon carcinoma COLO205, HCT-15, LOVO and HT-29 cells in serum-free (SF) conditions with increased HO-1, but not heat shock protein 70 (HSP70) or HSP90. The addition of 10% foetal bovine serum (FBS) or 1% bovine serum albumin accordingly inhibited CoPP-induced apoptosis and HO-1 protein expression in human colon cancer cells. CoPP-induced apoptosis of colon cancer cells was prevented by the addition of the pan-caspase inhibitor, Z-VAD-FMK (VAD), and the Casp-3 inhibitor, Z-DEVD-FMK (DEVD).

N-Acetyl cysteine inhibited reactive oxygen species-generated H2 O2 -induced cell death with reduced intracellular peroxide production, but did not affect CoPP-induced apoptosis in human colorectal carcinoma (CRC) cells. Two CoPP analogs, ferric protoporphyrin and tin protoporphyrin, did not affect the viability of human CRC cells or HO-1 expression by those cells, and knockdown of HO-1 protein expression

by HO-1 small interfering (si)RNA reversed the cytotoxic effect elicited by CoPP. Furthermore, the carbon monoxide (CO) donor, CORM, but not FeSO4 or biliverdin, induced DNA ladders, and cleavage of Casp-3 and PARP proteins in human CRC cells. Increased phosphorylated levels of the endoplasmic reticular (ER) stress proteins, protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2α (eIF2α) by CORM and CoPP were identified, and the addition of the PERK inhibitor, GSK2606414, inhibited CORM- and CoPP-induced apoptosis. Increased GRP78 level and formation of the HO-1/GRP78 complex were detected in CORM- and CoPP-treated human CRC cells.

Conclusions: A pro-apoptotic role of HO-1 against the viability of human CRC cells via induction of CO and ER stress was firstly demonstrated in this study.

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RISK OF COLONOSCOPYRELATED COMPLICATIONS IN A POPULATION-BASED FECAL IMMUNOCHEMICAL TEST SCREENING PROGRAM

Wen-Feng Hsu, Li-Chun Chang, Ming-Shiang Wu, Han-Mo Chiu Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

with ordinary colonoscopy, FIT colonoscopy and the execution of treatment procedures were significantly associated with higher odds of having complications (aOR=2.33, 95% CI, 2.20–2.48; and aOR=2.74, 95% CI, 2.56–2.93, respectively).

Conclusions: Significant bleeding, one of severe colonoscopy-related complications, is two times greater with FIT colonoscopy than ordinary colonoscopy.

以群眾為基礎的糞便免疫化學法大腸 癌篩檢計畫中大腸鏡相關併發症之風 險 許文峰 張立群 吳明賢 邱瀚模 國立臺灣大學醫學院附設醫院內科部 Background: The likelihood of having advanced neoplasm or synchronous neoplasm is much higher in fecal immunochemical test (FIT)-positive subjects than in the general population.

Aims: This study investigated the magnitude of colonoscopy-related complications in FIT-positive patients.

Methods: Patients who received colonoscopy after positive FIT (FIT colonoscopy) or ordinary colonoscopy from 2010 to 2014 were identified in the Taiwanese Colorectal Cancer (CRC) Screening Program Database and National Health Insurance Database, respectively. Significant complications included significant bleeding, perforation, and cardiopulmonary events within 14 days of colonoscopy. The number of events per 1000 procedures was used to quantify the complication magnitude. Multivariate analysis was conducted to compare the risks between FIT colonoscopy and ordinary colonoscopy, adjusting for major confounding variables.

Results: A total of 319,114 FIT colonoscopies (214,955 subjects), including confirmatory or clearing procedures, and 850,113 ordinary colonoscopies (60,1942 subjects) were included.

Of patients who received FIT colonoscopy, 53.6% were male, and the mean age was 60.2 years.

Among FIT colonoscopies performed, 51,242 (16.1%) involved biopsy and 94,172 (29.5%) ; 95% involved polypectomy, with 2125 (6.7 CI, 6.4–6.9 ) experiencing significant bleeding, 276 (0.9 ; 95% CI, 0.8–1.0 ) experiencing perforation, and 10 (0.03 ; 95% CI, 0.01– 0.05 ) experiencing cardiopulmonary events within 14 days after colonoscopy. Compared

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MUTATION ANALYSIS IN COLON POLYPS AND COLORECTAL CANCER IN CENTRAL TAIWAN Ho-Li Wang1, Ching-Pin Lin1,2 Division of Gastroenterology, Department of internal medicine, Chung Shan Medical University Hospital, Taichung, Taiwan1 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan2

中台灣大腸息肉及大腸直腸癌之 BRAF 突變分析 王賀立1 林敬斌1,2 中山醫學大學附設醫院消化內科1 中山醫學大學微生物免疫研究所2 Background: Colorectal cancer (CRC) is one of the most common cancers and usually causes by the mutations in the epithelial cells of the gastrointestinal surfaces resulting in hyperactivity of the signaling pathways and finally transforms these cells into the adenomatous polyps. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/ threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). Accumulation of the inherited or acquired mutations transits the adenomatous polyps to malignancy. Recently, the serrated pathway to colorectal cancer, in which serrated polyps develop into cancers, has received much attention as an alternative pathway in colorectal carcinogenesis. Hyperplastic polyps (HP) share some histologic and molecular characteristics with sessile serrated adenomas (SSA), but it is unclear whether SSA is derived from HPs or whether they develop by a different pathogenetic pathway.

Aims: The purpose of this study was to evaluate the molecular features of HPs and SSA in Central Taiwan.

Methods: We used FemtoPath BRAF Exon 15 Primer Set (HongJing Biotech.) to detect BRAF mutation for 84 specimens and resulting with highly frequency mutation rate in polyps. We are revealed the genetic correlation between HPs and SSA. A feature of polyps is the identification of BRAF mutations that provide a genetic testing as a biomarker in Chung Shan Medical University

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Hospital.

Results: We analyzed total 49 patients with 44 polyps and 40 cancer tissues for the exon 15 of BRAF gene mutation. The molecular and clinical characteristics of each sample are summarized in table 1-4. The driver mutation types of BRAF gene included V600E, V600M and V600V. In this study, result showed 4 polyps were mutant type (9.1%) and wild type with 40 polyps (90.9%). In addition, there were 7 colon cances with BRAF gene mutation (17.5%) and 33 colon cancers were wild type (82.5%).

Conclusions: In summary, higher percentage of BRAF gene mutation noted in colon cancer group compared with benign polyps group, and sample taken from right colon also had higher risk of BRAF gene mutation.

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RISK FACTORS DETERMINING THE DETECTION OF ADVANCED COLORECTAL NEOPLASIA IN PATIENTS WITH NEGATIVE FECAL IMMUNOCHEMICAL TEST Wei-Chun Cheng1,2, Wei-Ying Chen1, Po-Jun Chen1, Meng-Ying Lin1, Hsiu-Chi Cheng1, Wei-Lun Chang1, Chung-Tai Wu1, Yu-Ching Tsai1,2, Er-Hsiang Yang1, Hsin-Yu Kuo1, Bor-Shyang Sheu1 Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Gastroenterology Department, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan2

免疫生化法糞便潛血反應陰性大腸直 腸腫瘤患者之風險因子分析 鄭維鈞1,2 陳威穎1 陳柏潤1 林孟穎1 鄭修琦1 張維倫1 吳忠泰1 蔡郁清1,2 楊貳翔1 郭欣瑜1 許博翔1 國立成功大學醫學院附設醫院內科部1 衛生福利部臺南醫院胃腸內科2

analysis, comprising 84 patients with a positive fecal immunochemical test (equal or more than 30 ug Hb/g feces) and 1997 patients with a negative fecal immunochemical test, within 6 months before colonoscopy. In patients with positive and negative fecal immunochemical test, 47.6% and 33.7% were detected with colorectal adenoma, while 20.2% and 13.7% were detected with advanced colorectal neoplasia (defined as adenoma with size equal to or more than 1 cm in size, with villous component in pathology with high grade dysplasia, or adenocarcinoma), respectively. The Univariate and Multivariate logistic regression analyses showed that older age, smoking history and metabolic syndrome were risk factors for the detection of advanced colorectal neoplasia in patients with a negative fecal immunochemical test. Combinations of these three factors yielded 68.4% and 22.8% detection rate of colorectal adenoma and advanced colorectal neoplasia, respectively. The detection rates of this risk factor combination were superior to those in patients with a positive fecal immunochemical test.

Conclusions: For patients with a negative fecal immunochemical test, colonoscopy screening should be considered for those who are older than 50 years, with a history of smoking and metabolic syndrome.

Background: Fecal immunochemical test (FIT) for colorectal cancer screening is currently the standard strategy in Taiwan. With biennial FIT tests for those aged of 50-75 years for colonoscopy, the goal of shifting cancer to earlier stage and decreasing cancer-related mortality has been achieved. However, advanced colorectal adenoma has been shown in patients with negative fecal immunochemical test, accounting for 95 % of screened populations.

Aims: The study aimed to investigate risk factors associated with advanced colorectal neoplasia in patients with negative fecal immunochemical test.

Methods: Patients who had a fecal immunochemical test and then received colonoscopy within 6 months from 2015/7 to 2016/12 in the Health Management Center of National Cheng Kung University Hospital were enrolled. Those who were less than 20 years old, with a history of malignancy or inflammatory bowel disease, or had poor bowel preparation in colonoscopy were excluded.

Results: 2081 cases were included in this

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Sectionďź&#x161;HBV

â&#x2018;Ş

HIGH RISK OF CLINICAL RELAPSE IN HBV-INFECTED PATIENTS AFTER STOPPING PROPHYLACTIC ANTIVIRAL THERAPY FOR RITUXIMAB-CONTAINING CHEMOTHERAPY Wei-Yuan Chang1, Yen-Cheng Chiu10, Fang-Wei Chiu11, Tai-Chung Tseng1,2, Pin-Nan Cheng10, Hong-Chi Chiu10, Sheng-Shun Yang11,12,13,14, Chun-Jen Liu1,2,5, Tung-Hung Su1,2, Hung-Chih Yang1,5,6, Chen-Hua Liu1,2, Pei-Jer Chen1,2,5, Ding-Shinn Chen7, Jia-Horng Kao1,2,3,5 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan3 Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan5 Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan6 Genomics Research Center, Academia Sinica, Taiwan7 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan8 Institute of Statistical Science, Academia Sinica, Taiwan9 Department of gastroenterology and hepatology, National Cheng Kung University Hospital, Tainan, Taiwan10 Division of Gastroenterology & Hepatology, Department of Internal Medicine,Taichung Veterans General Hospital, Taichung, Taiwan11 School of Medicine, Chung Shan Medical University, Taichung, Taiwan12 Rong Hsing Research Center for Translational

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Medicine, National Chung Hsing University, Taichung, Taiwan13 Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan14 Background: Prophylaxis treatment with nucleos(t)ide analogue (NA) is mandatory for hepatitis B surface (HBsAg)-positive patients receiving chemotherapy containing rituximab, which is a potent B cell-depleting agent. However, little is known about whether withdrawal of prophylactic NA is associated with a high risk of clinical relapse after completing rituximabcontaining chemotherapy.

Aims: To address these issues, we conducted this study to determine the patterns and predictors of relapse and the outcomes after discontinuation of a prophylactic NUC therapy for Rituximabcontaining cytotoxic therapy for HBV carriers with a hematological mali Methods: We retrospectively analyzed 72 HBsAg carriers with hematological malignancies who received rituximab-containing chemotherapy. All of them received either prophylactic entecavir or tenofovir therapy, which had been extended for 6 months or more after discontinuation of the antitumor therapy (extension therapy). We explored their risks of HBV reactivation, clinical relapse and liver decompensation after stopping NA. Results: There were 30 (41.67 %) patients developing clinical reactivation and most of events occurred within 1 year (24/30; 80 %).

Our data showed that higher baseline HBV viral load (>2000 vs <2000 IU/ml) before rituximab administration, but not duration of extension therapy (6-12 months vs >12 months), was associated with an increased risk clinical relapse (HR: 3.91, 95% CI: 1.82-8.39, p=0.001). To be noted, 14 (19.44%) patients developed Hepatic failure after stopping NUC treatment and three of them had a low viral load before anti-viral treatment.

Conclusions: In conclusion, there are high risks of clinical relapse or liver failure after stopping prophylactic NA therapy in patients receiving rituximab-containing chemotherapy. A higher HBV viral load, but not extended NA treatment duration, is associated with risks of these liverrelated adverse events.

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HIGH LEVEL OF HEPATITIS B CORE-RELATED ANTIGEN ASSOCIATED WITH INCREASED RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HBV INFECTION OF INTERMEDIATE VIRAL LOAD Tai-Chung Tseng1,2, Chun-Jen Liu1,2,5, Chun-Ming Hong1,4, Tung-Hung Su1,2, Wan-Ting Yang2, Chi-Ling Chen5, Hung-Chih Yang1,5,6, Chen-Hua Liu1,2, Pei-Jer Chen1,2,5, Ding-Shinn Chen7, Jia-Horng Kao1,2,3,5 Division of Gastroenterology, Department of Internal Medicine ,National Taiwan University Hospital,Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.2 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan3 Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan5 Department of Microbiology, National Taiwan University College of Medicine Taipei, Taiwan6 Genomics Research Center ,Academia Sinica, Taiwan7

B 型肝炎病毒核心相關抗原對於中病毒 量之慢性 B 型肝炎病患，可有效區分 其肝癌風險 曾岱宗1,2 劉俊人1,2,5 洪俊銘1,4 蘇東弘1,2 楊菀婷2 陳祈玲5 楊宏志1,5,6 劉振驊1,2 陳培哲1,2,5 陳定信7 高嘉宏1,2,3,5 國立台灣大學醫學院附設醫院內科部胃腸科1 國立台灣大學醫學院附設醫院肝炎研究中心2 國立台灣大學醫學院附設醫院醫學研究部3 國立台灣大學醫學院附設醫院內科部4 國立台灣大學醫學院臨床醫學研究所5 國立台灣大學醫學院微生物研究所6 中央研究院基因體研究中心7

Background: Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC). Serum levels of HB corerelated antigen (HBcrAg) have been associated with active replication of HBV. Aims: We investigated whether HBcrAg levels associate with development of HCC, especially in patients who do not require antiviral treatment.

Methods: We collected data from 2666 adults positive for hepatitis B surface antigen (HBsAg), infected with HBV genotypes B or C and without liver cirrhosis, who had a long-term follow-up at the National Taiwan University Hospital, from 1985 through 2000. All the patients did not have antiviral treatment during the follow-up. Baseline levels of HBV DNA, HBsAg, and HBcrAg were determined retrospectively and participants were followed for a mean time of 15.95 years. The primary endpoint was association between serum level of HBcrAg and HCC development.

Results: In the entire cohort, 209 patients developed HCC (incidence rate, 4.91 cases/1000 person-years). We found a positive association between baseline level of HBcrAg and HCC development; HBcrAg level was an independent risk factor in multivariable analysis. In the subgroup of hepatitis B e antigen-negative patients with HBV DNA levels from 2000 to 19,999 IU/mL (intermediate viral load, IVL) and normal levels of alanine aminotransferase, HBcrAg levels of 10 KU/mL or more identified patients at increased risk of HCC (hazard ratio, 4.89; 95% CI, 2.18–10.93). Patients with an IVL and high levels of HBcrAg had a risk for HCC risk that did not differ significantly from that of patients with a high viral load (≥20,000 IU/mL). Patients with an IVL but a low level of HBcrAg had a low risk of HCC with an annual incidence rate of 0.10% (95% CI: 0.04%-0.24%).

Conclusions: In a long-term follow-up study of 2666 patients with chronic HBV infection (genotypes B or C), level of HBcrAg is an independent risk factor of HCC. Moreover, HBcrAg level of 10 KU/mL identifies patients with an IVL who are at high risk for HCC.

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HEPATITIS B VIRUS RELAPSE AFTER CESSATION OF TENOFOVIR OR ENTECAVIR THERAPY FOR CHRONIC HEPATITIS B – AN MIDTERM ANALYSIS OF A PROSPECTIVE COHORT STUDY OF THE CENTRAL TAIWAN RESEARCH ALLIANCE FOR LIVER DISEASES (CENTRAL) GROUP Wei-Wen Su1, Chih-Sheng Wu2, Cheng-Yuan Peng3, Teng-Yu Lee4, Shih-Tien Chen5, Sheng-Li Yan6, Jen-Chieh Huang7, Chun-Che Lin8, Tsung-Ming Chen9, Kuan-Fu Liao10 Changhua Christian Hospital, Changhua, Taiwan1 Show Chwan Memorial Hospital, Changhua, Taiwan2 China Medical University Hospital, Taichung, Taiwan3 Taichung Veterans General Hospital, Taichung, Taiwan4 Chang-Hua Hospital, Ministry of Health and Welfare, Changhua, Taiwan5 Show Chwan Memorial Hospital, Chang Bing Branch, Changhua, Taiwan6 Cheng Ching General Hospital, Chung Kang Branch, Taichung, Taiwan7 Chung Shan Medical University Hospital, Taichung, Taiwan8 Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan9 Taichung Tzu Chi Hospital, Taichung, Taiwan10

Tenofovir 或 Entecavir 治療慢性 B 型 肝炎停藥後的病毒復發—台灣中區肝病 研究聯盟前瞻性世代研究的期中分析 蘇維文1 吳志昇2 彭成元3 李騰裕4 陳詩典5 顏聖烈6 黃仁杰7 林俊哲8 陳宗勉9 廖光福10 彰化基督教醫院1 秀傳紀念醫院2 中國醫藥大學附設醫院3 臺中榮民總醫院4 衛生福利部彰化醫院5 彰濱秀傳紀念醫院6 澄清綜合醫院中港分院7

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中山醫學大學附設醫院8 童綜合醫院9 台中慈濟醫院10 Background: The relapse of hepatitis B virus (HBV) remains an important issue after cessation of nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB).

Aims: The aim of this study was to investigate the risk factors of HBV relapse after stopping tenofovir disoproxil fumarate (TDF) or entecavir (ETV) therapy.

Methods: In total, 10 hospitals in central Taiwan joined this prospective cohort study. CHB patients, who discontinued TDF or ETV therapy according to the NA stopping rules of the Asian Pacific Association for the Study of the Liver (APASL) guidelines, were prospectively recruited since 29 January 2015. Patients with liver cirrhosis, active malignancies, hepatitis C virus, hepatitis D virus or human immunodeficiency virus coinfection, liver transplantation history, immune disorders, a history of NA therapy other than TDF or ETV, or a follow-up period of less than 12 weeks were excluded. During the follow-up period, serum alanine aminotransferase (ALT), HBV DNA, and quantitative hepatitis B surface antigen (qHBsAg) levels were measured every 3 months, and the above-mentioned tests were checked more frequently if clinically indicated. Virologic relapse (VR) was defined as a serum HBV DNA level of＞ 2000 IU/mL and clinical relapse (CR) was defined as a serum HBV DNA level of＞2000 IU/mL with an ALT level of＞2X upper limit of normal. Both cumulative incidences of and hazard ratios (HRs) for the predictors of HBV relapse were analyzed.

Results: As of 30 April 2019, 225 patients (71 HBeAg-positive and 154 HBeAg-negative prior to NA therapy) had been enrolled for this analysis (132 TDF and 93 ETV users), with the median duration of prior NA therapy of 3.0 years (25–75% interquartile ranges [IRQs]: 2.9-3.1). The median follow-up period was 1.1 years (25–75% IRQs: 0.6-2.0). The 2-year cumulative incidence of VR was 83.7% (95% confidence interval [CI]: 77.689.8), and the 2-year cumulative incidence of CR was 49.7% (95% CI: 41.8-57.6). Among patients with CR, 26 (11.6%) patients experienced ALT elevations＞500 IU/L, and NA therapy was restarted in 78 (34.7%) patients. Six (2.7%) patients experienced liver decompensation.

HBsAg loss occurred in 6 (2.7%) patients. In

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multivariable analysis, qHBsAg＜300 IU/mL at the end of therapy was independently associated with a reduced risk in VR (HR 0.64, 95% CI: 0.43-0.95; P＜0.05) and CR (HR 0.59, 95% CI: 0.35-0.99; P ＜0.05). Moreover, lower the qHBsAg level was, lower the rate of VR or CR was. TDF use was not associated with a higher CR rate (HR 1.29, 95% CI: 0.85-1.94; P=0.23) compared to ETV use.

Conclusions: HBV relapse is common after cessation of NA therapy, and qHBsAg＜300 IU/ mL at the end of NA therapy can be a useful marker to predict a lower rate in VR or CR.

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TENOFOVIR VERSUS ENTECAVIR FOR HEPATOCELLULAR CARCINOMA PREVENTION IN AN INTERNATIONAL CONSORTIUM OF CHRONIC HEPATITIS B Yao-Chun Hsu1, Grace Lai-Hung Wong2, Chien-Hung Chen3, Cheng-Yuan Peng4, Ming-Lung Yu5, Mindie Nguyen6 E-Da Hospital/I-Shou University, Kaohsiung, Taiwan1 The Chinese University of Hong Kong, Hong Kong2 Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan3 China Medical University Hospital, Taichung, Taiwan4 Kaohsiung Medical University, Kaohsiung, Taiwan5 Stanford University Medical Center, Stanford, CA, USA6

在 REAL-B 國 際 研 究 聯 盟 中 比 較 Tenofovir 和 Entecavir 預防肝癌發生 的效果 許耀峻1 黃麗虹2 陳建宏3 彭成元4 余明隆5 Mindie Nguyen6 義大醫院/ 義守大學1 香港中文大學2 高雄長庚紀念醫院與長庚大學醫學院3 中國醫藥大學附設醫院4 高雄醫學大學5 美國史丹佛大學醫學中心6 Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).

Aims: We aimed to clarify the association between antiviral therapy using TDF versus ETV and the risk of incident HCC in patients with CHB. Methods: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or

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TDF monotherapy. Those who developed HCC before antiviral treatment or within one year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the two treatment cohorts. A total of 5,537 patients were eligible (n=4,837 received ETV and n=700 received TDF) and observed for HCC occurrence until December 23, 2018. Prior to PSM, the TDF cohort was significantly younger and had generally less advanced diseases.

Results: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45; 95% CI, 0.26~0.79; P=0.005). The multivariable analysis, however, found that the association between TDF and HCC no longer existed (SHR, 0.81; 95% CI, 0.42~1.56; P=0.52) after adjustment for age, sex, country, albumin, platelet, α-fetoprotein, cirrhosis, and diabetes mellitus. Furthermore, the PSM analysis (n=1,040) found no betweencohort differences in HCC incidences (P=0.51) and no association between regimens (TDF or ETV) and HCC risk in the multivariable-adjusted analysis (adjusted SHR, 0.89; 95% CI, 0.41~1.92; P=0.77).

Conclusions: TDF and ETV did not significantly differ in the prevention of HCC in CHB patients.

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THE OPTIMAL DURATION OF CONSOLIDATION TREATMENT PRIOR TO CESSATION OF NUC THERAPY IN HBEAG-NEGATIVE PATIENTS Wen-Juei Jeng1,2, Yi-Cheng Chen1,2, I-Shyan Sheen1,2, Rong-Nang Chien1,2,3, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan3

e 抗原陰性患者停藥前最適合鞏固治療 時間長度的探討 鄭文睿1,2 陳益程1,2 沈一嫻1,2 簡榮南1,2,3 廖運範2,3 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 林口長庚紀念醫院肝臟研究中心3 Background: In finite Nuc therapy in HBeAg negative chronic hepatitis B (CHB) patients, the consolidation duration proposed by APASL stopping rule is ≥ 1 year. However, the duration proposed in Western studies and EASL guidelines was 2-3 years.

Aims: To investigate the optimal length of consolidation treatment in terms of 1-year clinical relapse (CR: HBV DNA ≥ 2000 IU/ml + ALT ≥ 2X ULN) rate in a large number of patients.

Methods: HBeAg negative CHB patients received monotherapy with Nuc and stop therapy

by APASL guidelines (undetectable HBV DNA for more than 1 year) and had been followedup ≥ 1 year were recruited. The 1-year CR rate was compared among patients with consolidation therapy of 1-2 year vs. 2-3 and ≥ 3 years.

Baseline demographic features, Nuc used, HBV DNA, qHBsAg level, treatment duration, ontreatment early rapid qHBsAg decline, qHBsAg reduction＞1 log10IU/ml during treatment, time to ALT normalization, time to undetectable DNA, consolidation treatment duration, end-of-treatment (EOT) qHBsAg were compared between patients with and without 1-year CR. Logistic regression

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Section：Pancreas / Biliary was applied to investigate the predictors for 1-year clinical relapse.

Results: A total of 902 patients were included, 719 were treated with entecavir (ETV), 84.% were males, mean age was 52.7 years, 42.7% were cirrhotics and 54.3% were treatment experienced. During 1-year follow-up, 72.4% patients encountered virologic relapse and 44.6% CR. Multivariate analysis showed older age [aOR: 1.02 (1.01-1.04), P=0.0013], cirrhotic [aOR: 1.35 (1.02-1.79), P=0.0375], ETV therapy [ETV vs. non-ETV: aOR: 0.49 (0.35-0.68), P＜0.0001], ALT normalization＞6 months [aOR: 1.81 (1.282.55, P=0.0008) and EOT qHBsAg level [aOR: 1.54 (1.21-1.95), P=0.0004] were independent predictors for off-Nuc 1-year CR. The duration of consolidation therapy was not a factors for relapse [1-2 year as referent, 2-3 years: crude OR (95% CI): 1.01 (0.77-1.33) P=0.9478, ≥ 3 years: 0.96 (0.57-1.61) P=0.8716 respectively] (Figure) nor duration of total treatment [＜2 years as referent, 2-3, 3-4, ≥ 4: crude OR (95% CI): 0.98 (0.641.48), P=0.9075, 1.43 (0.94-2.18), P=0.0927, 0.8 (0.41-1.55), P=0.5066, respectively].

Conclusions: The results have demonstrated that a consolidation duration＞1 year was not inferior to those＞2 or＞3 years in terms of 1-year CR rate, hence is more cost-effective in clinical practice.

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EUS TA WITH FANNING TECHNIQUE OR CE-GUIDANCE ACHIEVE HIGH DIAGNOSTIC RATE FOR PANCREATIC CANCER Wan-Chih Yeh1, Wei-Yuan Chang1, Chieh-Chang Chen1, Yu-Ting Kuo2, Ming-Lun Han2, Chih-Hsiang Chen1, Hsuan-Ho Lin1, Po-Yen Jung1, Shih-Che Chen1, Ko-Han Chao1, Tsu-Yao Cheng3, Hsiu-Po Wang1 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan1 Department of Integrated Diagnostics Therapeutics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2 Department of laboratory medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan3

利用扇形採檢或超音波顯影劑導引之 內視鏡超音波細針穿刺有助於提高胰 臟惡性腫瘤診斷率 葉琬智1 張為淵1 陳介章1 郭雨庭2 韓明倫2 陳至翔1 林宣合1 戎伯岩1 陳世哲1 趙珂漢1 鄭祖耀3 王秀伯1 台大醫院內科部1 台大醫院綜合診療部2 台大醫院檢驗醫學部3 Background: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the current standard in diagnosis of pancreatic solitary lesions. To optimize tissue acquisition, several techniques or devices developed including suction method, fanning technique or new biopsy needles (FNB), etc. With the development of the contrast for ultrasound, contrast-enhanced EUS (CE-EUS) has high diagnostic accuracy in characterizing pancreatic adenocarcinoma. TA under conventional B mode after completing CEEUS observation or performing TA simultaneously under CE mode both improved diagnostic rate, compared with conventional EUS-TA. However, it is still unclear which TA technique mentioned above has better diagnostic rate in diagnosing pancreatic cancer.

Aims: To evaluate which TA technique influencing the EUS-TA diagnostic rate in pancreatic cancer.

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Methods: We searched our prospectively maintained EUS database for patients who underwent EUS-TA for suspected pancreatic cancer in National Taiwan University Hospital from January 2018 to May 2019. The patients were classified into three groups according to the TA method. In “Fanning group”, patients receiving conventional EUS-TA using Fanning technique.

In “CE-EUS assisted group”, TA was performed at conventional B node after contrast enhanced harmonic (CEH) EUS observation. For “CE-EUS guided group”, patients had simultaneous CEHEUS and CEH-EUS guided TA on CEH imaging.

We compared the diagnostic rate, first pass successful rate and complication rate among these three groups.

Results: A total of 191 patients were enrolled in this study. The most common diagnosis was adenocarcinomas (141, 73.8%), followed by neuroendocrine tumors (34, 17.8%). The overall diagnostic yield rate was 91.6% (175/191) and first passing positive rate was 84.6% (115/136).

There were no differences in major complications among these three groups. The diagnostic rate in Fanning group, CE-EUS assisted group and CE-EUS guided group were 97.1%, 84.88% and 97.22%, respectively (p＜0.01). The impact of CE-EUS guided and Fanning technique remain statistically significant after adjusting factors including using fine needle aspiration (FNA), FNB, suction method or rapid on-site evaluation (ROSE) (p=0.019).

Conclusions: In conclusion, the diagnostic rate was equal between conventional EUS-TA with fanning technique and CE-EUS guided TA. Performing TA under conventional B mode after completing CE-EUS observation will lead to a lower diagnostic yield rate.

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A RANDOMIZED TRIAL COMPARING THE EFFICACY OF SINGLE-DOSE AND DOUBLE-DOSE ADMINISTRATION OF RECTAL INDOMETHACIN IN PREVENTING POST-ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY PANCREATITIS Ching-Chung Lin1,2, Jian-Han Lai1,2, Chien-Yuan Hung1,2, Cheng-Hsin Chu1,2, Chih-Jen Chen1,2, Hsiang-Hung Lin1,2 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan1 Mackay Medical College, New Taipei City, Taiwan2

比較術後單次與術前及術後雙次 Indomethacin 塞劑來降低逆行性膽胰 管攝影術後併發胰臟炎的成效 林慶忠1,2 賴建翰1,2 洪建源1,2 朱正心1,2 陳志仁1,2 林相宏1,2 台北馬偕紀念醫院胃腸科1 馬偕醫學院2 Background: The before-procedure or afterprocedure rectal indomethacin administration was shown to be useful in preventing post-ERCP pancreatitis.

Aims: We designed this prospective randomized study to compare the efficacy of single-dose and double-dose rectal indomethacin administration in preventing PEP. Methods: We enrolled patients who underwent the ERCP in Taipei Mackay Memorial Hospital from 2016 Jun. to 2017 Nov. Patients were randomly assigned to two groups: single and double-dose groups. The primary endpoint was the frequency of post-ERCP pancreatitis.

Results: A total 162 patients participated in this study, and there were 87 patients randomly assigned to the single-dose group, and 75 patients were assigned to the double-dose group. In the high-risk patients, the incidence of PEP was lower in double-dose patients (4.8%)

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than the single-dose patients (9.5%), but there was no significant difference (p=0.24). Difficult cannulation was the only one risk factor for PEP after rectal indomethacin treatment.

Conclusions: Single-dose rectal indomethacin administration immediately after ERCP in general population is good enough to prevent PEP, but difficult cannulation could induce the PEP frequency up to 15.4% even under rectal indomethacin use.

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THE COMPARISON OF ENDOSCOPIC ULTRASOUNDGUIDED ANTEGRADE PANCREATIC STENTING AND RENDEZVOUS TECHNIQUE FOR FAILED ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY Ryosuke Tonozuka, Atsushi Sofuni, Takayoshi Tsuchiya, Kentaro Ishii, Reina Tanaka, Yukitoshi Matsunami Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan Background: Endoscopic ultrasound (EUS)guided pancreatic duct drainage (EUSPD) including EUS-guided antegrade stenting (EUSAG) and rendezvous technique (EUSRV) is a salvage method for failed endoscopic retrograde cholangiopancreatography (ERCP).

Data regarding a comparison between those two methods is rare.

Aims: To compare with outcomes of EUSAG. Methods: The medical records of 56 patients who underwent EUSPD (32 EUSAG and 24 EUSRV) for recurrent acute pancreatitis or abdominal pain due to main pancreatic duct stricture or stenotic pancreatojejunostomy from February 2010 to April 2019 at our institution.

R e s u l t s : Te c h n i c a l s u c c e s s r a t e w a s comparable between Group A than B (90.6 vs 70.8%, P=0.118). Median procedure time was significantly shorter in Group A than B (28.0 vs 57.0 min, P < 0.001). Regarding the rates of total adverse events (32.4 vs 60.0%, P=0.666), pancreatitis (5.4 vs 6.7%, P=0.631) and bleeding (2.7 vs 6.7%, P=0.902), there were significant difference between Group A and B. However, the post-procedure serum amylase level (143.0 vs 513.0 mg/dl, P=0.001) and the incidence of hyperamylasemia (18.9 vs 60.0%, P=0.003 ) were lower in Group A than B. Especially, in patients with surgically altered anatomy, hyperamylasemia was higher in Group B than A with a significant difference (20.7 vs 80.0%, P=0.031).

Conclusions: EUSAG was as safe as EUSRV,

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but EUS-RV tended to occur post-procedural hyperamylasemia. Considering procedure time and incidence of hyperamylasemia, EUSAG is suitable for failed ERCP cases with surgically altered anatomy. Besides, when EUSRV is performed even for a normal anatomy case, the procedure might be performed in two sessions.

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ANTIREFLUX METAL STENT VS. CONVENTIONAL COVERED METAL STENT FOR NONRESECTABLE DISTAL MALIGNANT BILIARY OBSTRUCTION: A RANDOMIZED CLINICAL TRIAL AND A POST HOC ANALYSIS Tsuyoshi Hamada1, Yousuke Nakai1, Tomotaka Saito1,2, Takuji Iwashita3, Yukiko Ito4, Osamu Togawa5, Hiroshi Yagioka6, Shomei Ryozawa7, Kenji Hirano8, T suyoshi Mukai9, Natsuyo Yamamoto10, Ichiro Yasuda11, Hiroyuki Isayama1,12, Kazuhiko Koike1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan1 Department of Gastroenterology, JR Tokyo General Hospital, Tokyo, Japan2 First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan3 Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan4 Department of Gastroenterology, Kanto Central Hospital, Tokyo, Japan5 Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan6 Department of Gastroenterology, Saitama Medical University International Medical Center, Saitama, Japan7 Department of Gastroenterology, JCHO Tokyo Takanawa Hospital, Tokyo, Japan8 Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan9 Department of Gastroenterology, Toshiba General Hospital, Tokyo, Japan10 Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, Kanagawa, Japan11 Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan12 Background: In patients with nonresectable distal malignant biliary obstruction, an antireflux metal stent (ARMS) may prevent recurrent biliary obstruction (RBO) due to the duodenobiliary reflux and thereby prolong time to RBO (TRBO).

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Aims: We aimed to evaluate the superiority of a newly-designed ARMS over conventional covered self-expandable metal stents (SEMSs).

Methods: We conducted a multicenter randomized controlled trial to test the hypothesis that an ARMS with a funnel-shaped valve might provide longer TRBO compared to a covered SEMS for patients without a history of SEMS placement. As secondary outcomes, we evaluated causes of RBO, adverse events, and patient survival. We evaluated effect modifications for the association of stent type with TRBO by clinical characteristics including duodenal tumor involvement.

Results: We enrolled 104 patients (52 patients per arm) between September 2014 and June 2016 at 11 hospitals in Japan. The median times to RBO were 251 and 351 days in the ARMS and covered SEMS groups, respectively (P=0.11).

RBO due to biliary sludge or food impaction was observed in 13% and 9.8% patients who received an ARMS and covered SEMS, respectively (P=0.083). The ARMS appeared to be at higher risk of migration compared to the covered SEMS (31% vs. 12%, respectively; P=0.038).

No significant between-group difference was observed for adverse events or patient survival.

We observed no statistically significant interaction of stent type with duodenal tumor involvement in relation to TRBO. Conclusions: The current trial failed to demonstrate the efficacy of the current antireflux valve in patients with distal malignant biliary obstruction. Further modifications including improvement of the anti-migration property are warranted to justify the use of the current ARMS as a first-line palliative treatment modality in this setting.

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RECURRENT OF CHOLEDOCHOLITHIASIS AFTER BILIARY INTERVENTIONS IN SINGLE MEDICAL CENTER EXPERIENCE FROM TAIWAN (20152018) Shih-Yuan Chen, Ta-Wei Wang, Chih-Sheng Hung, Ting-Chun Huang, Hsin-Yu Chen Division of Digestive medicine, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan

膽道介入性治療後患者膽管結石復發 率分析 陳世源 王大維 洪志聖 黃鼎鈞 陳信佑 國泰醫療財團法人國泰綜合醫院胃腸內科 Background: Recurrence of choledocholithiasis is usually happened after removal of stones by biliary interventions such as endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) or cholecystectomy with surgically or combined it. What determined the effect of recurrence of stones formation were not so unsure. We also not clear about recurrence after biliary interventions.

Aims: To determine the recurrence rate of ERCP with EST alone (group 1) or previous history of cholecystectomy more than 2 years and then ERCP with EST (group 2) or ERCP with EST followed by cholecystectomy within one month (group 3).

M e t h o d s : We c o l l e c t e d t h e E R C P d a t a in our single medical center for the period between January 2015 and December 2018 retrospectively. Data involved such as age, sex, body mass index and past history of hypertension, diabetes mellitus, dyslipidemia, and also included ERCP findings such as number of common bile duct (CBD) stones, CBD angle, CBD stricture, juxta-papillary diverticulum, duodenal ulcers.

Recurrence of symptomatic CBD stones is defined as detection of bile duct stones no sooner than six months after biliary interventions by clinically or radiological findings such as abdominal sonography, computed tomography, etc. We had separated three group of biliary interventions and closely monitoring the patients

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Section：Cirrhosis & HCC for about six months up to end of June 2019 whether recurrence choledocholithiasis or not.

We determined their recurrence rate using paired T test, chi squared test, relative risk, odd ratio.

Statistical analysis was performed using SPSS 22 for windows. Statistical significance was defined as a two tailed p value less than 0.05.

Results: At first, total 418 patients are collected in our ERCP data retrospectively. We exclude the patients who are not concerning about CBD stones, such as cancer patients, other causes of CBD obstructions, etc. and our study analyzed 365 patients with median age of 63.28(+/-15.58) and male to female ratio is 1.16:1 and BMI 24.94 (+/- 4.22). About 14.8% (54 patients) occurred recurrence and about 85.4 % (311 patients) found non-recurrence in our study patients, regardless of any biliary interventions. The analysis showed that past history of diabetes mellitus (OR=2.57, p=0.01), hypertension (OR=1.94, p=0.037), dyslipidemia (OR=1.33, p=0.077) and number of CBD stones (OR=0.67, p=0.008), CBD stricture (OR=2.98, p=0.001), juxta-papillary diverticulum (OR=1.36, p=0.075), duodenal ulcers (OR=1.048, p=0.299), CBD angle less than 135 (OR=1.33, p=0.077) were independent risk factors for recurrence of choledocholithiasis after biliary interventions. Three group of biliary interventions are reviewed, we observed in total 365 patients, group 1 had 30.9% (113 patients) which recurrence rate is 10.6% (12 patients) and non-recurrent rate is 89.4% (101 patients) : in group 2 had 24.9% (91 patients) which recurrent rate is 31.9% (29 patients) and non-recurrent rate is 68.1% (62 patients) : in group 3 had 44% (161 patients) which recurrent rate is 8.1% (13 patients) and non-recurrent rate is 91.9% (148 patients) but these are not statistically significant differences between these groups.

Conclusions: ERCP with EST followed by cholecystectomy (group 3) decrease recurrence of choledocholithiasis compared with ERCP with EST alone (group 1) or previous history of cholecystectomy and then ERCP with EST (group 2). Previous history of cholecystectomy more than two years, now biliary intervention with ERCP with EST have recurrent rate of choledocholithiasis within six months up to 30.9 percentage in our study, compared with other two groups. In conclusion, we should be closely monitoring in these patients for high risk of recurrence. We might be expected further clinical trial.

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BCLC-B SUBCLASSIFICATIONS ASSOCIATE WITH TUMOR RESPONSE AND LIVER DECOMPENSATION TO TRANSARTERIAL CHEMOEMBOLIZATION IN PATIENTS WITH HEPATOCELLULAR CARCINOMA Chen-Ta Chi1, I-Cheng Lee1, Rheun-Chuan Lee2, Chien-Wei Su1, Ming-Chih Hou1, Yee Chao3, Yi-Hsiang Huang1,4 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan2 Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan4

接受肝動脈化學栓塞治療之肝癌病患 其 BCLC B 次分期與腫瘤治療反應及 肝功能代償不全相關 齊振達1 李懿宬1 李潤川2 蘇建維1 侯明志1 趙毅3 黃怡翔1,4 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院放射線部2 臺北榮民總醫院癌症中心3 國立陽明大學臨床醫學研究所4 Background: Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). But heterogeneity in tumor and clinical characters result in varied responses to TACE. Aims: The study aimed to assess BCLC-B subclassifications in relating to liver decompensation and tumor response in patients treated with TACE. Methods: From October 2007 to January 2017, consecutive 531 BCLC-B HCC patients undergoing TACE in Taipei Veterans General Hospital were retrospectively reviewed. Objective response rate (ORR) was evaluated by RECIST

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1.1 and the incidence of liver decompensation among BCLC-B subclassifications (Bolondi’s, Kinki, and up-to-11 criteria) were evaluated.

Factors association with ORR and liver decompensation were analyzed.

Results: The ORRs were 51.2%, 38.5%, 16.7%, and 23.5% in Bolondi’s subclassification B1, B2, B3, and B4, respectively (p＜0.001); 50.6%, 36.9%, and 23.5% in Kinki criteria B1, B2, and B3, respectively (p=0.005); 50.2%, 26.6%, and 13.6% in “Up-to-11” subclassification B1, B2, and B3, respectively (p＜0.001). Age, AST, AFP, and the three BCLC subclassifications were factors associated with ORR. The incidences of liver decompensation in acute stage were 18.3%, 19.7%, 52.8%, and 76.5% in Bolondi’s B1, B2, B3, and B4, respectively (p＜0.001); 20.5%, 22.1%, and 76.5% in Kinki criteria B1, B2, and B3, respectively (p＜0.001); 16.6%, 32.6%, and 45.5% in “Up-to-11” subclassification B1, B2, and B3, respectively (p＜0.001). ALT＞40 IU/ L, AST＞45 IU/L, ALBI II/III, the three BCLC subclassifications, unilobar location, and AFP＞ 200 ng/mL were predictors of post-TACE liver decompensation. In addition, the incidence of chronic liver decompensation and ALBI grade migration were also associated with BCLC-B subclassification.

Conclusions: Not all BCLC B patients are eligible for TACE. The net benefit of TACE should be judged according to BCLC B subclassifications.

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SERUM PIVKAII LEVEL AT VIROLOGICAL REMISSION PREDICTS HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B RELATED CIRRHOSIS Shan-Han Chang1, Tung-Hung Su1,2, Cheng-Yuan Peng3,4, Tai-Chung Tseng1,2, Hung-Chih Yang1, Chun-Jen Liu1,2, Jia-Horng Kao1,2,5,6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan4 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan5 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan6

達病毒學緩解之慢性 B 型肝炎相關性 肝硬化之病人其血清 PIVKAII 數值可 預測肝細胞癌之發生 張善涵1 蘇東弘1,2 彭成元3,4 曾岱宗1,2 楊宏志1 劉俊人1,2 高嘉宏1,2,5,6 國立台灣大學醫學院附設醫院內科部胃腸肝膽科1 國立台灣大學醫學院附設醫院肝炎研究中心2 中國醫藥大學醫學院3 中國醫藥大學附設醫院內科部肝膽胃腸科4 國立台灣大學醫學院臨床醫學研究所5 國立台灣大學醫學院附設醫院醫學研究部6 Background: Serum PIVKAII is a diagnostic marker for hepatocellular carcinoma, and was approved in the latest Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma conducted by the Japan Society of Hepatology.

Aims: We aimed to investigate serum PIVKAII levels in predicting hepatocellular carcinoma (HCC) and all-cause mortality at virological remission (VR, HBV DNA＜20 IU/mL) following antiviral therapy in chronic hepatitis B (CHB)

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patients with cirrhosis.

Methods: This retrospective cohort study included patients with CHB-related cirrhosis undergoing long-term antiviral therapy from two tertiary medical centers in Taiwan. Serum PIVKAII levels at VR were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify the risk predictors for HCC and death. Serial on-treatment PIVKAII levels after VR were investigated.

Results: A total of 303 patients with CHB-related cirrhosis were included in the study. At time of VR, the median age was 55 (32-82) years, and the median PIVKAII level was 25 (5-4869) mAU/ mL. There were 62 patients developed HCC and 21 deaths during a median 52 (6-117) months of follow-up. After adjustment for age, sex, and alpha-fetoprotein levels, a higher PIVKAII level at VR significantly predicted HCC development (hazard ratio [HR]: 1.002, 95% confidence interval [CI]: 1.0004-1.004) but not death. In subgroup of 287 patients with AFP level＜20ng/mL, a higher PIVKAII level at VR significantly predicted HCC development (hazard ratio [HR]: 1.002, 95% confidence interval [CI]: 1.0003-1.004). Serial PIVKAII levels after VR increased in patients who developed HCC afterwards.

Conclusions: Serum PIVKAII levels at the time of antiviral therapy-induced VR predict HCC development in patients with CHB-related cirrhosis.

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REAL-WORLD EXPERIENCE OF NIVOLUMAB THERAPY FOR ADVANCED HEPATOCELLULAR CARCINOMA IN TAIWAN: EARLY REDUCTION OF SERUM ALPHAFETOPROTEIN ASSOCIATED WITH THERAPEUTIC RESPONSE AND OVERALL SURVIVAL Chen-Chun Lin1,3, Ming-Mo Ho2,3, Wei Teng1,3, Shi-Ming Lin1,3, Sheng-Fu Wang1,3, Chao-Wei Hsu1,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Department of Medical Oncology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Chang Gung University, Taoyuan, Taiwan3

免疫治療對晚期肝癌在臺灣的現實世 界經驗：早期下降血清中胎兒蛋白量與 治療反應及總存活有關 林成俊1,3 侯名模2,3 滕威1,3 林錫銘1,3 王昇富1,3 許朝偉1,3 林口長庚醫學中心胃腸肝膽科1 林口長庚醫學中心腫瘤科2 長庚大學3 Background: Nivolumab, an anti-PD1 inhibitors, was recently reported to have a moderate overall response with a durable response period for advanced hepatocellular carcinoma (HCC) in the Checkmate-040 clinical trial. But the real-world experience has not been reported.

Aims: To study the clinical results of nivolumab for advanced HCC patients in the real-world practice and to investigate the correlations between the early response of serum AFP and clinical outcomes.

Methods: We retrospectively reviewed the 108 patients who had advanced HCC and experienced nivolumab between August 2015 and December 2018 in our hospital. Six patients were excluded due to Child-Pugh class C. A total of 102 patient were enrolled with age (60.6±11.2 years old), Male gender (77.5%), Child-Pugh A/ B (82.3% /16.7%), HBV (66.7%), HCV (23.5%), EHS (63.7%), MVI (53.9%), BCLC stage B/C

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(12.8%/87.3%), and alpha-fetoprotein (AFP)＞ 20 ng/ml (74.5%) before nivolumab treatment.

Forty-two (41.2%) patients had no any systemic treatment experience. Sixty-nine (67.6%) patients received nivolumab 3 mg/kg as the starting dose and the median number of nivolumab treatment was 5 (1-67 cycles). Early AFP response was defined for baseline level＞20 ng/ml and reduced more than 20% as compared with baseline within the first 3 months after starting nivolumab. Image response was reviewed by an independent radiologist according to RECISTv1.1.

Results: Twenty-nine patients were still ongoing nivolumab treatment in the last follow-up. Of the 102 patients, CR, PR, SD, PD and no image evaluation were respectively found in 3 (2.9%), 15 (14.7%), 31 (30.4%), 29 (28.4%), and 24 (23.5%) patients. The objective response rate was 17.6% and disease control rate was 48.0%.

TTP and PFS were 3.0±0.4 and 4.2±1.2 months, respectively. The median duration of the responders was 19.4 months. The median OS was 11.4±3.0 months. Early AFP response was found in 35 (34.3%) patients. The early AFP responders had a significantly higher image response rate (40.0% vs 6.0%, P＜0.001) and had a better overall survival (median: not reach vs 8.3 months, P=0.006) as compared to the early AFP non-responders. Early AFP response was independently associated with therapeutic image response (P＜0.001, OR=9.294, 95% CI=2.68532.167) and better overall survival (P=0.001, HR=0.292, 95% CI=0.141-0.604).

Conclusions: Nivolumab therapy for advanced HCC in the real-world of HBV-predominant Chinese patient were similar to the clinical trial, despite of their more advanced condition.

Early AFP response is associated with a higher therapeutic response and a better overall survival.

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THE THERAPEUTIC BENEFIT OF COMBINATION OF SORAFENIB AND TRANSARTERIAL CHEMOEMBOLIZATION FOR BCLC STAGE C HEPATOCELLULAR CARCINOMA Shou-Wu Lee1,2, Teng-Yu Lee1,2, Sheng-Shun Yang1,3, Chun-Fang Tung1, Hong-Zen Yeh1,3, Chi-Sen Chang1,2 Division of Gastroenterologyand Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan1 Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan2 Department of Internal Medicine, Yang-Ming University, Taipei, Taiwan3

合併蕾莎瓦與經動脈導管肝臟腫瘤化 學栓塞術對於 BCLC Stage C 肝細胞 腫瘤患者之治療效益分析 李少武1,2 李騰裕1,2 楊勝舜1,3 童春芳1 葉宏仁1,3 張繼森1,2 臺中榮民總醫院胃腸肝膽科1 中山醫學大學醫學系2 陽明大學醫學系3 Background: Hepatocellular carcinoma (HCC) is the commonest primary liver cancer worldwide.

The BCLC staging system is widely used for selecting its treatment, and stage C is typically treated with sorafenib. However, the survival benefit observed after sorafenib treatment is limited.

Aims: The aim of the present study is to determine the outcomes of the patients with BCLC stage C HCC that accept combined sorafenib and TACE therapy.

Methods: Data for subjects with HCC, BCLC stage C, who were receiving sorafenib at VGHTC from August 2012 to September 2017 was evaluated. The exclusion criteria included those cases diagnosed with cirrhosis Child-Pugh stage B or C, HCC BCLC stage A or B, or lack of compliance to drugs. These patients accepted TACE for viable HCC or not, which determined by an experienced hepatologist. The subjects accepted sorafenib alone were classified as the monotherapy group, and the ones accepted

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sorafenib and TACE were classified as the combined therapy group.

Results: A total of 118 subjects, 65 belonged to the monotherapy group and 53 belonged to the combined therapy group, were enrolled. The age, gender distribution, HCC size, number, presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS), were similar. The outcomes involving (TTP) and (OS) are shown in Table 1 and Figure 1. The subjects of the combined therapy group displayed a significantly TTP (mean 6.42 vs. 3.63 months, p=0.003) and OS (mean 11.21 vs. 5.98 months, p=0.001) than those of the monotherapy. To the enrolled patients with MVI, the subjects in the combined therapy group had a significantly longer TTP (mean 7.93 vs. 3.43 months, p=0.007) and OS (mean 9.20 vs. 4.37 months, p=0.001) than those with MVI. However, to the those with EHS, these significant differences did not exist.

Conclusions: The combination of TACE and sorafenib brings a significant better outcome, than sorafenib alone, for the patients with BCLC stage C HCC along with MVI.

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A MODEL TO PREDICT SURVIVAL AFTER TRANSARTERIAL CHEMOEMBOLIZATION FOR PATIENTS WITH SOLITARY HEPATOCELLULAR CARCINOMA LARGER THAN 5 CM Kebin Chang1, I-Cheng Lee1,2, Chen-Ta Chi1, Rheun-Chuan Lee3, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2,4 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan2 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan4

在單一大於五公分肝細胞癌接受經動 脈化學栓塞後存活預測模組研究 張可斌1 李懿宬1,2 齊振達1 李潤川3 侯明志1,2 黃怡翔1,2,4 臺北榮民總醫院胃腸肝膽科1 陽明大學陽醫學系2 臺北榮民總醫院放射部3 陽明大學臨床醫學研究所4 Background: For patients with solitary hepatocellular carcinoma (HCC) larger than 5 cm not suitable for surgical resection, transarterial chemoembolization (TACE) is an alternative treatment. However, the response rate and survival predictors after TACE remain unclear.

Aims: This study aimed to evaluate the treatment response and survival in this population.

Methods: Consecutive 161 treatment-naïve patients with solitary HCC larger than 5 cm undergoing TACE as the initial treatment were retrospective enrolled. Radiologic response after first TACE was evaluated by modified RECIST criteria. Factors associated with overall survival (OS) were analyzed.

Results: Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 8.7%, 24.8%, 32.9% and 36% of patients, respectively.

The median OS in patients with CR, PR, SD

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Section：UGI and PD were 71.4, 44.8, 17.7 and 14.3 months, respectively. By multivariate analysis, ALBI grade 2 or 3 (hazard ratio (HR)=2.184, p=0.001), tumor size＞7 cm (HR=1.960, p=0.005), serum creatinine＞1.2 mg/dL (HR=1.691, p=0.030) and achieving complete or partial response (HR=0.508, p=0.003) were independent predictors of OS. Tumor size was the only independent factor associated with radiologic response after initial TACE (odds ratio=0.867 per 1 cm increase, p=0.014). A prognostic model was developed to classify patients into low, intermediate and high risk of mortality (median OS of 75.8, 35.1 and 12.9 months, respectively, p＜0.001).

Conclusions: ALBI grade, tumor size, renal function and radiologic response are important predictors of survival in patients with solitary HCC larger than 5 cm undergoing TACE. A prognostic model can be applied to discriminate patient’s survival after TACE.

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LEVOFLOXACIN SEQUENTIAL THERAPY VERSUS BISMUTH QUADRUPLE THERAPY IN THE SECOND-LINE AND THIRD-LINE TREATMENT OF HELICOBACTER PYLORI – A MULTICENTER RANDOMIZED TRIAL Jyh-Ming Liou1, Yu-Jen Fang2, Po-Yueh Chen3, Chieh-Chang Chen1, Ming-Jong Bair4, Ming-Shiang Wu1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan2 Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan3 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taitung Branch, Taitung, Taiwan and Mackay Medical College, New Taipei City, Taiwan4

比較含可樂必妥的系列性四合一治療 與含鉍劑四合一治療在幽門螺旋桿菌 感染第二線及第三線的治療—一項多 中心隨機分派比較試驗 劉志銘1 方佑仁2 陳柏岳3 陳介章1 白明忠4 吳明賢1 臺大醫院內科1 臺大醫院雲林分院內科2 嘉義基督教醫院3 台東馬偕紀念醫院4 Background: The efficacy of levofloxacinbased triple therapy is lower than 80% in the second-line treatment of Helicobacter pylori (H. pylori) infection. Our recent trial showed that levofloxacin-based sequential therapy was superior to levofloxacin-based triple therapy in the second-line treatment of H. pylori.

Aims: We aimed to compare the efficacy and safety of 14-day levofloxacin sequential therapy versus 10-day bismuth quadruple therapy in the second-line and third-line treatment of H. pylori infection.

Methods: H. pylori infected patients who failed after one treatment were eligible in this open labeled, multicenter, randomized trial, and were

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randomized to receive (1) levofloxacin sequential therapy (EAML): esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily); or (2) bismuth quadruple therapy (BQ): esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days. The primary end point was the eradication rate in the second-line treatment according to intention to treat (ITT) analysis. The minimum inhibitory concentrations were determined by agar dilution test.

Results: A total of 560 patients have been recruited and results were available for analysis in 533 patients up to Jan 2019. The demographic characteristics and antibiotic resistance rates were similar across the two treatment groups.

The eradication rate in the second line treatment were 88.3% (235/266) and 88.4% (236/267) in the levofloxacin sequential therapy and bismuth quadruple therapy groups, respectively (p=1.000) in the ITT analysis. The eradication rates were 89.7% (235/262) and 92.9% (236/254) in the levofloxacin sequential therapy and bismuth quadruple therapy according to PP analyses, respectively (p=0.195). The efficacy of levofloxacin sequential therapy, but not bismuth quadruple therapy, appeared to be affected by levofloxacin resistance. The frequency of any adverse effects was higher in patients treated with bismuth quadruple therapy than levofloxacin sequential therapy (76.4% vs. 44.1%, p＜0.001).

Conclusions: Levofloxacin sequential therapy and bismuth quadruple therapy are similarly effective in the second-line treatment for H. pylori infection (Trial registration number: NCT NCT03148366).

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PROBIOTICS-CONTAINING YOGURT INGESTION AND H. PYLORI ERADICATION CAN RESTORE FECAL FAECALIBACTERIUM PRAUSNITZII DYSBIOSIS IN H. PYLORIINFECTED CHILDREN Yao-Jong Yang1,2, Peng-Chieh Chen2, Fu-Ping Lai1, Bor-Shyang Sheu2,3 Departments of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan1 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan2 Departments of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan3

飲用含益生菌優酪乳與除菌可改善幽 門桿菌感染孩童後糞便中柔嫩梭菌數 量之減少 楊燿榮1,2 陳芃潔2 賴馥蘋1 許博翔2,3 國立成功大學醫學院附設醫院小兒部1 國立成功大學醫學院臨床醫學研究所2 國立成功大學醫學院附設醫院內科部3 Background: H. pylori infection can alter the diversity and richness of gut microbiota, and probiotics ingestion can improve H. pylori-induced gastric and systemic inflammation in vivo and in vitro.

A i m s : To i n v e s t i g a t e t h e c o m p o s i t i o n a l differences in fecal microbiota between children with and without H. pylori infection, and to test whether probiotics-containing yogurt and H. pylori eradication can improve dysbiosis in children.

Methods: Ten H. pylori-infected children and 10 age- and sex-matched controls were enrolled to ingest probiotics-containing yogurt for 4 weeks. Ten-day triple therapy plus yogurt was given to the H. pylori-infected children on the 4th week. Fecal samples were collected at enrollment, after yogurt ingestion, and 4 weeks after successful H. pylori eradication. Fecal secretory immunoglobulin A and cytokines were measured by ELISA. The composition of fecal microbiota was checked through metagenomic sequencing of the V4 region of the 16S rRNA

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gene. The OTUs demonstrating major changes in relative abundance were identified by LEfSe and Metastats.

Results: On average, 1.6 M reads were obtained for each of the 37 fecal samples. The sequences were aligned and clustered into 295 OTUs. The H. pylori-infected children had higher levels of transforming growth factor-beta1 in the fecal samples than those who were not infected (P=0.02). We identified eight significantly altered OTUs in the H. pylori-infected children. Among them, the abundance of Faecalibacterium prausnitzii was significantly lower in the H. pylori-infected children and then increased after yogurt ingestion and successful eradication of H. pylori (P＜0.05). Pretreatment with F. prausnitzii supernatant significantly ameliorated lipopolysaccharide-induced IL-8 in HT-29 cells.

Conclusions: Probiotics-containing yogurt ingestion and H. pylori eradication can restore the decrease of fecal F. prausnitzii in H. pyloriinfected children.

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RISK FACTORS OF MUCOSAL BREAK IN LOW-DOSE ASPIRIN USERS WITH SECOND PREVENTION OF GASTROINTESTINAL INJURY BY ACID INHIBITORS Zhi-Fu Tseng1,2, Sung-Shuo Kao1, Feng-Woei Tsay1, Jin-Shiung Cheng1, Wen-Chi Chen1, Ping-I Hsu1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 Diagnostic and Therapeutic Endoscopy Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan2

使用抑酸劑作胃腸傷害之次級預防的 阿斯匹靈使用者發生胃腸黏膜破損的 危險因子 曾稚富1,2 高崧碩1 蔡峯偉1 鄭錦翔1 陳文誌1 許秉毅1,2 高雄榮民總醫院胃腸肝膽科1 高雄榮民總醫院內視鏡診斷暨治療中心2 Background: Low-dose aspirin (75-325 mg/day) is widely used in the prevention of myocardial infarction or ischemic stroke. However, use of aspirin is associated with an increased risk of gastrointestinal injury including erosion, ulcer and ulcer bleeding.

A i m s : To i n v e s t i g a t e t h e r i s k f a c t o r s o f gastroduodenal mucosal break in low-dose aspirin users with second prevention of gastrointestinal injury by acid inhibitors.

Methods: Long-termed low-dose aspirin users with atherosclerotic diseases and peptic ulcer history who did not have peptic ulcers or erosions at initial endoscopy were randomly assigned to receive either famotidine (20 mg bid) or omeprazole (20 mg qd) for 24 weeks. Follow-up endoscopy was conducted at the end of week 24 and whenever bothersome dyspeptic symptoms, hematemesis or tarry stool developed. The major outcome measure was gastroduodenal mucosal break (erosion/ulcer). Multivariate analysis was conducted to search the risk factors of mucosal breaks.

Results: From Nov 2013 to June 2018, 250

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patients were randomly to receive either famotidine (n=122) or omeprazole (n=128).

The incidence of gastroduodenal mucosal break during the 24-week period was 32.1% in famotidine group and 18.6% in omeprazole group.

The latter had a lower incidence of mucosal break than the former (95% confidence interval: -24.25%—-2.8%). Univariate analysis revealed that omeprazole use was associated with a lower risk of mucosal break (P=0.042), and smoking was associated with an increased risk of mucosal break (55.6% vs 21.7%; P=0.013). Multivariate analysis showed that omeprazole use was an independent protective factor (odds rate: 0.46; 95% CI: 0.22—0.96; P=0.038), and smoking was a risk factor of mucosal break (odds rate: 3.03; 95% CI: 1.26—7.26; P=0.013) Conclusions: In low-dose aspirin users with second prevention of gastrointestinal injury by acid inhibitors, proton pump inhibitor is more effective than histamine-2 receptor antagonist.

Smoking is an independent risk factor of the development of mucosal break in patients with secondary prevention of gastrointestinal injury by low-dose aspirin.

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A CLINICAL PERFORMANCE STUDY COMPARING THE VSTRIP® HELICOBACTER PYLORI ANTIGEN RAPID TEST AND IMMUNOCARD STAT!® HPSA FOR THE DETECTION OF HELICOBACTER PYLORI IN STOOL SAMPLES COLLECTED FROM PATIENTS WITH UPPER GASTROINTESTINAL COMPLAINTS OR VOLUNTEERS FROM THE GENERAL POPULATION Yu-Jen Fang1, Chieh-Chang Chen1,2, Ji-Yuh Lee1, Ming-Shiang Wu2, Jiing-Chyuan Luo3, Jyh-Ming Liou2 Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, College of Medicine, National Taiwan University Yunlin, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Department of Medicine, National Yang-Ming University, School of Medicine and Taipei Veterans General Hospital, Taipei, Taiwan3

比較 Vstrip® Helicobacter Pylori Antigen Rapid Test 和 ImmunoCard STAT!® HpSA 兩者幽門螺桿菌糞便抗 原檢測之準確性 方佑仁1 陳介章1,2 李基裕1 吳明賢2 羅景全3 劉志銘2 國立臺灣大學醫學院附設醫院雲林分院內科1 國立臺灣大學醫學院附設醫院內科2 國立陽明大學醫學系暨臺北榮民總醫院內科3 Background: Vstrip ® Helicobacter pylori Antigen Rapid which is an in-vitro diagnostic medical devise (IVDD) to perform rapid immunochromatographic assay that can quickly detect H. pylori antigens in stool samples to ascertain the presence of H. pylori infection.

Aims: This open-label, cross-sectional, multiplecenter clinical performance study aimed to compare the Vstrip® H. pylori Antigen Rapid Test with the US FDA-approved ImmunoCard STAT!® HpSA test for substantial equivalence in detecting H. pylori in stool samples, as based on validated

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detection results derived via the urea breath test (UBT).

Methods: A total of 352 adult subjects were recruited. Stool samples were collected for Vstrip® H. pylori Antigen Rapid Test, ImmunoCard STAT!® HpSA test and Premier Platinum HpSA® PLUS. 13C-Urea Breath Test (13C-UBT) was used as the gold standard test. All subjects who have completed the stool sample collections were included in the ITT analysis. The sensitivity, specificity, and positive and negative likelihood ratios for the investigational devices were determined with reference to the results of the UBT validation.

Results: The prevalence of H. pylori infection was 22.4% (79/352, 95% CI 18.3-27%) in this study population. The sensitivity of the Vstrip® HpSA and ImmunoCard STAT!® HpSA tests were 91% (72/79, 95% CI 82-96%) and 77.2% (61/79, 95% CI 66-86%), respectively. The specificity of the Vstrip® HpSA and ImmunoCard STAT!® HpSA tests were 97% (265/273, 95% CI 94.198.6%) and 97% (265/273, 95% CI 94.1-98.6%), respectively. The accuracy of the Vstrip® HpSA and ImmunoCard STAT!® HpSA tests were 95% (335/352, 95% CI 92-97%) and 92% (326/352, 95% CI 89-95%), respectively.

Conclusions: The Vstrip® HpSA has equivalent performance as the ImmunoCard STAT!® HpSA, and has the potential to become a self-testing in vitro diagnostic medical device.

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MATERNAL HELICOBACTER PYLORI-SEROPOSITIVE IS ASSOCIATED WITH GESTATIONAL HYPERTENSION BUT IRRELEVANT TO GROWTH AND DEVELOPMENT OF EARLY CHILDHOOD Shu-Han Kuo1, Fu-Ping Lai1, Yi-Fang Tu1,2, Bor-Shyang Sheu1,3, Yao-Jong Yang1,2 Departments of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan1 Departments of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan2 Institutes of Clinical Medicine, National Cheng Kung University Hospital, Tainan, Taiwan3

母體幽門桿菌血清陽性與妊娠高血壓 相關但與幼兒生長發育無關 郭舒涵1 賴馥蘋1 杜伊芳1,2 許博翔1,3 楊燿榮1,2 成功大學醫學院附設醫院小兒部1 成功大學醫學院附設醫院內科部2 成功大學臨床醫學研究所3 Background: H. pylori infection during pregnancy is related to several adverse outcomes in both mothers and neonates. However, maternal H. pylori infection impacts on the growth and neurodevelopment potential of the fetus remained controversial.

Aims: The aim of this study was to explore the influences of maternal H. pylori infection on pregnancy-related adverse events, cord blood levels of growth-related hormones, fetal growth, and early childhood development.

Methods: The prospective cohort study recruited singleton pregnant women without major medical illnesses from January 2014 to January 2015.

Demographic data for the cohort and medical issues related to pregnancy were recorded. The seropositivity of H. pylori is defined as＞12 U/ ml of anti-H. pylori IgG in maternal serum. Cord blood levels of insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein-3 (IGFBP-3), insulin, and ghrelin were determined using ELISA. Eligible newborns were monitored for growth for up to 3 years each year, and the cognitive development was evaluated using the comprehensive developmental inventory for

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infants and toddlers (CDIIT) test at 3 years of age.

Results: Of the 106 enrolled women, 25 (23.6%) were H. pylori-seropositive. Maternal H. pylori seropositivity was associated with a higher risk of developing gestational hypertension (GH) (12% vs. 1.2%, p=0.04) and lower cord blood levels of IGF-1 (ďź&#x153;35 ng/ml, 70.0% vs. 40.7%, p=0.02) and IGFBP-3 (ďź&#x153;1120 ng/ml, 100.0% vs.

76.3%, p=0.02) compared with the seronegative women. No significant impact on birth weight, childhood growth and cognitive development was found to be associated with maternal H. pylori seropositivity during pregnancy.

Conclusions: Maternal H. pylori infection during pregnancy was more likely to develop gestational hypertension, but not correlated with the growth and development of fetus and childhood. In addition to close monitoring of hypertension, H. pylori eradication can be considered for such H. pylori-infected mothers.

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Poster Section：Liver P.001

A PHASE 3 STUDY COMPARING SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIR ALAFENAMIDE (TAF) WITH CONTINUED TDF TREATMENT IN VIROLOGICALLYSUPPRESSED PATIENTS WITH CHRONIC HEPATITIS B (CHB): WEEK 48 EFFICACY AND SAFETY RESULTS Wan-Long Chuang1, Pietro Lampertico2, Maria Buti3, Scott Fung4, Sang Hoon Ahn5, Won Young Tak6, Alnoor Ramji7, Chi-Yi Chen8, Edward Tam9, Ho Bae10, Xiaoli Ma11, John F Flaherty12, Anuj Gaggar12, Audrey Lau12, Becket Feierbach12, George Wu12, Vithika Suri12, G Mani Subramanian12, Huy Trinh13, Seung-Kew Yoon14, Kosh Agarwal15, Young-Suk Lim16, Henry LY Chan17 Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan1 Università Degli Studi di Milano, Italy2 Hospital Universitari Vall d'Hebron, Barcelona, Spain3 Toronto General Hospital, Toronto, Ontario, Canada4 Yonsei University, Severance Hospital, Seoul, South Korea5 Kyungpook National University Hospital, Daegu, South Korea6 GI Research Institute, Vancouver, British Columbia, Canada7 Chia-Yi Christian Hospital, Chia-Yi City, Taiwan8 LAIR Centre, Vancouver9 Asian Pacific Liver Center, Los Angeles, California, USA10 Hahnemann University Hospital, Philadelphia, Pennsylvania, USA11 Gilead Sciences, Inc., Foster City, California12 Silicon Valley Research Institute, San Jose, California13 The Catholic University of Korea, Seoul14 King’s College Hospital, London, UK15 Asan Medical Center, Seoul16 The Chinese University of Hong Kong, China17

Background: TAF, a novel prodrug of tenofovir (TFV), was recently approved for treatment of CHB. TAF has greater plasma stability, more targeted delivery of TFV to the liver, and reduced circulating levels of TFV compared to TDF at approved doses. TAF has shown efficacy noninferior to TDF with improved renal and bone safety in viremic CHB patients at Weeks 48 and 96.

Aims: We evaluated efficacy and safety in stable, virally-suppressed patients who were switched from TDF to TAF vs. continued TDF for an additional year.

Methods: In this Phase 3 study (NCT02979613), CHB patients on TDF for ≥ 48 weeks with HBV DNA＜LLOQ (local laboratory) for ≥ 12 weeks and＜20 IU/mL at screening were randomized (1:1) to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 48 weeks.

After this, all patients received open-label TAF for an additional 48 weeks. The primary efficacy analysis was the proportion of patients with HBV DNA ≥ 20 IU/mL at Week 48 based on the modified US FDA-defined Snapshot algorithm; the study was powered to show non-inferiority in efficacy of TAF compared to TDF, with a 4% margin. Key prespecified secondary safety endpoints were assessed sequentially: changes in hip and spine bone mineral density (BMD), and changes in estimated creatinine clearance

by Cockcroft-Gault (eGFRCG). Markers of bone turnover and renal tubular function were serially assessed. Viral resistance was evaluated by population sequencing those patients who experienced virologic breakthrough or viremia at the time of discontinuation.

Results: 488 patients were randomized and treated at 42 sites in 8 countries. At baseline the groups were similar: median age 52 y (22% ≥ 60y), 71% male, 82% Asian, 68% HBeAgnegative, and median ALT 23 U/L. Median eGFRCG was 90.5 mL/min; 45% and 50% had low BMD by T scores at hip and spine, respectively. Median (Q1, Q3) duration of prior TDF was 222 (145, 305) weeks. Key efficacy/ safety results are summarized in the Table. TAF demonstrated non-inferior efficacy to TDF with a similar rate (0.4%) having HBV DNA ≥ 20 IU/ mL at Week 48, (difference in proportions: 0.0%, 95% CI, -1.9% to +2.0%). TAF treatment resulted in increases in hip/spine BMD with less impact

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on bone turnover makers; switching from TDF to TAF also resulted in increased eGFRCG and decreases in markers of tubular function. Rates of ≥ Grade 2 adverse events (AEs) and serious AEs were low and similar between groups. No viral resistance was observed in the 3/243 (1.2%) and 2/245 (0.8%) TAF and TDF patients, respectively, who qualified for testing.

Conclusions: Virologically-suppressed CHB patients who were switched to TAF demonstrated noninferior efficacy to continued TDF with improved bone and renal safety.

P.002

ALGORITHMS USING NONINVASIVE TESTS CAN ACCURATELY IDENTIFY PATIENTS WITH ADVANCED FIBROSIS DUE TO NASH: DATA FROM THE STELLAR CLINICAL TRIALS Pin-Nan Cheng1, Zobair M. Younossi2, Eric J. Lawitz3, Naim Alkhouri3, Vincent Wai-Sun Wong4, Manuel Romero-Gomez5, Takeshi Okanoue6, Michael Trauner7, Kathryn Kersey8, Georgia Li8, G. Mani Subramanian8, Robert P. Myers8, C. Stephen Djedjos8, Ling Han8, Guang Chen8, Tuan Nguyen8, Anita Kohli9, Natalie Bzowej10, Ziad Younes11, Shiv Sarin12, Mitchell L. Shiffman13, Stephen A. Harrison14, Zachary Goodman2, Nezam H. Afdhal15, Maria Stepanova16, Quentin M. Anstee17 Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan1 Inova Fairfax Hospital, Falls Church, VA, USA2 Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA3 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong4 Hospital Universitario Virgen del Rocio, Sevilla, Spain5 Saiseikai Suita Hospital, Suita City, Osaka, Japan6 Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria7 Gilead Sciences, Inc., Foster City, CA, USA8 The Institute for Liver Health, Chandler, AZ, USA9 Ochsner Medical Center, New Orleans, LA, USA10 Gastro One, Germantown, TN, USA11 Institute of Liver and Biliary Sciences, New Delhi, Delhi, India12 Bon Secours Mercy Health, Liver Institute of Virginia, Richmond, Virginia, USA13 Pinnacle Clinical Research, San Antonio, TX, USA14 Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA15 CCenter for Outcomes Research in Liver

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Diseases, Washington DC, USA Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK17 16

Background: There is a major unmet need for accurate, readily available, noninvasive tests (NITs) to identify patients with advanced fibrosis (F3-F4) due to NASH. Aims: Our goal was to evaluate sequential NIT algorithms to minimize the requirement for biopsy and improve accuracy over use of single tests.

Methods: The STELLAR studies (NCT03053050, NCT03053063) enrolled NASH patients with bridging fibrosis (F3) or compensated cirrhosis (F4). Baseline liver biopsies were centrally read using the NASH CRN fibrosis classification and noninvasive fibrosis markers, including the Fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and FibroScan® (FS) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using AUROCs with 5-fold cross-validation repeated 100x. Thresholds were obtained by maximizing specificity given ≥85% sensitivity (and vice versa). The cohort was divided (80%/20%) into evaluation/validation sets. The evaluation set was further stratified 250x into training and test sets (66%/33%). Optimal thresholds were derived as the average across training sets, and applied sequentially (FIB-4 followed by ELF and/or FS) to the validation set.

Results: All patients with available liver histology (N=3202, 71% F3-F4) and NIT results were included. While single tests were able to discriminate advanced fibrosis, up to 32% of patients had an indeterminate result. Using thresholds derived from STELLAR data, FIB-4 followed by FS or ELF in those with indeterminate FIB-4 values (1.23 to 2.1) reduced indeterminate results to as low as 13% (Table). Misclassification occurred at rates similar to biopsy (15-21%).The majority of misclassifications (63-81%) were false negatives; among false positive cases (19-27% of misclassifications), up to 70% had F2 fibrosis.

Conclusions: In these large, global, phase 3 trials with newly derived thresholds optimized for the STELLAR trials, FIB-4 followed by ELF and/ or FS nearly eliminated the need for liver biopsy and accurately identified patients with advanced fibrosis due to NASH with misclassification rates similar to liver biopsy.

P.003

ROUTINELY AVAILABLE NONINVASIVE TESTS DISCRIMINATE ADVANCED FIBROSIS DUE TO NASH IN THE PHASE 3 STELLAR TRIALS OF SELONSERTIB Pin-Nan Cheng1, Q.M. Anstee2, E.J. Lawitz3, N Alkhouri3, V.W.S Wong4, M RomeroGomez5, T Okanoue6, M Trauner7, K Kersey8, G Li8, G.M Subramanian8, R.P. Myers8, C.S Djedjos8, L Han8, Y Li8, T Nguyen8, A Kohli9, N Bzowej10, Z Younes11, S Sarin12, M.L Shiffman13, S.A Harrison14, Z Goodman15, Z.M. Younossi15 Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan1 Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK2 Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA3 Department of Medicine and Therapeutics, The Chinese Hospital of Hong Kong, Hong Kong4 Hospital Universitario Virgen del Rocio, Sevilla, Spain5 Saiseikai Suita Hospital, Suita City, Osaka, Japan6 Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria7 Gilead Sciences, Inc., Foster City, CA, USA8 The Institute for Liver Health, Chandler, AZ, USA9 Ochsner Medical Center, New Orleans, LA, USA10 Gastro One, Germantown, TN, USA11 Institute of Liver and Biliary Sciences, New Delhi, Delhi, India12 Bon Secours Liver Institute of Virginia, Richmond, Virginia, USA13 Pinnacle Clinical Research, San Antonio, TX, USA14 Inova Fairfax Hospital, Falls Church, VA, USA15 Background: Liver biopsy is currently the reference standard for fibrosis staging, but is an invasive procedure with limitations. There is a major unmet need for accurate, readily available

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noninvasive tests (NITs) to identify patients with advanced fibrosis due to NASH. Aims: Our aim is to describe the performance of NITs using the baseline data from the Phase 3 STELLAR studies of the ASK1 inhibitor selonsertib (SEL).

Methods: The STELLAR studies (NCT03053050 and NCT03053063) enrolled patients with bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH (NAFLD Activity Score [NAS] ≥3). Baseline liver biopsies were centrally read according to the NASH CRN fibrosis classification and noninvasive markers of fibrosis, including the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness (LS) by transient elastography (TE; FibroScan®) were measured. The performance of these tests to discriminate advanced (F3F4) fibrosis was evaluated using AUROCs with 5-fold cross-validation repeated 100x. Optimal thresholds for F3-F4 fibrosis were selected based on the literature. Data presented are from an interim analysis on 26 July 2018.

Results: A total of 4030 patients were screened.

In the 3202 with evaluable histology (median age 58 years, 55% women, 71% Caucasian, 24% Asian, 60% with diabetes), median biopsy length was 2.0 cm, 8% F0, 9% F1, 13% F2, 31% F3, 40% F4, 59% with NAS ≥5. Median values of NFS, FIB-4, ELF, and LS by TE increased with worsening fibrosis (-0.972/1.18/9.22/8.8 kPa in F0-F2 vs 0.318/2.20/10.39/16.5 kPa in F3-F4, respectively). AUROCs ranged from 0.74 to 0.80 to discriminate advanced fibrosis (Table 1). When tests were combined, performance characteristics improved and PPVs ≥98% were possible.

Conclusions: In these large, global phase 3 trials of SEL, routinely available NITs demonstrated acceptable diagnostic performance for the discrimination of advanced fibrosis due to NASH.

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P.004

ROLES OF ANTIVIRAL AGENTS ON THE RATIO OF A1762T/ G1764A AND PROGRESSION OF LIVER FIBROSIS AFTER HBEAG SEROCONVERSION Jia-Feng Wu, Hong-Yuan Hsu, Mei-Hwei Chang Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

抗病毒藥對 B 型肝炎 e 抗原抗體血清 轉換後病毒 A1762T/G1764A 突變比 例及肝纖維化的影響 吳嘉峯 許宏遠 張美惠 台大醫院小兒部

Background: Liver fibrosis is an ominous late complication of chronic hepatitis B virus (HBV) infection, and mostly occurred after hepatitis B e antigen (HBeAg)-seroconversion.

Aims: We intent to elucidate the impact of antiviral therapy on the percentage of the HBV immune escape mutants from inflammatory phase to the accomplishment of HBeAg-seroconversion, and the progression of liver fibrosis in subjects with chronic HBV infection.

Methods: We enrolled 160 chronic HBV infected subjects followed in our institution since 8.28±0.59 years of age, and enter their inflammatory phase with the accomplishment of HBeAg-seroconversion into this study. We quantified the percentage of HBV mutant strains (A1762T/G1764A, G1896A, C2063A, A2131C, and C2304A HBV core gene mutants) in each subjects from the serum samples obtained at the inflammatory phase and after HBeAgseroconversion by pyrosequencing. The liver stiffness measurement (LSM) is assessed by transient elastography at 31.54±0.79 years of age (12.76±0.75 years after their HBeAgseroconversion). The relationship between antiviral agents, proportion of HBV mutants at difference phase, and the LSM were analyzed.

Results: The percentage of A1762T/G1764A, C2063A, and A2131C mutants in each subjects is significantly higher in the group with LSM＞7 kPa (METAVIR F2-4) than the group with LSM ≤ 7 kPa (METAVIR F0-F1) after HBeAg-seroconversion.

There is no statistic difference in the percentage

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of A1762T, G1764A, G1896A, C2063A, A2131C, and C2304A at the inflammatory phase before HBeAg-seroconversion between subjects with LSM＞7 kPa (METAVIR F2-F4) and LSM ≤ 7 kPa (METAVIR F0-F1). Subjects with interferon, entecavir and tenofovir therapy before HBeAgseroconversion had lower percentage of A1762T/G1764A after HBeAg-seroconversion as compared with spontaneous HBeAgseroconverters and those treated with lamivudine (P all＜0.05). The percentage of A1762T/G1764A after HBeAg-seroconversion is positive correlated with the LSM (P=0.002) in the study cohort.

Conclusions: The percentage of A1762T/ G1764A mutation after HBeAg-seroconversion is associated with liver fibrosis. Interferon, entecavir and tenofovir, but not lamivudine, may decrease the percentage of A1762T/G1764A mutation after HBeAg-seroconversion and the occurrence of liver fibrosis.

P.005

IMPROVEMENT IN VIROLOGIC, BIOCHEMICAL AND RENAL OUTCOMES IN CHRONIC HEPATITIS B (CHB) PATIENTS SWITCHED TO TENOFOVIR ALAFENAMIDE (TAF) IN ROUTINE CLINICAL PRACTICE Ming-Lun Yeh1,2, Sam Trinh3, Chung-Feng Huang1,2, Ming-Yen Hsieh1, Ching-I Huang1,2, Po-Cheng Liang1, Jee-Fu Huang1,2, Chia-Yen Dai1,2, Wan-Long Chuang1,2, Mindie H. Nguyen3, Ming-Lung Yu1,2 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA3

接受常規臨床治療之慢性 B 型肝炎 病患轉換至 Tenofovir Alafenamide （TAF）在病毒、生化及腎臟預後之改 善 葉明倫1,2 Sam Trinh3 黃釧峰1,2 謝明彥1 黃駿逸1,2 梁博程1 黃志富1,2 戴嘉言1,2 莊萬龍1,2 Mindie H. Nguyen3 余明隆1,2 高雄醫學大學附設醫院肝膽胰內科1 高雄醫學大學醫學院醫學系2 Stanford University Medical Center, Stanford, California, USA3 Background: Clinical trial data of treatment-naïve CHB patients have reported more favorable rates of ALT normalization and safer renal profile with TAF as compared to tenofovir disoproxil fumarate (TDF), but real-world data and/or switch data are much more limited.

Aims: We aimed to investigate complete viral suppression (CVS) rate (HBV DNA＜20 IU/mL), ALT normalization rate (ALT＜40 U/L or AASLD criteria＜35/25 U/L for men/women), and renal outcomes (GFR per CKD-EPI equation, ml/ min/1.73m2) of TAF switching in routine practice.

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Methods: This retrospective study included 121 CHB patients (without hepatic decompensation or end-stage renal disease) who were switched to TAF after having been treated with another nucleot(s)ide analogue (NUC) for at least 12 months at one US and one Taiwan center.

Results: The cohort were mostly Asian (96.7%) with mean age of 55 years, 72% male, 14% cirrhosis, 21% HBeAg positive, 75% with prior TDF (mean treatment duration 51±41 months), 5.0% with entecavir (108±31 months) and others (109±42 months). At TAF switch, 13 (10.7%) patients still had detectable HBV DNA, and 62 (51.2%) had eGFR＜90. At 12 months after switch, CVS rate increased from 89.3% (108/121) to 96.2% (p=0.016). All six patients who achieved CVS after switch maintain CVS. HBeAg loss occurred in two patients (9.1%). ALT normalization also increased from 71.1% to 87.6% (p＜0.001) by local criteria (40 U/L) and from 58.7% to 70.2% (p=0.029) by AASLD criteria. Overall, the mean eGFRs were similar for the total cohort from TAF switch to the 12-month follow-up point (88.2±18.8 vs. 87.2±17.5, p=0.278). However, the subgroup of patients with CKD (eGFR＜ 90) at switch had significant improvement with a mean eGFR increase of 2.9 (p=0.027) and 16.5% (20/62) of patients experiencing at least 10% increase in eGFR during the 12-month after switch. In fact, 15.1% (8/53) of patients with CKD stage 2 and 33.3% (3/9) CKD stage 3 at switch had one CKD stage improvement.

Conclusions: In this real-world study in both East and West, prior NUC-treated CHB patients had significant improvement in viral suppression and ALT normalization rates 12-month after TAF switch. Approximately one in six patients with eGFR＜90 can expect to have a 10% improvement in eGFR 12 months after switch.

Larger and longer follow-up studies are needed to further characterize the impact on TAF switch in this population.

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P.006

THE ROLE OF HEPATITIS B CORERELATED ANTIGEN ON HBV RELAPSE AFTER CESSATION OF TENOFOVIR THERAPY IN HBEAGNEGATIVE NON-CIRRHOTIC PATIENTS Yuan-Hung Kuo1, Chien-Hung Chen1, Tsung-Hui Hu1, Jing-Houng Wang1, Chao-Hung Hung1,2, Sheng-Nan Lu1,2 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan2

B 型肝炎核心關連的抗原 e 抗原陰性 無肝硬化病人惠立妥治療停藥後預測 B 型肝炎病毒復發的角色 郭垣宏1 陳建宏1 胡琮輝1 王景弘1 洪肇宏1,2 盧勝男1,2 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科 系2 Background: It remains unclear whether HBcrAg levels could predict hepatitis B virus (HBV) relapse in chronic hepatitis B (CHB) patients who discontinued tenofovirdisoproxilfumarate (TDF) therapy.

Aims: To investigate the role of HBcrAg on HBV relapse after cessation of TDF therapy in HBeAgnegative non-cirrhotic patients.

Methods: A total of 138HBeAg-negative noncirrhotic patients who had stopped TDFtreatment for at least 12 monthswere recruited.All patients fulfilled the stopping criteriaproposed bythe Asian Pacific Association for the Study of the Liver (APASL) 2012 guideline.The serum HBcrAg levels were determined at baseline and the end of treatment.

Results: The 3-year cumulative rates of virological relapse, clinical relapse, and HBsAg loss were 72.3%, 52.6%, and 13.3%, respectively,

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after cessation of TDF therapy. The end-oftreatment HBsAg level was an independent factor of virological and clinical relapse and HBsAg loss.

HBcrAg levels at baseline and end of treatment were significant factors of virological and clinical relapse inunivariate analysis, but no in multivariate analysis. The end-of-treatment HBsAg level of 80 IU/mL and HBcrAg of 3 log U/mL were the optimal values for predicting HBV relapse after cessation of TDF therapy. The 3-year cumulative rates of virological and clinical relapse were 25.8% and 19%, respectively, in patients who achieved endof-treatment HBsAg level ≤80 IU/mL and HBcrAg ≤3 log U/mL. In contrast, the 3-year cumulative rates of virological and clinical relapse were 54.5% (P=0.094) and 47% (P=0.14), respectively, in patients who achieved end-of-treatment HBsAg level ≤ 80 IU/mL and HBcrAg＞3 log U/ mL. Furthermore, the 3-year cumulative rates of virological and clinical relapse were 91.7% and 78.4%, respectively, in patients who were end-oftreatment HBsAg level＞80 IU/mL and HBcrAg＞ 3 log U/mL. Conclusions: The combination of HBsAg andHBcrAgat the end of treatmentwas a useful marker to predict HBV relapse after discontinuation of TDF treatment.

P.007

THE ROLE OF SOLUBLE PROGRAMMED CELL DEATH PROTEIN 1 ON HBV RELAPSE AND HBSAG LOSS AFTER CESSATION OF ENTECAVIR THERAPY IN HBEAG-POSITIVE AND HBEAGNEGATIVE PATIENTS Chien-Hung Chen1, Tsung-Hui Hu1, Jing-Houng Wang1, Chao-Hung Hung1,2, Sheng-Nan Lu1,2 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan2

可溶性細胞程序性死亡蛋白 -1 在 e 抗 原陽性和陰性病人貝樂克治療停藥後 B 型肝炎病毒復發和表面抗原消失的 角色 陳建宏1 胡琮輝1 王景弘1 洪肇宏1,2 盧勝男1,2 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科2 Background: It remains unclear the change of sPD-1 levels during and post-entecavir treatment in HBeAg-positive and HBeAg-negative patients.

Aims: To investigate (1) the changes of serum sPD-1 levels during and post-entecavir therapy.

(2) the role of sPD-1 on HBV relapse and HBsAg loss after cessation of entecavir therapy.

Methods: A total of 117 HBeAg-positive and 268 HBeAg-negative non-cirrhotic patients who had stopped entecavirtreatment for at least 12 monthswere recruited.sPD-1 levels were check at baseline, end of treatment and post-treatment 6 months. All patients fulfilled the stopping criteriaproposed by APASL 2012 guideline.

Results: The mean of sPD-1 levels at baseline, end of treatment and post-treatment 6 months were 5.65±0.86, 4.69±0.69, 4.74±0.74 log pg/ mL, respectively, in HBeAg-positive patients and

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were 4.80±0.87, 4.17±0.79, 4.19±0.81 log pg/ mL, respectively, in HBeAg-negative patients.

HBeAg-positive patients had higher sPD-1 decline levels from end of treatment to baseline than HBeAg-negative patients (P=0.003). Patients without virological relapse had a higher sPD1 decline levels from end of treatment to posttreatment 6 months than those with virological relapse in HBeAg-positive (0.03±0.24 vs.

-0.13±0.47 log pg/mL, P=0.032) and HBeAgnegative patients (0.12±0.41 vs. -0.07±0.41 log pg/mL, P=0.001). The end-of-treatment sPD1 levels of 20000 and 4000 pg/mL were optimal values to predict HBV relapse in HBeAg-positive and HBeAg-negative patients, respectively. The 5-year cumulative rates of virological relapse, clinical relapse, and HBsAg loss were 31% vs.

62.8% (P=0.036), 25.1% vs. 51.4% (P=0.053), and 22.6% vs. 5.8% (P=0.013), respectively, in HBeAg-positive patients who achieved sPD-1＜ 20000 and ≥20000 pg/mL, and were 46.9% vs.

81.3% (P＜0.001), 33.1% vs. 67.4% (P＜0.001), and 41.6% vs. 9.6% (P＜0.001), respectively, in HBeAg-negative patients who achieved sPD-1＜ 4000 and ≥4000 pg/mL. Conclusions: The sPD-1 decline levels during entecavir therapy was higher in HBeAg-positive patients compared with HBeAg-negative patients.

The sPD-1 level was a useful marker to predict HBV relapse and HBsAg loss after discontinuation of entecavir treatment.

P.008

AUTOPHAGY IN TUMORS AND THE LIVER MICROENVIRONMENT STRONGLY PREDICT HEPATOCELLULAR CARCINOMA RECURRENCE AFTER CURATIVE RESECTION Chih-Wen Lin1,2,3,4, Yaw-Sen Chen4,5, Gin-Ho Lo2,4, Chia-Yen Dai6, Jee-Fu Huang6, Wang-Long Chuang6, Ming-Lung Yu6,7 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan2 Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan3 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan4 Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan5 Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan6 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan7 Background: Hepatocellular carcinoma (HCC) is currently the fifth most common type of cancer and the third leading cause of cancer-related mortality worldwide. The rate of HCC recurrence and mortality remains very high after surgical resection.

Aims: This study aimed to investigate the impact of autophagy and predictive factors on tumor recurrence and overall survival (OS) after curative resection for HCC. Methods: From 2010 to 2014, 535 consecutive HCC patients who underwent curative resection were included and followed (range, 1-84 months; median, 42 months).

Clinicopathological data, HCC recurrence and overall survival were recorded. LC3, Beclin-1, and p62 protein expression was assessed by immunohistochemistry in HCC tumors and adjacent non-tumor (ANT) tissues.

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Results: HCC recurred in 245 patients (14.4% per person-year), including 116 cases of ER and 129 cases of LR. The cumulative incidence of recurrence at 1, 3, 5 and 7 years was 9.7%, 33.9%, 53.3% and 66.3%, respectively. In multivariate analysis, HCC recurrence was significantly associated with an absence of LC3 expression in both tumors and ANT tissues, in HCC tissues only and in ANT tissues only (hazard ratio [HR]/95% confidence interval [CI]: 6.16/2.541-18.25, 5.16/1.598-16.66 and 1.88/1.288-2.740, respectively), as well as with a Child-Pugh score of B (2.61/1.379-4.925) and macrovascular invasion (1.53/1.036-2.373).

Patients negative and positive for LC3 expression showed a 5-year cumulative recurrence of 94.3% and 53.5%, respectively, in tumor and ANT tissues (p<0.001, log-rank test). Moreover, mortality was observed in 219 patients, and the cumulative incidence of overall survival at 1, 3, 5 and 7 years was 91.0%, 72.3%, 58.8%, and 27.7%. In multivariate analysis, risk of mortality was significantly associated with diminished LC3 expression in tumor and ANT tissues, HCC tissues only and ANT tissues only (hazard ratio/95% confidence interval: 6.74/2.05222.19, 6.70/1.321-33.98 and 2.58/1.499-4.915) and with recurrent HCC (5.11/3.136-8.342), HBV infection (2.75/1.574-4.784), liver cirrhosis (1.78/1.059-2.974) and the absence of antiviral therapy (0.42/0.250-0.697). The 5-year overall survival was 70.2%, 57.3%, 49.6% and 10.7%, respectively, among patients with the presence of LC3 expression in both tissues, in HCC tissues only, in ANT tissues only, and in neither of the tissues. The 5-year overall survival was 56.7%, 47.3%, 51.2% and 38.7%, respectively, among patients with HBV-related HCC, liver cirrhosis, the absence of antiviral therapy and recurrent HCC, which were significantly lower than their counterparts.

Conclusions: Patients with an absence of LC3 expression in both tumors and ANT tissues, ChildPugh score of B and macrovascular invasion was significantly associated with HCC recurrence.

Patients with HBV-related HCC, liver cirrhosis, recurrent HCC, and the absence of antiviral therapy were significantly lower overall survival.

Furthermore, Autophagy related-gene LC3 in both the tumors and liver microenvironment significantly predict HCC recurrence and overall survival after curative resection.

P.009

ASSOCIATION OF GASTRIC ACID SUPPRESSANTS AND THE DEVELOPMENT OF SPONTANEOUS BACTERIAL PERITONITIS IN CIRRHOTIC PATIENTS WITH ASCITES Shih-Lun Teng1, Jen-Chieh Huang1,2, Jeng-shiann Shin1 Division of Gastroenterology, Departments of Internal Medicine, Cheng Ching General Hospital, Taichung, Taiwan1 Department of Health Business Administration, HungKuang University, Taichung, Taiwan2

肝硬化併腹水病人使用胃酸抑制劑及 原發性腹膜炎發生之相關性 鄧世綸1 黃仁杰1,2 辛政憲1 澄清綜合醫院胃腸肝膽科1 弘光科技大學健康事業管理系2 Background: Previous studies ever found that gastric acid suppressants (GAS) was an important risk factor for spontaneous bacterial peritonitis (SBP) but some studies could not establish the relationship. Therefore, the association of GAS administration with SBP risk remains controversial.

Aims: The study aimed to characterize the association of (GAS) with the development of SBP in cirrhotic patients with ascites.

Methods: A retrospective case controlled study from January 2013 to December 2017 at ChengChing General Hospital was conducted. We included patients with a diagnosis of liver cirrhosis with ascites, divided into those with and without SBP. SBP was defined by ascites ascitic fluid polymorphonuclear cell level. GAS users were patients who received GAS daily for more than seven days in the 90 days before admission.

Results: Of 229 cirrhotic patients enrolled, 60 had SBP and 169 did not. The groups differed significantly in albumin (p=0.045) and total bilirubin (p=0.016) levels; in international normalized ratio (p=0.007) and proton pump inhibitor (PPI) use (p=0.021); but not in histamine-2 receptor

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antagonist (H2RA) use. Multivariate analysis identified PPI use as the only independent risk factor for SBP development (Odds Ratio 2.102 [95% Confidence Interval 1.126-3.925, p=0.02).

Conclusions: PPIs but not H2RAs may increase the incidence of SBP in cirrhotic patients with ascites. Prescribing PPIs in cirrhotic patients should be done carefully, for the minimal effective treatment duration.

P.010

CELL BLOCK BIOPSY OF PORTAL VEIN THROMBOSIS FOR LIVER PRE-TRANSPLANTATION EVALUATION King-Wah Chiu1,2,3, Hock-Liew Eng3,4, Yu-Fan Cheng3,5, Chao-Long Chen2,3,6 Department of Internal Medicine, Kaohsiung Chang Chang Hospital, Kaohsiung, Taiwan1 Chang Gung University College of Medicine, Kaohsiung, Taiwan2 Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan4 Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan5 Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan6

門靜脈血栓細胞塊活檢作為肝臟移植 術前評估 趙景華1,2,3 刑福柳3,4 鄭汝汾3,5 陳肇隆2,3,6 高雄長庚紀念醫院內科部1 長庚大學醫學院2 高雄長庚紀念醫院肝臟移植中心3 高雄長庚紀念醫院病理科4 高雄長庚紀念醫院放射診斷科5 高雄長庚紀念醫院一般外科6 Background: Major vessel invasion in patients with hepatocellular carcinoma (HCC) receiving living donor liver transplantation (LDLT) is one of the major factors for HCC recurrence. Malignant portal vein thrombosis (MPVT) is an absolute contraindication for liver transplantation (LT).

However, benign portal vein thrombosis (BPVT) mostly occurs in advanced liver cirrhosis patients with a slowdown of the portal vein flow. The pathological diagnosis is believable to be a tool in the pre-transplantation evaluation. Because of the small caliber of the portal vein and its location behind the common hepatic duct, conventional liver biopsy is difficult to perform in these patients.

Fine-needle aspiration cytology has been reported with regard to the differential diagnosis between

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MPVT and BPVT. Aims: We investigated 8 cases to describe the use of cell block biopsy of portal vein thrombosis (PVT) for the pre-transplantation evaluation in patients on our waiting list for LDLT. Methods: From December 2016 to March 2019, 8 patients with HCC (hepatitis B virus-related liver cirrhosis in 5 patients and hepatitis C virus in 3) had been receiving optimal treatments previously and were complicated with PVT. Their mean age was 58.1 years (range, 46–65 years), and all of them were men. All PVTs were documented by Doppler ultrasonography, computed tomography angiography, and magnetic resonance imaging studies. The right side was affected in 4 cases, and umbilical portion of the portal vein was affected in the other 4 cases. Using a sonography-guided Chiba needle (22 gauge, 15 cm), aspiration was performed via the right intercostal space, and segment 5 of the liver was obliquely puncture to avoid injuring the common hepatic duct in the case of right PVT. For the umbilical portion in PVT, a vertical puncture was performed via segment 4 of the liver. The needle tip was suctioned within the lumen of the portal vein, and bloody material was obtained. The specimen was fixed with a formalin solution and centrifuged at 3000 rpm for 3 minutes, dressed in liquid paraffin during the embedding procedure for an additional 0.6-µm section, and finally, stained using hematoxylin and eosin, as described in our previous study.

Results: Seven MPVTs were identified by the cell block histological study and withdrawn for further LT. Only one BPVT was diagnosed and that patient received LDLT subsequently. There was no evidence of HCC recurrence for 6 months of follow-up until now. In our case series, no complication associated with ultrasonographyguided 22-gauge Chiba needle puncture of the PVT was observed.

Conclusions: Cell block biopsy of PVT is a histological interpretation from the fine-needle aspiration procedure. In the LT setting, Menghini needle biopsy was used to identify the liver parenchyma and tumor pathology in our LT program. Because of the small caliber of the portal vein lumen, even the one-fire biopsy gun or Menghini needle was not appropriate for approaching the portal vein. If the biopsy needle penetrates from the liver parenchyma to the

portal vein, the pathological interpretation will be challenging, as it will be unclear whether the tissue was obtained from the parenchyma or from inside of the portal vein. However, when using the cytology study, it is difficult to identify welldifferentiated cell grading of HCC. The specific trabecular cellular arrangement is a typical finding for diagnosing HCC. High-force centrifugation should be performed again to evaluate the trabecular pattern from the separated single cells in our current study.Based on the ultrasonographic view, the location of the common hepatic duct was in front of the right portal vein; therefore, we were able to puncture the abdominal surface obliquely at 45 degrees to avoid injuring the common hepatic duct. Cell block biopsy of portal vein thrombosis may be a safety and accurate way to identify MPVT or BPVT during the liver pre-transplantation evaluation.

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P.011

DRUG-DRUG INTERACTION OF ELBASVIR/GRAZOPREVIR TREATMENT FOR CHRONIC HEPATITIS C IN TAIWAN Pin-Nan Cheng1, Chun-Jen Liu2, Kuo-Chih Tseng3, Ching-Chu Lo4, I-Hao Tseng5 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine Taipei, Taiwan2 Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzu Chi University, Hualien, Taiwan3 Department of Internal Medicine, St. Martin de Porres Hospital, Chia-Yi, Taiwan4 Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan5

Elbasvir/Grazoprevir 於台灣治療 C 肝患者藥物交互作用之分析 鄭斌男1 劉俊人2 曾國枝3 羅清池4 曾翊豪5 國立成功大學醫學院附設醫院內科部1 國立臺灣大學醫學院附設醫院內科部2 大林慈濟醫院內科部肝膽胃腸科3 聖馬爾定醫院內科部4 阮綜合醫院內科部5 Background: The assessment of drug-drug interaction (DDI) is important not only for safety but also for maintaining the efficacy of direct acting antivirals in chronic hepatitis C (CHC).

Aims: This study aims to evaluate DDI before and during elbasvir/grazoprevir (EBR/GZR) treatment.

Methods: CHC patients who treated with EBR/ GZR in five hospitals were enrolled. The patients’ demographic data, comorbidities, concomitant medications taken before and during EBR/ GZR were recorded. DDI was evaluated using a tool from the HEP Drug Interactions (www.hepdruginteractions.org) website. In addition to the

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evaluation of DDI for EBR/GZR, the virtual DDI of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/ velpatasvir (SOF/VEL) and glecaprevir/ pibrentasvir (GLE/PIB) were evaluated. Degrees of DDI were classified as “do not co-administer”, “potential interaction”, and “potentially weak interaction”.

Results: A total of 460 patients were enrolled.

At baseline, 80.1% of patients had one or more comorbidities and 72.8% took one or more medications. Cardiovascular diseases (43.9%), gastrointestinal diseases (37.4%), and metabolic diseases (36.7%) were the three most common comorbidities. The prevalence of DDI before EBR/GZR treatment was 12.8% (59 patients).

Among the same population, the prevalence of virtual DDI of SOF/VEL, GLE/PIB, and LDV/SOF were 38.5% (179 patients), 48.8% (220 patients), and 57.0% (262 patients), respectively. During EBR/GZR treatment, 167 patients (36.3%) took newly prescribed medications. One patient (0.2%) and seven patients (1/5%) exhibited do-not-coadminister and potential interaction with EBR/ GZR, respectively.

Conclusions: DDI was limited in treatment with EBR/GZR. DDI can occur upon the administering of a new medication during antiviral treatment and attention should be paid to it.

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P.012

EFFICACY AND SAFETY OF DIRECT ANTIVIRAL AGENT TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C IN SOUTHERN TAIWAN: REAL-WORLD EXPERIENCE IN PINGTUNG COUNTY Shi-Chi Wen1, Wu-Hsien Kuo2, Lung-Chih Cheng1, Hsin-Wen Lai1, Chi-Chang Tsai3, Jyan-Wei Huang3 Division of Gastroenterology, Department of Internal Medicine, Pao-Chien Hospital, Pingtung, Taiwan1 Yuan-Sheng Hospital, Changhua, Taiwan2 Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan3

慢性 C 型肝炎患者接受直接抗病毒治 療在屏東地區之真實世界效果及安全 性

hospital, Ping-Tung from Apr 2017 to Jan 2019.

In total, 32 patients were treated, 40.6% had cirrhosis, 56.3% had genotype 1b and 3.1% had mixed infection (genotype 1+6) in dual therapy group. The rate of SVR among patients was 96.7% in per-protocol population (PP) and 90.6% in intent-to -treat (ITT) population. Two patients discontinued owing to intolerance. The most common events were headache, nausea and fatigue. The prevalence of SVR (PP) was higher among patients with single infection than among patients with mixed infection (96.7% vs. 0.0%, P ＜0.001). In the univariate analysis by logistic regression, the negative predictive factor of an SVR in PP population was the mixed infection (OR: 0.034; P=0.01).

Conclusions: DAAs treatment provided higher rates of sustained virological response for HCV infection based on HCV genotype specific and individualized approaches.

文士祺1 郭武憲2 鄭隆致1 賴欣汶1 蔡奇璋3 黃健維3 屏東寶建醫院內科部胃腸肝膽科1 員林員生醫院2 國軍高雄總醫院內科部胃腸肝膽科3 Background: Therapies for hepatitis C (HCV) are evolving rapidly with the advent of novel of directacting antiviral agent (DAA). Safe and effective HCV therapies have led to tremendous advances in HCV care with DAA that target HCV-specific proteins.

Aims: We review evidence for current therapeutic options for HCV infection based on HCV genotype-specific and individualized approaches.

Methods: We conducted a retrospective cohort study. Patients with HCV infection were treated with Declatasvir (Daklinza) & Asunaprevir (Sunvepra) for genotype 1b, Ombitasvir/ paritaprevir/ritonasvir (Viekirax) & dasabuvir (Exviera) for genotype 1, Elbasvir/grazoprevir (Zepatier) for genotype1,4, Sofosbuvir/ledipasvir (Harvoni) for genotype 1, 2, 4, 5, 6, Sofosbuvir (Sovaldi) combined ribavirin for genotype 2 and Glecaprevir/pibrentasvirhave (Maviret) for genotype 1, 2, 3, 4, 5, ,6. The primary end point was a sustained virological response (SVR) at 12 weeks after the end of therapy.

Results: We enrolled patients at Pao-Chien

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P.013

INCREASING AGE AND NON-LIVER COMORBIDITIES IN PATIENTS WITH CHRONIC HEPATITIS B IN TAIWAN: A NATIONWIDE POPULATIONBASED ANALYSIS Cheng-HaloTseng1, Yao-Chun Hsu2, Hsiu J. Ho3, Chun-Ying Wu3 Devision of Gastroenterology and Hepatology, E-DA cancer Hospital/I-Shou University, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan2 Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan3

慢性 B 型肝炎病人族群之年齡及非肝 臟相關共病都在增加中：一全國性的 調查分析 曾政豪1 許耀峻2 何秀榮 3 吳俊穎3 義大癌治療醫院胃腸肝膽科1 義大醫院胃腸肝膽科2 臺北榮民總醫院轉譯醫學科3 Background: How the burden of non-liver comorbidity changed over time in patients with chronic hepatitis B (CHB) remains incompletely understood.

Aims: The study aimed to characterize the temporal changes in age and non-liver comorbidity between 2001 and 2011 among CHB patients in Taiwan.

Methods: This study analyzed Taiwan National Health Insurance Research Database (NHIRD) to identify adult (≥18 years) patients who were diagnosed with CHB (at least one inpatient or two outpatient claims for a known diagnosis of CHB) in 2001, 2006, and 2011. The changes in demographic features, prevalence of nonliver comorbidities, and exposure to medications with potential harmful effects over the decade were examined. Patients without a diagnosis of CHB from inception to December 31, 2011 were randomly selected from the general population as non-CHB controls. Diseases status was coded according to International Classification of Diseases, Ninth Revision.

Results: A total of 102,158, 252,809, and

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338,200 eligible CHB patients were identified in 2001, 2006, and 2011, respectively. The median age significantly advanced from 44.5 in 2001 to 51.9 years in 2011 (p＜0.001). The prevalence of comorbidities including Charlson comorbidity index, diabetes mellitus, hypertension, dyslipidemia, stroke, heart failure, malignancy other than liver cancer, chronic kidney disease, and bone fracture all significantly increased from 2001. The exposure to aspirin, non-steroidal antiinflammatory drug, and steroid also increased over time. Moreover, the chronological changes in age, metabolic and cardiovascular comorbidities were significantly more pronounced in CHB patients as compared with the non-CHB controls.

Conclusions: The CHB population in Taiwan have aged and presented with a higher non-liver comorbidity burden over a decade. These findings may inform the management of CHB in treatment selection and safety monitoring.

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P.014

BONE AND RENAL SAFETY ARE IMPROVED IN CHRONIC HBV PATIENTS SWITCHED TO TENOFOVIR ALAFENAMIDE (TAF) AFTER EITHER 2 OR 3 YEARS OF PRIOR TENOFOVIR DISOPROXIL FUMARATE (TDF) TREATMENT Wan-Long Chuang1, Maria Buti 2, Namiki Izumi3, Young-Suk Lim4, Harry LA Janssen5, Jia-Horng Kao6, Adrian Streinu-Cercel7, Elena Nurmukhametova8, Xiaoli Ma9, Fehmi Tabak10, Maciej Jablkowski11, Vithika Suri12, John F. Flaherty12, Audrey Lau12, Anuj Gaggar12, Shuyuan Mo12, Abhijit Chowdhury13, Scott Fung5, Ed Gane14 Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan1 Hospital Universitari Vall d’Hebron, Barcelona, Spain2 Japanese Red Cross Musashino Hospital, Tokyo, Japan3 University of Ulsan College of Medicine, Seoul, South Korea4 Toronto Center for Liver Disease, University of Toronto, Ontario, Canada5 National Taiwan University College of Medicine and Hospital, Taipei City, Taiwan6 National Institute for Infectious Diseases, Universitatea de Medicină și Farmacie “Carol Davila,” București, Romania7 Clinic Tour, Moscow, Russia8 Hahnemann University Hospital, Philadelphia, Pennsylvania, USA9 Cerrahpaşa Tıp Fakültesi, İstanbul Üniversitesi‒Cerrahpaşa, Istanbul, Turkey10 Uniwersytet Medyczny w Łodzi, Poland11 Gilead Sciences, Inc, Foster City, California, USA12 Institute of Post Graduate Medical Education and Research, Kolkata, India13 Auckland City Hospital, Auckland, New Zealand14 Background: TAF, a novel prodrug of tenofovir, has shown similar efficacy to TDF in Phase 3 studies with less bone and renal effects. As part

of a protocol amendment to extend double blind (DB) treatment for 1 additional year (Week 96 to Week 144), only ~50% consented in time for this change; the remainder had already been receiving open-label (OL) TAF after Week 96.

Aims: Here, we evaluate the 4 year (Week 192) safety and efficacy of switching to OL TAF in patients who had received DB TDF treatment for either 2 or 3 years.

Methods: In 2 identically-designed studies, 1298 HBeAg-negative and HBeAg-positive CHB patients (873 TAF, 425 TDF) were randomized and treated with either TAF or TDF. In the TDF group, 180 patients were switched to OL TAF at Week 96 (OL TAF 96 Wk), while 202 patients switched from DB TDF to OL TAF at Week 144 (OL TAF 48 Wk). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG]) parameters, viral suppression, and biochemical responses were assessed at Week 192 using the time of rollover to TAF as the respective OL baseline (BL). Within group changes in bone and renal parameters were assessed by paired t test or Wilcoxon signed rank test.

Results: Patient characteristics were similar for those receiving OL TAF for 1 or 2 years following DB TDF treatment. Significant increases in eGFRCG from OL BL were observed within each group at Week 192 (Table). Significant increases in hip and spine BMD from OL BL occurred within each group, the magnitude was greater after 2 years of OL TAF only for hip BMD. Within each group, virologic suppression (HBV DNA＜29 IU/ mL) was maintained from OL BL to Week 192 in patients who remained on TAF treatment (OL TAF 96 Wk group: 88% and 88%; OL TAF 48 Wk group: 94% and 93%, respectively), while at Week 192, within each group the rate of ALT normalization by 2018 AASLD criteria increased from OL BL after switching to TAF (55% OL TAF 96 Wk and 37% OL TAF 48 Wk).

Conclusions: In CHB patients treated with TDF for 2 or 3 years, recovery of renal and bone parameters occurred at Year 4 suggesting reversibility of these parameters. Virologic control was maintained and ALT normalization increased following the switch from TDF to TAF.

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P.015

EFFICACY AND SAFETY OF SOFOSBUVIR/VELPATASVIR FOR THE TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE 1-6 INFECTION: INTEGRATED ANALYSIS OF EIGHT PHASE 3 CLINICAL TRIALS Stephen D. Shafran1, Jordan J. Feld2, Ira M. Jacobson3, Ola Weiland4, Ajit Sood5, Stuart C. Gordon6, Eric Lawitz7, Kris Mar8, Darya Habibi8, Nelson Cheinquer8, Stacey Lee8, Joseph Llewellyn8, Gerald Crans8, Hongmei Mo8, Mark Sulkowski9 University of Alberta, Edmonton, AB, Canada1 Toronto Western Hospital Liver Centre, Toronto, Ontario, Canada2 NYU School of Medicine, New York3 Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden4 Dayanand Medical College, Ludhiana, Punjab, India5 Department of Gastroenterology, Henry Ford Hospital, Detroit, MI6 Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas7 Gilead Sciences, Inc, Foster City, California8 Johns Hopkins University, Baltimore, Maryland9 Background: The World Health Organization (WHO) estimates that 71 million people are chronically infected with the hepatitis C virus (HCV) worldwide, and has a goal to eliminate this disease as a public health threat by 2030.

The once-daily single tablet regimen (STR) sofosbuvir/velpatasvir (SOF/VEL) is a PI-free, pangenotypic, panfibrotic, single duration regimen for the treatment of HCV offering a simplified option to address this elimination goal. This 12 week regimen can be used irrespective of viral genotype, viral load, fibrosis status or HIV coinfection status.

Aims: This integrated analysis of phase 3 clinical trials evaluates the safety and efficacy of SOF/ VEL for 12 weeks in patients with HCV across all genotypes (GT) and fibrosis stages, including patients with compensated cirrhosis and HIV/HCV coinfected participants.

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Methods: Analysis of safety and efficacy data for HCV GT 1-6 treated with SOF/VEL for 12 weeks without ribavirin from eight phase 3 clinical studies (ASTRAL-1, -2, -3, -5, POLARIS-2, -3, GS-3421522; and GS-342-1521). Results are reported on an intention-to-treat analysis.

Results: Overall, 1938 patients with HCV GT1-6 were included. The mean age was 52 years, 61% were male, mean BMI was 26.6 kg/m2, and 5% were HIV/HCV coinfected. Genotype distribution was: 38% GT1, 16% GT2, 32% GT3, 14% GT46. Advanced fibrosis (F3 or F4) was present in 822 (42%) patients, including 496 (26%) with compensated cirrhosis. The study also included 494 (25%) treatment experienced patients.

Overall, 98% of the patients achieved sustained virologic response (SVR), with ≥95% across all genotypes including patients with compensated cirrhosis and 95% in HIV/HCV coinfected patients.

SOF/VEL was well-tolerated, with adverse events (AEs) reported in＞5% of patients including headache (24%), fatigue (19%), and nausea (10%). Grade 4 laboratory abnormalities were identified in＜1% of the patients.

Conclusions: SOF/VEL STR for 12 weeks is a simple, highly effective, and well-tolerated treatment for HCV GT1-6 patients. These data support current AASLD/IDSA, EASL, and WHO recommendations for HCV treatment using SOF/ VEL in GT1-6 patients.

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P.016

SOFOSBUVIR/VELPATASVIR FOR 12 WEEKS IS SAFE AND EFFECTIVE IN PATIENTS UNDERGOING DIALYSIS Sergio M Borgia1, Janet Dearden2, Yoav Lurie3, Stephen D Shafran4, Ashley Brown5, Kris Mar6, Robert Hyland6, Sophia Lu6, Svetlana Markova6, Hadas Dvory-Sobol6, Anu O Osinusi6, Eric M Yoshida7, Jose Luis Calleja8, Edward J Gane9 William Osler Health System1 Saint Bartholomew’s Hospital2 Shaare Zedek Medical Center3 Deaprtment of Medicine, University of Alberta4 Imperial College Healthcare NHS Trust5 Gilead Sciences, Inc.6 Gordon and Leslie Diamond Health Care Centre7 Hospital Universitario Puerta De Hierro8 Auckland City Hospital9 Background: Approved HCV treatments for patients on dialysis are associated with complexities including drug-drug interactions, baseline resistance testing, use of ribavirin, and risk of hepatotoxicity. Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS-331007, in severe renal impairment, real-world case series demonstrated substantial use of SOFbased regimens in this population with no safety concerns identified.

Aims: This study evaluated the safety, efficacy, and pharmacokinetics (PK) of SOF/velpatasvir (VEL) for 12 weeks in patients with HCV infection on dialysis.

Methods: Treatment-naïve or -experienced patients, of any genotype, with or without compensated cirrhosis undergoing hemodialysis or peritoneal dialysis, were enrolled to receive open-label SOF/VEL (400 mg /100 mg daily) fixed-dose combination once daily for 12 weeks.

The primary efficacy endpoint was comparison of the sustained virologic response 12 weeks after treatment (SVR12) to a prespecified historic control rate of 83%. The primary safety endpoint was the proportion of patients who discontinued therapy due to adverse events (AEs). Secondary endpoints included safety, viral resistance, and

PK. Results: 59 patients were enrolled at 21 sites in Canada, United Kingdom, Spain, Israel, Australia and New Zealand. The median age was 62 years (range 49-86), 59% were male, 53% white, 32% treatment experienced, 29% had cirrhosis. Most patients had HCV genotype 1 (42%), 2 (11%), or 3 (27%). Most (92%) were on hemodialysis with a mean (range) dialysis duration of 7.3 years (0 – 40). Treatment was well tolerated; no one discontinued therapy due to AEs. One patient was discontinued therapy on day 74 for noncompliance with 48% study medication adherence by pill count. Overall, 56/59 (95%) of patients achieved SVR12. Two (3%) had virologic relapse (one with non-adherence). One patient did not achieve SVR12 due to death from suicide after SVR4. Exposures were consistent with the Phase 1 renal impairment study. The most frequent AEs were headache, fatigue, nausea, and vomiting.

Serious adverse events occurred in 19% of patients, none was assessed as related to study drug.

Conclusions: Treatment with SOF/VEL single tablet regimen for 12 weeks in patients with and without cirrhosis undergoing dialysis resulted in a 95% SVR12 rate. The regimen was safe and well-tolerated with no treatment related discontinuations or treatment-related SAEs.

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P.017

SOFOSBUVIR/VELPATASVIR IS EFFECTIVE AND SAFE IN PATIENTS WITH CONCOMITANT PROTON PUMP INHIBITOR USE IN CLINICAL STUDIES Rafael Esteban1, Kosh Agarwal2, Jose Luis Calleja3, Jean-Francois Dufour4, Steven L. Flamm5, Stuart C. Gordon6, Kris Mar7, Luisa M. Stamm7, Liyun Ni7, Diana M.Brainard7, Kris V. Kowdley8, Curtis Cooper9, Juan Antonio Pineda10, Lluis Castells1, Maria Buti1, Sabela Lens11 Vall D’hebron University Hospital1 King’s College Hospital NHS Trust2 Hospital Universitario Puerta De Hierro3 University of Bern4 Northwestern University Health System5 Henry Ford Health System6 Gilead Sciences, Inc.7 Swedish Medical Center8 The Ottawa Hospital, Canada9 Hospital Universitario Virgen De Valme10 University of Barcelona11 Background: Prior to the availability of Phase 1 drug interaction data, concomitant proton pump inhibitor (PPI) use was prohibited in clinical trials of sofosbuvir/velpatasvir (SOF/VEL). Later clinical studies allowed for the use of up to 20 mg omeprazole or equivalent dosing.

Aims: This analysis evaluated the efficacy and safety of patients with and without compensated cirrhosis who received SOF/VEL for 12 weeks and reported concomitant use of a PPI. Methods: This was a retrospective analysis of efficacy and safety data from 12 Phase 2 and Phase 3 clinical studies in which patients of all genotypes with and without compensated cirrhosis received 12 weeks of SOF/VEL and reported concomitant use of a PPI. Efficacy was assessed by SVR12 and relapse rates and safety was assessed by treatment-emergent adverse events (AEs).

Results: 87 patients reported concomitant use of a PPI. The mean age (range) was 57 years (26-78), 79% were male and 75% were white; 56% of patients were infected with genotype 3 and 29% with genotype 1; 37% of patients had compensated cirrhosis and 39% were treatment

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experienced. The most common PPI was omeprazole reported by 68% of patients. The SVR12 rate was 97% (84 of 87 patients). Of the 3 patients who did not achieve SVR12, 2 patients relapsed (relapse rate 2%) and one patient with a history of diabetes discontinued SOF/VEL after 7 days of dosing due to hyperglycemia. No other patient had an AE which led to discontinuation or interruption of SOF/VEL. 78% of patients had an AE, most of which were mild, and 11% had a serious AE. These efficacy and safety are comparable to patients enrolled in the same studies who received SOF/VEL for 12 weeks without concomitant use of a PPI (SVR12 rate 97% [2445 of 2517 patients]; relapse rate 2% [40 of 2488 patients]).

Conclusions: In Phase 2 and Phase 3 clinical studies, the single-tablet regimen of SOF/ VEL for 12 weeks was effective and safe in patients with concomitant PPI use. These data support the use of SOF/VEL according to labeled recommendations with respect to coadministration of PPIs and other acid reducing agents.

2019 TDDW

P.018

SOFOSBUVIR/VELPATASVIR FOR 12 WEEKS IN GENOTYPE 1-4 HCVINFECTED LIVER TRANSPLANT RECIPIENTS Kosh Agarwal1, Luis Castells2, Beat Müllhaupt3, Douglas C. MacDonald4, Kris Mar5, Brian McNabb5, Sarah Arterburn5, Gregory Camus5, John McNally5, Diana M Brainard5, G. Mani Subramanian5, Enoka Gonsalkorala1, Maria Londoño6, Jean-François Dufour7, Xavier Forns6 Kings College Hospital NHS Trust Foundation, London, UK1 Hospital Universitario Val d’Hebron, Barcelona, Spain2 University Hospital Zurich, Zurich, Switzerland3 University College London, London, UK4 Gilead Sciences Ince, Foster City, CA, USA5 Hospital Clinic de Barcelona, CIBEREHD and IDIBAPS, Barcelona, Spain6 University of Bern, Bern, Switzerland7

used tacrolimus, 24% mycophenolic acid, 14% cyclosporine, 11% azathioprine, 10% sirolimus, 6% everolimus, and 1% prednisolone. Median (range) time from liver transplantation was 7.5 (0.3-23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). There were 62 (78%) patients with adverse events (AEs). Common (＞10%) AEs were headache (24%), fatigue (20%), and cough (10%). One patient discontinued SOF/VEL on Day 7 due to an AE of grade 1 hyperglycemia.

No serious or severe AEs were assessed by the investigator as related to SOF/VEL, there were no episodes of liver transplant rejection, and there were no deaths.

Conclusions: Treatment with the single tablet regimen of SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis.

Background: Treatment with SOF/VEL for 12 weeks results in high sustained virologic response rates 12 weeks after treatment (SVR12) in genotype 1-6 HCV infected patients in clinical trials and real-world settings.

Aims: The current study evaluated the safety and efficacy of SOF/VEL in adult patients with recurrent chronic genotype (GT) 1-6 HCV infection post-liver transplant.

Methods: This Phase 2, single-arm, openlabel study evaluated 12 weeks of SOF/VEL 400/100mg daily for 12 weeks in HCV-infected liver transplant recipients in Spain, the United Kingdom, and Switzerland. Patients could be treatment experienced or treatment naïve with no cirrhosis or compensated cirrhosis, and had to be ≥ 3 months post-transplant with no signs of rejection at screening and a history of pretransplant chronic HCV. The primary endpoint was SVR12.

Results: A total of 79 patients were enrolled and treated. Of these, 81% were male, 82% were white, 9% had compensated cirrhosis, 59% were treatment-experienced, 47% had GT1, 4% GT2, 44% GT3, and 5% GT4 HCV infections.

For immunosuppression, 71% of patients

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2019 TDDW

P.019

CLINICAL UTILITY AND APPLICATION OF NONINVASIVE TESTS IN SELECTING PATIENTS WITH ADVANCED FIBROSIS DUE TO NASH IN THE PHASE2 ATLAS TRIAL Jia-Horng Kao1, Rohit Loomba2, Naim Alkhouri3, Simone Strasser4, Vincent Wai-Sun Wong5, Raul Aguilar Schall6, Bryan J. McColgan6, G. Mani Subramanian6, C. Stephen Djedjos6, Robert P. Myers6, Zachary Goodman7, Aasim Sheikh8, Guy Neff9, Bal Bhandari10, Nadege Gunn11, Kris Kowdley12 National Taiwan University, Taipei, Taiwan1 University of California San Diego, La Jolla, CA, USA2 Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA3 University of Sydney, Sydney, NSW, AUS4 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong5 Gilead Sciences, Inc., Foster City, CA, USA6 Inova Fairfax Hospital, Falls Church, VA, USA7 GI Specialists of Georgia, Marietta, GA, USA8 Florida Research Institute, Lakewood Ranch, FL, USA9 Delta Research Partners, Bastrop, LA, USA10 Pinnacle Clinical Research, Austin, TX, USA11 Swedish Medical Center, Seattle, WA, USA12 Background: Liver biopsy is a barrier to clinical trial enrollment in NASH. Aims: We describe the utility of noninvasive tests (NITs) to enroll patients with advanced fibrosis (F3-F4) due to NASH. Methods: The ATLAS study (NCT03449446) enrolled patients based on: 1) a biopsy showing F3-F4 fibrosis per the NASH CRN classification (the biopsy cohort); or 2) in the absence of a prior biopsy, an ELF test ≥9.8 and liver stiffness (LS) by transient elastography (TE; FibroScan) ≥14.0 kPa using the XL probe (the NIT cohort). Patients in the NIT cohort had baseline biopsies and were randomized regardless of results. Analyses are based on an interim data cut.

Results: Of the 645 screened patients with

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evaluable fibrosis stage (median age 59 years, 62% women, 61% with diabetes, median BMI 33.7 kg/m2), 395 were enrolled. Fifty-five (14%) qualified based on NIT criteria; F3-F4 fibrosis was confirmed in 87% (48/55) (4% F0, 4% F1, 5% F2, 22% F3, 65% F4). Patients in the biopsy cohort with F3-F4 fibrosis had demographics, liver biochemistry, and serum fibrosis markers similar to those in the NIT cohort, but with higher LS by TE (Table). The proportions of patients with NAS ≥4 (87% vs 86%) and cirrhosis (65% vs 53%; p=0.09) did not differ between the NIT and biopsy cohorts. Within the NIT cohort, biopsy length was shorter in patients with F0-F2 vs F3-F4 (1.3 vs 2.2 cm; p=0.18). Patients with F0-F2 fibrosis also had lower BMI (31.0 vs 34.4 kg/m2; p=0.11), less diabetes (43% vs 75%), and less lobular inflammation and ballooning.

Conclusions: In this Phase 2 trial of patients with NASH, a combination of ELF and LS by TE identified the target population in 87% of patients.

Enrollment based on NITs should be considered for future NASH studies to reduce reliance on biopsy.

2019 TDDW

P.020

ACTIVE HEPATOCELLULAR CARCINOMA WAS ASSOCIATED WITH DIRECT-ACTING ANTIVIRALS TREATMENT FAILURE: A RETROSPECTIVE STUDY WITH PROSPECTIVELY COLLECTED DATA Yi-Hao Yen, Sheng-Nan Lu, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Chien-Hung Chen

CI 4.4-136.9], P＜0.001). Further, we excluded 23 patients with active HCCs from multivariate analysis. After adjustment for confounders, inactive HCCs (versus non-HCC) was not associated with non-SVR (AOR 3.1 [95% CI 0.949.95], P=0.06).

Conclusions: Active HCCs was associated with non-SVR while inactive HCCs was not. We suggest deferral of DAA treatment after complete radiological response of HCCs treatment.

Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

未治療完全的肝癌和 C 肝全口服藥物 治療失敗有關 顏毅豪 盧勝男 胡琮輝 王景弘 洪肇宏 陳建宏 高雄長庚紀念醫院胃腸肝膽科 Background: Previous studies from western countries reported that active hepatocellular carcinoma (HCC) was associated with directacting antivirals (DAA) treatment failure.

Aims: We aim to examine this issue in an Asian cohort.

Methods: A retrospective cohort study was conducted on advanced fibrotic patients who were treated for hepatitis C virus (HCV) with DAAs at our institution between January 2017 and July 2018.

Results: We have treated 1021 HCV-infected patients during this period. After exclude 42 patients who did not complete treatment course, 1 patient who completed treatment but refused to follow, 1 patient with HCC combined cholangiocarcinoma, 1 patient with virologic relapse due to malpractice. A total of 976 patients were enrolled into per protocol analysis, 556 (57.2%) patients were genotype 1b, 314 (32.3%) patients were genotype 2, 781 patients without HCCs, 172 patients with inactive HCCs and 23 patients with active HCCs. Non-SVR was 2.9% in patients with inactive HCCs, 13.0% in patients with active HCCs and 1.3% in patients without HCCs. After adjustment for confounders, active HCCs (versus inactive HCCs and non-HCC) was associated with non-SVR (AOR 24.5 [95%

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2019 TDDW

P.021

HIGH FAT DIET INDUCED CHRONIC KIDNEY DISEASE PROGRESSION IN NASH MICE Hung-Cheng Tsai2, Ying-Ying Yang2,3, Kuei-Chuan Lee1,3, Yun-Cheng Hsieh1,3, Yi-Hsiang Huang1,3, Han-Chieh Lin1,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2 Institute of Clinical Medicine, Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan3

高脂飼料誘發非酒精性肝炎老鼠慢性 腎衰竭之進展 蔡弘正2 楊盈盈2,3 李癸汌1,3 謝昀臻1,3 黃怡翔1,3 林漢傑1,3 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院內科部2 國立陽明大學臨床醫學研究所3 Background: Identification of new pharmacological approaches to inhibit the excessive fat intake-induced steatohepatitis and chronic kidney disease (CKD) is importance.

High-fat diet (HFD) intake and obesity have been associated with onset and progression of steatohepatitis and chronic kidney disease, the common pathogenesis has not yet been explored in mice with steatohepatitis.

Aims: This study aims to evalaute the chornic renal disease development and progression in high-fat diet fed mice with NASH. Methods: Male C57BL/6 mice were provided with normal chow as NC group or a high-fatdiet (HFD, 60% kcal in fat) as HFD groups. The groups of C57BL/6 mice included NC-24w group (n=5)/HFD-24w group (n=8) continuously fed NC/ HFD for 24-weeks, at which time steatohepatitis, albuminuria, and a decrease in GFR developed.

At the end of 24-weeks, we compared both group’s blood pressure, metabolic demands and renal function; basal measurements like glucose tolerance test (GTT); serum and tissue metabolic and inflammatory profiles. Histologic analysis like nonalcoholic fatty liver disease activity score (NAS) was measured. We measured various

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proteins and mRNAs in podocytes/HK-2 cell lysates, glomerular and tubular fractions of renal homogenates; albumin endocytosis or albumin re-uptake of HFD-sera-pretreated podocytes and HK-2 cells; SIRT1-autophagy protein and mRNA levels in cultured podocyte and HK-2; apoptotic and barrier markers podocytes and HK-2 cells.

Results: After 24 weeks HFD intake, hemodynamic and morphological changes, together with other factors such as systemic inflammation, oxidative stress, metabolic dyshomeostasis, result in steatohepatitis and CKD and ultimately lead to cirrhosis and ESRD. The perioxisome proliferator-activated receptors (PPAR)-α and PPARδ are crucial for the regulation of inflammation, oxidative stress and metabolic dys-homeostasis in obese individuals with steatohepatitis. PPARα agonists attenuate albuminuria and renal fibrosis in diabetic animals.11 In diabetes mice, down-regulated renal PPARδ expressions results in heavy albuminuria, renal inflammation and fibrosis Conclusions: Altogether, 24 weeks high fat diet intake lead to both steatohepatitis and CKD, PPARα/δ was the common pathogenesis for both diseases.

2019 TDDW

P.022

ELAFIBRANOR INHIBITS CHRONIC KIDNEY DISEASE PROGRESSION IN NASH MICE Hung-Cheng Tsai2, Ying-Ying Yang1,3, Kuei-Chuan Lee1,3, Yi-Hsiang Huang1,3, Ming-Chih Hou1,3, Han-Chieh Lin1,3 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2 Institute of Clinical Medicine, Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan3

Elafibranor 抑制非酒精性肝炎大鼠慢 性腎衰竭的惡化 蔡弘正2 楊盈盈1,3 李癸汌1,3 黃怡翔1,3 侯明志1,3 林漢傑1,3 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院內科部2 國立陽明大學臨床醫學所3 Background: High-fat diet (HFD)-induced steatohepatitis and CKD share common pathogenesis involving peroxisome proliferatoractivated receptor (PPAR)-α and -δ. Elafibranor, a dual PPARα/δ agonist, can ameliorate the HFD-induced steatohepatitis. Nonetheless, it effects of HFD-induced CKD had not yet explored.

Aims: This study evalute the effects of chronic elafibronor treatment for the progression of NASH-related CKD. Methods: Male C57BL/6 mice were provided with normal chow as NC group or a high-fat-diet (HFD, 60% kcal in fat) as HFD groups. The groups of C57BL/6 mice included NC-24w group (n=5)/ HFD-24w group (n=8) continuously fed NC/HFD for 24-weeks were administered vehicle for 12week from 13th to 24th week of NC/HFD feeding; HFD-elaf group (n=8) continuously fed HFD for 24-weeks were administered elafibranor for 12week from 13th to 24th week of HFD feeding, at which time steatohepatitis, albuminuria, and a decrease in GFR developed. This dose has been demonstrated previously to decrease the progression of steatohepatitis. At the end of 24-weeks, we compared both group’s blood pressure, metabolic demands and renal function;

basal measurements like glucose tolerance test (GTT); serum and tissue metabolic and inflammatory profiles. Histologic analysis like nonalcoholic fatty liver disease activity score (NAS) was measured. We measured various proteins and mRNAs in podocytes/HK-2 cell lysates, glomerular and tubular fractions of renal homogenates; albumin endocytosis or albumin re-uptake of HFD-sera-pretreated podocytes and HK-2 cells; SIRT1-autophagy protein and mRNA levels in cultured podocyte and HK-2; apoptotic and barrier markers podocytes and HK-2 cells.

Results: In vivo and in vitro renal effects were evaluated in HFD-elaf mice receiving 12 week of elafibranor (from 13th to 24th week of HFD feeding) treatment. In elafibranor-treated HFD mice, increased insulin sensitivity, reduced obesity and body fat mass, decreased severity of steatohepatitis, increased renal expression of PPARα, PPARδ, SIRT1, and autophagy (Beclin-1 and LC3-II) as well as glomerular/renal tubular barrier markers [synaptopodin (podocyte marker), zona occludin-1 and cubulin], reduced renal oxidative stress and caspase-3, and less urinary 8-isoprostanes excretion, were observed.

Aforementioned benefits of elafibranor were associated with low renal tubular injury and tubulointerstitial fibrosis scores, less albuminuria, low urinary albumin-to-creatinine ratio, and preserved glomerular filtration rate. Acute incubation of podocytes and KH-2 cells with elafibrinor or recombinant SIRT1, reversed the HFD-sera-induced oxidative stress, autophagy dysfunction, cell apoptosis, barrier marker loss, albumin endocytosis and re-uptake reduction.

Conclusions: Current study showed that elafibranor inhibited the progression of HFDinduced CKD through activation of renal PPARα, PPARδ, SIRT1, autophagy, reduction of oxidative stress and apoptosis in mice with steatohepatitis.

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2019 TDDW

P.0233

NS5A RESISTANCE-ASSOCIATED SUBSTITUTIONS ANALYSIS OF HCV VIRUS: PREVALENCE AND ITS ASSOCIATION WITH IL-28B POLYMORPHISM AND VIRAL LOAD Ta-Ya Lin1, Chung-Feng Huang1,3, Ming-Lun Yeh1,3, Ching-I Huang1, Chia-Yen Dai1,2,3, Meng-Hsuan Hsieh1,3, Shinn-Chern Chen1,3, Jee-Fu Huang1,2,3, Ming-Lung Yu1,2,3, Wan-Long Chuang1,2,3 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan3

C 型肝炎的 NS5A 抗藥相關變異：盛 行率以及與 IL28B 多型性和病毒量的 相關性 林大雅1 黃釧峰1,3 葉明倫1,3 黃駿逸1 戴嘉言1,2,3 謝孟軒1,3 陳信成1,3 黃志富1,2,3 余明隆1,2,3 莊萬龍1,2,3 高雄醫學大學附設醫院肝膽胰內科1 高雄醫學大學臨床醫學研究所2 高雄醫學大學醫學院內科學科3 Background: The NS5A resistance-associated substitutions (RASs) will affect the efficacy of NS5A inhibitors treatment in chronic hepatitis C patients. We evaluated the prevalence of several pre-treatment NS5A RASs in hepatitis C virus (HCV) genotype 1b cohort.

Aims: We aimed to analyze the connection of patient baseline characteristics, HCV viral load, IL28B variations, and NS5A RASs. Methods: We evaluated patients from 6 medical centers, total 359 patients with HCV genotype 1b infection. The NS5A RASs were detected by direct gene sequencing before directacting antivirals (DAAs) treatment. Patient baseline characteristics, viral load, and IL28B polymorphism were also analyzed.

Results: Overall, NS5A RASs were detected in 31.2% of patients. Among patients with HCV

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genotype 1b infection, 2%, 14.8% of patients had detected L31, Y93 mutations respectively. Patient with high HCV viral load (HCV RNA＞6000 KIU/ ml) was associated with L31 or Y93 mutation. In multivariate logistic regression analysis including high viral load, age and sex, IL28B-TT genotype was significantly associated with Y93 mutation.

HBV co-infection and interferon experienced did not affect the RAS significantly in our study group.

Conclusions: Pre-DAAs treatment NS5A RASs were present in 31.2% of patients. Among the RASs that may confer to resistance to current NS5A inhibitor, L31 and Y93 mutations had been detected in 2% and 14.8% of patients respectively.

Patient with high HCV viral load was associated with NS5A RASs. We also identified high viral load and genotype IL28B-TT as predictors for Y93 mutation in HCV genotype 1b patients.

2019 TDDW

P.024

INCIDENCE OF DIABETES MELLITUS AND LONG-TERM GLYCEMIC CONTROL IN PATIENTS WITH CHRONIC HEPATITIS C RECEIVING DIRECT-ACTING ANTIVIRAL THERAPY Wei-Fan Hsu1,2, Hsueh-Chou Lai1,3, Wen-Pang Su1, Cheng-Yuan Peng1,4, Guan-Tarn Huang1,4, Jaw-Town Lin5 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan2 School of Chinese Medicine, China Medical University, Taichung, Taiwan3 School of Medicine, China Medical University, Taichung, Taiwan4 Digestive Medicine Center, China Medical University Hospital, Taichung, Taiwan5

慢性 C 型肝炎患者接受直接作用抗病 毒藥物的糖尿病發生率與長期血糖控 制 許偉帆1,2 賴學洲1,3 蘇文邦1 彭成元1,4 黃冠棠1,4 林肇堂5 中國醫藥大學附設醫院消化系內科1 中國醫藥大學生物醫學研究所2 中國醫藥大學中醫系3 中國醫藥大學醫學系4 中國醫藥大學附設醫院消化醫學中心5 Background: Hepatitis C virus (HCV) increases the incidence of diabetes mellitus (DM). Recent evidence showed that CHC patients who achieved sustained virologic response (SVR) to HCV therapy had a lower risk for DM, and successful treatment of HCV in diabetic patients reduced the incidences of DM-related complications, including acute coronary syndrome, end-stage renal disease, and ischemic stroke. Direct-acting antiviral agents (DAAs) have been the standard of care for CHC, but the incidence of DM after DAA therapy and long-term glycemic control in these patients are still unknown.

Aims: To evaluate the incidence of DM before and after DAA therapy and dynamic changes in AC glucose, glycated hemoglobin (HbA1c), and

insulin resistance (IR) in CHC patients during and up to 15 months after DAA therapy.

Methods: From 2012 Sep to 2019 Apr, 718 CHC patients who had received a complete course of DAA therapy were enrolled in this retrospective study. Demographic and virological features, and on-treatment AC glucose, HbA1c, and IR values were recorded during and up to 15 months after DAA therapy.

Results: Of 718 patients, 312 (43.5%) patients were male, and 275 (38.3%) patients had liver cirrhosis. The median age was 62 (54–69) years (first quartile–third quartile). The median ALT was 63 (39–101) U/L. 524, 162, 4, 1, and 25 patients had genotype 1, 2, 3, 4, and 6 HCV infection, respectively, and 1 patient had mixed genotype (1a+2b) HCV infection (one patient lacked HCV GT data). 544 (75.8%), 153 (21.3%), and 21 (2.9%) patients had no DM (Group 1), DM before DAA therapy (Group 2), and DM after DAA therapy (Group 3), respectively. The median follow-up period after initiation of DAA therapy was 25.52 (18.57–39.48) months, and the incidence of DM after DAA therapy were 1.38% per year.

Group 2 had older age and lower albumin levels than Group 1. Groups 2 and 3 had higher AST, AC sugar, HbA1c, and IR levels, and proportions with IR＞2.5 than Group 1. Group 3 had higher ALT levels than Group 1. The median HbA1c in Group 1 increased from 5.5 (5.3–5.8) at baseline to 5.5 (5.1–5.8), 5.6 (5.4–5.8), 5.6 (5.4–5.9), 5.7 (5.4–5.9), and 5.6 (5.5–6.0)% at end of therapy (p＜0.001), 3 months after DAA therapy (P3M) (p＜0.001), P6M (p＜0.05), P12M (p＜0.01), and P15M (p＜0.001), respectively. The median HbA1c in Groups 2 (p=0.485) and 3 (p=0.788) did not significantly change from baseline until P15M. The median IR values in Groups 1 (p=0.471), 2 (p=0.921), and 3 (p=0.766) did not significantly change from baseline until P15M. Multivariate Cox regression analysis showed that HbA1c＞6% at baseline (13.550 (1.381–132.912), p=0.025) was the independent predictor of developing DM after DAA therapy.

Conclusions: The incidence of DM after DAA therapy was 1.38% per year, similar to that of the general population in Taiwan. DAA therapy mildly increased HbA1c in CHC patients without DM up to 15 months after DAA therapy and did not improve long-term glycemic control in CHC patients with DM.

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2019 TDDW

P.025

UTILITY OF THE MELD SCORE IN PREDICTING SHORT-TERM PROGNOSIS IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS Cheng-Chi Lee, Jen-Chieh Huang, Jeng-Shiann Shin Section of Gastroenterology and Hepatology, Cheng Ching General Hospital, Chung-Kang Branch, Taichung, Taiwan

MELD Score 於預測嚴重酒精性肝炎 病人短期預後的實用性 李政祺 黃仁杰 辛政憲 澄清綜合醫院中港分院胃腸肝膽科 Background: Alcoholic hepatitis is characterized by acute, or acute-on-chronic hepatic failure a n d a s s o c i a t e d w i t h a h i g h m o r t a l i t y. I t is a manifestation of alcoholic liver injury characterized by necrotizing inflammatory hepatic lesions and acute hepatic decompensation.

Increasing alcohol consumption has resulted in an increasing number of cases of alcoholic liver disease in Taiwan. According to previous reports, MELD is a useful clinical tool for gauging mortality and guiding treatment decisions in patient with alcoholic hepatitis, particularly those complicated by ascites and/or encephalopathy.

Aims: To investigate the utility of the MELD score in assessing short-term prognosis of patients with severe alcoholic hepatitis.

Methods: A retrospective study of 162 mortality patients with severe alcoholic hepatitis between Jan. 2006 and Dec. 2016 at the Cheng-Chin hospital Chung-Gang branch was performed.

After exclusion of 25 patients with incomplete data, they were classified as very high MELD score group (VH, No.53) and high MELD score group (H, No.84). Patients were evaluated on the basis of age, gender, laboratory data, symptoms and examinations. MELD scores for each patient were calculated according to the initial laboratory data during the admission. Data were statistically analyzed using the chi-squared test & student’s t-test. Analysis of survival was performed using the Kaplan-Meier method.

Results: Demographic data including average age, sexuality, complications and coexistence of malignancy of the VH and H groups was

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comparable. The severe alcoholic hepatitis with very high MELD score group (VH) was found to have higher leukocytosis, prolong of PT, higher total bilirubin, creatinine levels and hypoalbuminemia. The VH group prone to poorer prognosis than that of the H group but it was not significant.

Conclusions: Severe alcoholic hepatitis is associated with a high MELD score and high mortality in hospitalized patients. But the MELD score seems less useful in predicting short-term prognosis of severe alcoholic hepatitis patients.

2019 TDDW

P.026

HEPATITIS B AND C SCREENING ON SCREENING-NAÏVE ADULT RESIDENTS USING TWO QUANTITATIVE ANTIGENS Sheng-Nan Lu1, Wei-Cheng Huang2, Jia-Ling Tu1, Yu-Chen Lin3, Nain-Feng Chu3, Jing-Houng Wang4,5 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 Division of Geriatrics, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan2 Chiayi County Health Bureau, Chiayi, Taiwan3 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan4 Chang Gung University College of Medicine, Kaohsiung, Taiwan5

使用兩種 B 肝和 C 肝定量抗原做為未 經肝炎篩檢成人之篩檢工具 盧勝男1 黃偉城2 涂嘉玲1 林裕珍3 祝年豐3 王景弘4,5 嘉義長庚紀念醫院胃腸肝膽科1 嘉義長庚紀念醫院老年醫學科2 嘉義縣衛生局3 高雄長庚紀念醫院胃腸肝膽科4 長庚大學醫學院5 Background: Screening for hepatitis B and C is one of key events for elimination of viral hepatitis before 2025. Using best designs and tools may result in more reasonable outcomes, such as saving medical resources, decreasing unnecessary referral as well as achieving better cost-benefit. Our previous study showed the negative predictive value (NPV) was 100% for quantitative HBsAg (qHBsAg)＜8 IU/ml in prediction of HBVDNA＜2000 IU/ml, and both positive predictive value (PPV) and NPV were around 98% for HCV Ag in prediction of HCV viremia.

Aims: This abstract reports a community-based hepatitis B and C screening on screening-naïve adult residents in Chiayi county using qHBsAg and HCV Ag.

Methods: Population database was obtained from local Household Registration Offices in Chiayi county. Residents who experienced hepatitis B and C screenings by local primary care centers, the National Health Insurance Screening Program, non-government organizations (NGO), and the Chang Gung Memorial Hospitals were enrolled. Those who aged 30 years or younger were excluded. During Oct 2018 to May 2019, all Primary Health Care Centers of 17 townships, excluding Dapu, encouraged local candidates to undergo the screening.

Results: A total of 3983 residents was enrolled with mean age of 63.4 (SD: 14.1) years. Among them, 1612 (40.5%) were men. The prevalence of HBsAg and HCV Ag were 9.5% (n=379) and 4.0% (n=159), respectively. Among HBsAg-positive cases, 88 (23.2%) have qHBsAg less than 8 IU/ml. Till now, 90 (57.2%) out of 159 HCV Agpositive patients have already been referred for further management. There were 6 townships with higher HBsAg prevalence (10.0~21.2%) and 6 with higher prevalence of HCV Ag (5.4%~15.2%).

Among them, 3 townships were higher for both HBsAg and anti-HCV. These epidemiological findings were compatible with previous reports.

Conclusions: This screening provided a screening only to screening-naïve subjects.

The positive subjects we found almost met the treatment criteria. One step screening using two quantitative antigens was cost-benefit as our published report. The study not only detect candidates for anti-viral treatment, but also provide a reasonable screening model. This study also established local epidemiological information.

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P.027

PREVALENCE AND GENOTYPE DISTRIBUTION OF HEPATITIS C VIRUS INFECTION AMONG PRISONERS IN YUNLIN COUNTY Yu-Jen Fang1,2, Tsung-Hua Yang1,2, Shih-Jer Hsu1,2, Ji-Yuh Lee1,2, Min-Chin Chiu1,2, Chien-Hung Chen1,2,3 Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan1 Hepatobiliary Medical Center, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

雲林縣監獄受刑人 C 型肝炎病毒感染 率及基因型分佈 方佑仁1,2 楊宗樺1,2 徐士哲1,2 李基裕1,2 邱敏欽1,2 陳健弘1,2,3 國立臺灣大學醫學院附設醫院雲林分院內科1 國立臺灣大學醫學院附設醫院雲林分院肝膽醫學 中心2 國立臺灣大學醫學院附設醫院內科3 Background: The prisoners were a special population with high Hepatitis C virus (HCV) prevalence and variable access to healthcare. To reach the WHO goal of eliminating HCV before 2030, prisons should be listed as the priority places for micro-elimination.

Aims: To investigate the seroprevalence and genotype distribution of HCV among prisoners in Yunlin County.

Methods: All subjects in the Yulin Prison had been invited for screening of HBsAg and antiHCV. All anti-HCV positive subjects were called back to the clinic in Yunlin prison for further evaluation per requirements of National Health Insurance. Serum HCV RNA level was determined by Cobas® TaqMan® HCV Test v2.0 (Roche Molecular Diagnostics, CA, USA) with a lower limit of quantification (LLOQ) of 15 IU/mL; HCV genotype was determined by Cobas® HCV GT (Roche Molecular Diagnostics, CA, USA).

Advanced hepatic fibrosis (fibrosis stage F3) was assessed with fibrosis index based on 4 factors (FIB-4) test ≥3.25 or findings of ultrasonography.

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Results: A total 707 subjects in the Yulin Prison received hepatitis screening. The overall prevalence of positive anti HCV was 33.1% (234/707). The median age was 45.9 years. The overall HCV viremia rate was 69.2% (162/234).

The median log10 HCV RNA level at baseline was 6.46 (2.39-7.40). Twenty-seven patients (11.54%) were co-infected with hepatitis B. The genotype (GT) distribution was GT 6, 40.1% (65/162), GT 1a, 22.2% (36/162), GT 2, 11.7% (19/162), GT 3, 11.1% (18/162), and GT 1b, 10.5% (17/162) respectively. There were six patients had mixed type, such as GT3+6 (3), genotype 1b+2 (2), GT 1a+1b (1). Four (1.70%) and 3 (1.30%) patients had advanced hepatic fibrosis (F3) and compensated cirrhosis, respectively. Two patients had cancer, one for hepatocellular carcinoma and the other colon cancer with multiple liver metastases. Seventy-seven (32.9%) patients had elevation of alanine aminotransferase.

Conclusions: The prevalence HCV infection was high in Yunlin prison. The genotype distribution was quite different from the general population.

2019 TDDW

P.028

CORRELATION BETWEEN OXIDATIVE DAMAGE OF MITOCHONDRIA AND LIVER ENZYME CHANGE IN PATIENT WITH ACUTE HEPATITIS Pei-Yuan Su1, Yu-Chun Hsu1, Wei-Wen Su1, Chin-San Liu2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan1 Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua, Taiwan2

急性肝炎患者肝功能變化與粒線體氧 化壓力的關聯性

subjects was male. The etiologies of hepatitis included acute hepatitis A (5.6%), flare up of chronic hepatitis B (44.4%), drug induced liver injury (33.3%), alcohol hepatitis (11.1%) and sepsis (5.6%). The periods between pre- and post-treatment were 3 to 7 days. ΔCt of pretreatment had statistically negative correlation to ΔGPT/day. After gamma regression model adjusted by ΔCt and GPT of pre-treatment, HBV, cirrhosis and treatment duration, ΔCt of pretreatment was still significant negative correlation to ΔGPT/day.

Conclusions: The study showed lower oxidative stress before treatment was correlated to higher improvement of liver enzymes in patients with acute hepatitis. The result should be further investigated by large sample-size studies.

蘇培元1 徐友春1 蘇維文1 劉青山2 彰化基督教醫院胃腸肝膽科1 彰化基督教醫院血管基因體中心2 Background: Many studies had showed that mitochondria dysfunction was associated with many chronic liver diseases, such as alcoholic hepatitis, drug-associated liver diseases and hepatitis B and C infection. Little is known about the association between mitochondria and acute hepatitis.

Aims: We tried to compare mitochondria copy number and oxidative stress with clinical parameters from patients admitted due to acute hepatitis.

Methods: We included hospitalized patients at Changhua Christian Hospital because of acute hepatitis (defined as GPT＞200 U/L) from Nov. 2013 to Jan. 2018. All the patients received standard of care including glycyrrhizin therapy of acute hepatitis according to the etiology.

We compared the copy number and oxidative damage of mtDNA (ΔCt) from peripheral blood leukocytes with clinical parameters between two blood samples collected before and after treatments included anti-viral therapy or antibiotic therapy. The value of ΔCt was calculated as an index of oxidative stress to mtDNA. The primary endpoint was the change of GPT per day (ΔGPT/ day).

Results: 18 hospitalized patients were collected and the median GPT was 1045 U/L. The median age of subjects was 51 years and 55.6% of

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P.029

MUCINOUS CYSTIC NEOPLASM OF THE LIVER: A SINGLE CENTER EXPERIENCE IN TAIWAN Chia-Sheng Chu1, Cheng-Yuan Peng1, I-Ping Chang2, Wen-Hsin Huang1, Hsueh-Chou Lai1, Jaw-Town Lin1 Division of Hepatology and Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Department of Pathology, China Medical University Hospital, Taichung, Taiwan2

肝臟黏液性囊泡腫瘤—台灣中部醫學 中心的經驗 朱家聲1 彭成元1 江宜平2 黃文信1 賴學洲1 林肇堂1 中國醫藥大學附設醫院內科部消化系1 中國醫藥大學附設醫院病理部2 Background: Mucin-producing hepatic cystic neoplasms (MHCN), had been classified in to intrahepatic biliary cystadenoma and cystadenocarcinoma, comprising less than 5% of the liver cystic neoplasms. Since 2010, the advances in pathology, led MHCN into two different group: hepatic mucinous cystic neoplasm (MCN) and intraductal papillary neoplasm of bile duct (IPNB). MCN is cyst forming epithelial neoplasm composed of mucin producing epithelium and associated with ovarian-type subepithelial stroma. The clinical manifestation of MCN is non-specific and MCN is usually misdiagnosed as simple cyst in image study. Because MCN has as high as 15% risk of malignant transformation, the best therapeutic option is complete surgical resection.

However, the incorrect diagnosis always results in inadequate treatment in patients with MCN. Aims: The aim of our study is to present the clinical and radiologic findings of the patients with MCN. Methods: From 1994 to 2018, 25 patients with MHCN were documented in our hospital with pathologically proven. Only 17 patients was diagnosed as MCN. 16 patients with MCN without malignant transformation and one patient with MCN with focal adenocarcinoma in situ, which is also called invasive MCN (iMCN), were enrolled.

Results: There are only 2 males and 15 females.

The mean age at diagnosis was 57.1 (range 40

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to 75) years in MCN and the only one patient who had iMCN was been diagnosed at age 65.

Abdominal fullness (53%) is the most common symptom. The mean size of the tumors was 9.69 (range 0.5 to 30) cm of the MCN and the only iMCN was 21cm in diameter. The serum carbohydrate antigen 19-9 (CA199) level elevated in patient with iMCN (84 U/mL), but it also elevated in MCN group. 5 patients in MCN group had high CA199 (from 69.9 to 703 U/ mL), including one patient with hepatic failure due to acute hepatitis B virus reactivation and another one patient combined with hepatocellular carcinoma. Abdominal sonography found cystic mass with septum or solid portion in 82% of patients. 13 patients received lobectomy or partial hepatectomy and 2 patients underwent liver transplantation due to underlying liver cirrhosis and hepatic failure caused by acute hepatitis B virus reactivation. The mean follow-up duration in MCN group was 65.8 months. The patient with iMCN was followed for 62 months, but she was lost follow-up eventually.

Conclusions: MCN is a rare tumor that is usually incorrectly diagnosed. In Taiwan, MCN occur predominately in women. IPNB and MCN both belong to the MHCN group. IPNB presents with intrahepatic biliary duct dilatation which makes it easier being diagnosed in sonographic study. In contrast, MCN is usually incorrectly diagnosed as simple cyst in image studies. When we find an intrahepatic cystic lesion accompanied with internal septum or solid portion and no dilated intrahepatic biliary ducts, the MCN should be suspected. The best therapeutic choice is radical excision to prevent malignant transformation.

2019 TDDW

P.030

ETIOLOGY OF NON-B, NON-C HEPATOCELLULAR CARCINOMA: A COMMUNITY-BASED PROSPECTIVE STUDY Te-Sheng Chang1,2, Nien-Tzu Hsu3,4, Mei-Hsuan Lee5, Shu-Chuan Chen6, Yi Chen6, Sheng-Nan Lu1,2,3,4 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan3 Biostatistics and Bioinformatics Center of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan4 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan 5 Public Health Bureau, Tainan City Government, Tainan, Taiwan5 Public Health Bureau, Tainan City Government, Tainan, Taiwan6

非 B 非 C 型肝炎相關肝癌致病因子分 析：一社區性前瞻性研究 張德生1,2 許念慈3,4 李美璇5 陳淑娟6 陳怡6 盧勝男1,2,3,4 嘉義長庚紀念醫院肝膽胃腸科1 長庚大學醫學院2 高雄長庚紀念醫院肝膽胃腸科暨長庚大學醫學院 高雄分部3 高雄長庚紀念醫院生物統計暨生物資訊中心4 陽明大學臨床醫學中心5 台南市衛生局6

screenings.

Methods: During 2003 to 2013, around 370,000 residents were checked under a comprehensive health screening program in Tainan. Their health data was computerized and a serum bank was established. We linked the status of hepatitis B and C to the Health and Welfare Data Science Center, Ministry of Health and Welfare for overall mortality and cancer registration data.

Results: A total of 53,998 participants were available for analysis. Of them 43,854 were negative for HBsAg and anti-HCV. Compared to the 43,809 individuals without HCC, the 45 with HCC were older in age (64.2±10.6 vs. 56.9±10.0 year, p＜0.001), male predominant (68.9% vs.

42.3%, p＜0.001), had higher BMI (25.8±3.5 vs.

24.4±3.5 U/L, p=0.009), higher AST (37.0±27.5 vs. 24.9±11.8 U/L, p=0.005) and ALT (32.9±18.7 vs. 25.2±18.4 U/L, p=0.008), higher AFP＞20 (p ＜0.001), higher creatinine (1.3±1.4vs. 1.1±0.3 mg/dL, p＜0.001), higher uric acid (6.3±1.6 vs.

5.7±1.6 mg/dL, p=0.023), lower total cholesterol (199.4±44.7 vs. 211.2±38.2 mg/dL, p=0.038), and triglyceride (110.9±54.1 vs. 132.4±99.0 mg/dL, p=0.011), lower platelet (194.9±70.4 vs.

233.6±60.7 uL, p＜0.001), higher FIB4 score (2.6±2.1 vs. 1.4±0.7, p＜0.001) and blood sugar (113.0±32.4 vs. 96.9±29.8 mg/dL, p＜ 0.001). Cox regression analysis revealed that age [HR=1.06 (1.02, 1.10), p=0.003], sex [HR=2.39 (1.17, 4.88), p=0.017], AST [HR=6.59 (2.81, 15.44), p＜0.001], triglyceride [HR=0.23 (0.08, 0.67), p=0.007], AFP [227.13 (67.12, 768.59), p ＜0.001], FIB4 score [1.26 (1.15, 1.38), p＜0.001] and sugar [1.009 (1.003, 1.015), p=0.005] were independent risk factors.

Conclusions: This study provided insights into the HCC risk factors other than viral hepatitis in the community adults.

Background: In addition to viral hepatitis and cirrhosis, some metabolic, environmental and genetic factors were also linked to hepatocellular carcinoma (HCC).

Aims: We prospectively analyzed risk factors of HCC in a large cohort of non-B, non-C adults aged＞40 receiving comprehensive community

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2019 TDDW

P.031

KINETICS IN SPLEEN STIFFNESS VALUES THROUGH ELASTOGRAPHY IN PATIENTS WITH CHRONIC HEPATITIS C ON AND OFF TREATMENTS WITH DIRECT-ACTING ANTIVIRALS Sheng-Hung Chen1,2,3, Cheng-Yuan Peng2,3, Hsueh-Chou Lai2,4, Wei-Fan Hsu2, Guan-Tarn Huang2,3, Jaw-Town Lin2,3 Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 College of Chinese Medicine, China Medical University, Taichung, Taiwan4

接受 Direct-Acting Antivirals 治療之 慢性 C 型肝炎病患治療中及治療後脾 臟硬度值變化之相關因子 陳昇弘1,2,3 彭成元2,3 賴學洲2,4 許偉帆2 黃冠棠2,3 林肇堂2,3 中國醫藥大學臨床醫學研究所1 中國醫藥大學附設醫院內科部消化系2 中國醫藥大學醫學系3 中國醫藥大學中醫學系4 Background: Reports on spleen stiffness (SS) kinetics through acoustic radiation force impulse (ARFI) elastography in patients receiving directacting antiviral (DAA) therapy are limited.

Aims: This prospective study aimed to demonstrate the serial changes of SS and liver stiffness (LS) values and to identify the independent factors that explain the SS and LS and their declines at baseline and follow-up visits.

Methods: Consecutive patients with chronic hepatitis C (CHC) underwent baseline concomitant LS and SS measurement and serial LS and SS measurements at baseline, ontreatment Week 4, end of treatment (EOT), 12 weeks post-EOT (sustained virological response), and 24, 36, 48, 60 and 84 weeks post-EOT through ARFI. Univariate and multiple linear models using generalized estimating equations

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were implemented to estimate the covariate estimates, standard errors (SE) and significance correlating with all the acquired measurement values and changes (declines) (baseline minus follow-up values).

Results: A total of 277 patients received at least one session of LS and SS measurements including the baseline. The median age was 63 years. At treatment baseline, Week 4, EOT and 12 weeks post-EOT, the serial median SS values were 2.86 (95% confidence interval: 2.35, 3.37), 2.81(2.42, 3.45), 2.96 (2.61, 3.51), 2.91(2.41, 3.68) (n=65, P=0.751); serial LS values were 1.87 (1.23, 2.28), 1.54 (1.20, 2.12), 1.53 (1.17, 2.02), 1.40 (1.12, 1.88) (n=193, P＜0.001).

Baseline SS values (estimate=0.590, SE=0.0510, P＜0.001) and platelet count (-0.002, 0.0006, P=0.003) independently explained the serial SS values (total n=866) adjusting for other baseline covariates. Moreover, baseline SS values (0.566, 0.0590, P＜0.001), baseline LS values (-0.936, 0.0607, P＜0.001), and platelet count (-0.001, 0.0006, P=0.010) explained the SS declines (n=589). By contrast, time intervals (months) (-0.027, 0.0034, P＜0.001), baseline LS values (0.684, 0.0314, P＜0.001), and international normalized ratio (INR) (1.197, 0.2238, P＜0.001) independently explained the serial LS values (total n=1239). Time intervals (0.019, 0.0036, P ＜0.001), baseline LS values (0.406, 0.0395, P ＜0.001), and INR (-1.536, 0.2851, P＜0.001) explained the LS declines (n=962).

Conclusions: SS values did not change significantly on or up to 12 weeks off DAA therapy in CHC patients. Baseline SS values positively correlated with both the serial SS values and declines over time. Baseline LS values and platelet count negatively correlated with the SS declines.

2019 TDDW

P.032

IMPROVEMENT OF HYPERURICEMIA IN CHRONIC HEPATITIS C PATIENTS RECEIVING DIRECTLY ACTING ANTIVIRAL AGENTS Tyng-Yuan Jang1,2, Ching-I Huang1, Ming-Lun Yeh1,3, Po-Cheng Liang1, Chung-Feng Huang1,3, Ming-Lung Yu1,3 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Department of Internal Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan2 Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan3

慢性 C 型肝炎接受 DAA 治療後高尿酸 將改善

levels (5.6±1.5 mg/dL vs 6.0±1.7 mg/dL, respectively; P＜0.001). The proportion of hyperuricemia incidences significantly decreased after treatment (25.8% vs 35.7%, respectively; P=0.001). The improvement was only observed in patients with a fibrosis-4 index (FIB-4)＜6.5 (25.7% vs 37.1%, P=0.001) but not in those patients with a FIB-4 ≧ 6.5 (26.3% vs 28.9%, P=1.00). A multivariate analysis revealed that the factor that was associated with significantly decreased SUA levels was FIB-4＜6.5 (odds ratio [OR]/95% confidence intervals [CI]: 3.22/1.049.95, P=0.04) and estimated glomerular filtration rate (eGFR)＜60 ml/min/1.73m 2 ([OR]/[CI]: 4.34/1.94-9.73, P＜0.001). There existed a trend of a higher proportion of patients with significant SUA improvement along with the decrement of FIB-4 (29.7%, 25% and 10.5% in patients with FIB-4＜3.25, 3.25-6.5 and＞6.5, respectively, trend P=0.03).

Conclusions: SUA levels were significantly decreased in CHC patients after viral eradication.

The improvement was particularly enhanced in patients with mild liver disease.

張庭遠1,2 黃駿逸1 葉明倫1,3 梁博程1 黃釧峰1,3 余明隆1,3 高雄醫大學附設醫院肝膽胰內科1 屏東醫院2 高雄醫大學附設醫院肝炎研究中心3 Background: Hepatitis C virus (HCV) eradication via the use of antivirals ameliorates metabolic profiles. The changes in serum uric acid (SUA) levels in chronic hepatitis C (CHC) patients who receive antivirals are not well understood.

Aims: We aimed to address this issue by comparing the SUA changes before and after the achievement of a sustained virological response (SVR, which is defined as HCV RNA seronegativity at 12 weeks after the end of treatment).

Methods: Two hundred and thirteen SVR patients who were treated by directly acting antivirals (DAAs) were consecutively enrolled. Pre- and posttreatment SUA levels were compared.

Hyperuricemia was defined as a uric acid level＞ 7.0 mg/dL in men and＞6.0 mg/dL in women.

Results: The SUA levels significantly decreased after treatment, as compared to the pretreatment

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2019 TDDW

P.033

HBEAG LOSS INCIDENCE RATE DECLINE SHARPLY AFTER FIRST YEAR NUCLEOS(T)IDE ANALOGUE THERAPY IN HBEAG POSITIVE CHRONIC HEPATITIS B PATIENTS Chien-Wei Peng1,2, Wen-Juei Jeng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Chang Gung University, College of Medicine, Taoyuan, Taiwan2 Liver research unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan3

e 抗原陽性之慢性 B 型肝炎患者接受 核苷酸類抗病毒藥物一年後 e 抗原轉 陰之發生率大幅下降 彭建維1,2 鄭文睿1,2 簡榮南1,2,3 廖運範2,3 林口長庚紀念醫院胃腸肝膽科1 長庚大學醫學院2 林口長庚紀念醫院肝臟研究中心3 Background: Higher pretreatment alanine transferase (ALT) and alpha-fetoprotein level (AFP) correlated with higher HBeAg loss rate during nucleos(t)ide analogue (Nuc) therapy.

However, it is unclear whether the impact of baseline ALT and AFP level is limited to early phase or constant along the treatment course.

Aims: This study aimed to investigate the respective incidence of HBeAg loss during each year of Nuc treatment.

Methods: The study included 320 courses of Nuc therapy in 293 HBeAg positive patients and 27 patients with HBeAg reversion who had proper measurement of AFP level during the beginning of treatment. Baseline age, gender, cirrhosis, ALT, genotype, HBsAg and HBV DNA levels were analyzed. Serum HBV DNA was measured by Cobas Amplicor HBV Monitor (Roche Diagnostics, negative＜20 IU/ml), HBsAg was measured using Roche Elecsys II kit (negative＜0.05 IU/ml). The HBeAg loss incidence rate at each respective year was calculated by number of new HBeAg loss per patient-at-risk in each year.

Results: The median age was 44.3-year-old, 72.2% were males, 55.9% were genotype B,

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44.1% were genotype C infected and 24.7% had evidence of cirrhosis. Of the 320, 208 (65%) courses showed HBeAg loss at a median time of 50.3 (1.9-454.1) weeks of therapy (5-year: 67.6%). The 5-year cumulative HBeAg loss rate was higher in patients with hepatitis flare (AE) than without (76.2% vs. 44.9%, Log rank test, P ＜0.001). In patients with AE, the HBeAg loss incidence rate (per 100 person-year) was highest in the 1st year: 53.7, turned half in the 2nd year, and 16.5 in 4th year. The HBeAg loss rate was lower (1st year: 18.5), gradually decreased in patients without AE (Figure 1A). The HBeAg loss incidence rate in 1st year showed dose dependent manner with higher ALT and AFP but was similar among each group during follow-up duration (Figure 1B).

Conclusions: HBeAg loss occurred majorly during the 1st year on Nuc therapy. The 1st year HBeAg loss rate was higher in patients with higher ALT and AFP levels, and lowest in patients with ALT＜5X ULN. These results suggest that the impact on HBeAg loss by endogenous host immune response, no matter how strong, is declining after 1st year of therapy and HBeAg loss afterward is mainly the effect of Nc therapy.

It remains to explore whether add-on IFN-based therapy in those remained HBeAg positive at end of 1st year of Nuc therapy may achieve better response.

2019 TDDW

P.034

THE EFFICACY AND SAFETY OF 12WEEK LEDIPASVIR/SOFOSBUVIR TREATMENT IN TAIWAN GT2 & GT6 HCV PATIENTS: REAL-WORLD DATA FROM TAIWAN CMH-LY HOSPITAL Pei-Lun Lee, Jyh-Jou Chen, Hung-Da Tung, Chun-Ta Cheng, Tang-Wei Chuang Chi Mei Hospital, Liouying, Tainan, Taiwan

針對 C 型肝炎基因型 2 及基因型 6 使 用 12 週 Ledipasvir/Sofosbuvir 治療 的療效和安全性評估：來自台灣的真 實數據

treatment experienced, and 70 patients were liver cirrhotic. The overall SVR12 was 96.8% (Per protocol). During the treatment, the percentage of early discontinuation was 1 % for GT2 and 1.55 % for GT6 HCV patients. For the eGFR alteration of patients during 12-week LDV/SOF treatment, there was no significant alteration from baseline to SVR12, regardless of baseline eGFR value＜ 60 ml/min/1.73m2 or＞60 ml/min/1.73m2.

Conclusions: In Taiwan real world, 12-week LDV/SOF±RBV treatment achieved high SVR12 in GT6 patients, and the efficacy is comparable to pivotal clinical studies. From our current evidences, 12-week LDV/SOF in GT2 HCV patients is efficacious and safe, and more data will be further reported.

李佩倫 陳志州 董宏達 鄭俊達 莊棠惟 奇美醫療財團法人柳營奇美醫院 Background: 12-week Ledipasvir/Sofosbuvir (LDV/SOF) has been approved for the treatment in HCV-2 patients in Taiwan, Korea, and Japan based on the results from 3 clinical studies.

However, the real-world evidences of LDV/SOF in GT2 HCV patients are limited around the world. In addition, although clinical study and several realworld publications havedemonstrated the efficacy and safety of LDV/SOF in GT6 HCV patients, in Taiwan, thedata is still rare in real world.

Aims: In this study, we aim to investigate the real-world efficacyand safety of 12-week LDV/ SOF treatment in GT2 and GT6 HCV patients by analyzingthe data from Taiwan CMH-LY hospital.

Methods: Clinical data of GT2 and GT6 HCV patients receiving 12-week LDV/SOF±RBV during 2018 and 2019 in CMH-LY hospital were collected and retrospectively analyzed. Primary endpoint: Undetectable HCV RNA at 12 weeks post treatment (SVR12).

Results: There are around 200 HCV-2 and 193 HCV-6 patients receiving 12-week LDV/ SOF±RBV during 2018 and 2019 in Taiwan C M H - LY. A m o n g 2 0 0 G T 2 p a t i e n t s , 7 3 patients were men, 16 patients were treatment experienced, and 31 patients were liver cirrhotic.

3of them already completed follow-up duration, and all of them achieved SVR12. Theother patients will have SVR12 results around September and will be reported. For 193 GT6 patients, 84 patients were men, 11 patients were

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P.035

REAL WORLD EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR AND LEDIPASVIR/SOFOSBUVIR AGAINST MIXED GENOTYPE HEPATITIS C INFECTION: INTERIM RESULTS OF A MULTICENTER POOLED ANALYSIS IN TAIWAN Wen-Nan Chiu1, Chao-Hung Hung2,3, Sheng-Nan Lu2,3, Mei-Yen Chen4, Shui-Yi Tung2, Chien-Hung Chen5, Tsung-Hui Hu5, Wei-Ming Chen2,3, Jin-Hung Hu1, Te-Sheng Chang1,2,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan1 ivision of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan2 College of Medicine, Chang Gung University, Taoyuan, Taiwan3 Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan5

以 Glecaprevir/Pibrentasvir 或 ledipasvir/Sofosbuvir 治療混合基因 型 C 型肝炎真實世界療效：一台灣多 中心混合期中分析 邱文南1 洪肇宏2,3 盧勝男2,3 陳美燕4 董水義2 陳建宏5 胡琮輝5 陳慰明2,3 胡錦鴻1 張德生1,2,3 雲林長庚紀念醫院肝膽胃腸科1 嘉義長庚紀念醫院肝膽胃腸科2 長庚大學醫學院3 長庚科技大學護理學院4 高雄長庚紀念醫院肝膽胃腸科5 Background: The response rates of current direct-acting antiviral agents (DAAs) for chronic hepatitis C virus (HCV) infections with genotype 1 to 6 are excellent. However, the data of DAA treatment for mixed genotype infections are sparse.

Aims: Here, we report the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB)

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and ledipasvir/sofosbuvir (LDV/SOF) for mixed genotype HCV infections in a real-world setting in Taiwan.

Methods: All consecutive HCV patients with mixed genotype infections in three Chang Gung Memorial hospitals in southern Taiwan (Yunlin, Chiayi, and Kaohsiung) treated with pangenotypic DAAs LDV/SOF (except for genotype 3) or GLE/PIB were analyzed. The primary treatment outcomes were aviremia at the end of treatment (ETR) and sustained virologic response 12 weeks after cessation of treatment (SVR12).

The adverse events (AE) were also evaluated.

Results: A total of 117 HCV patients receiving DAA had mixed infection of any 2 or 3 genotypes of 1a, 1b, 2, 3, or 6 in these 3 hospitals from Jan 2017 to May 2019. Of them 54 received GLE/ PIB and 63 received LDV/SOF. After excluding 12 patients not yet completing DAA therapy, all the remaining 105 (100%) patients achieved ETR. Among the 47 patients reaching 12 weeks after cessation of treatment, 46 (97.9%) achieved SVR12. Only one genotype Ib+6 patient in the LDV/SOF group did not achieved SVR12. The ETR and SVR12 were not different between the 2 groups of GLE/PIB and LDV/SOF. One patient suffered liver decompensation from Child A to Child B and was lost to follow-up after GLE/ PIB therapy for 4 weeks. Another one patients with decompensated cirrhosis died after LDV/ SOF+ribavirin therapy for 3 weeks. The common AEs for GLE/PIB vs. LDV/SOF included pruritus (6.8 vs. 2.6%), fatigue (2.6 vs. 3.4%), decreased appetite (0 vs. 4.3%), abdominal pain (4.3 vs.

2.6%) and hyperbilirubinemia (1.7 vs. 0.8%). One patient receiving ribavirin in the LDV/SOF group had a hemoglobin level drop to 6.7 g/dL. Conclusions: Both GLE/PIB and LDV/SOF were well tolerated and achieved high response rates in mixed genotype HCV patients in the real world setting.

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P.036

THE EFFECTS OF SUSTAINED VIROLOGICAL RESPONSE ON GLYCEMIC CONTROL IN TYPE 2 DIABETIC PATIENTS WITH CHRONIC HEPATITIS C Ching-Chu Lo1, Shih-Che Hua2, I-Wen Hung1, Jui Fang Huang1, Kuo-Chih Huang1, Mei-Tsu Chen1 Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan1 Division of Endocrinology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan2

statistically associated with HbA1c reduction (P＜ 0.001). Among the T2D with baseline HbA1c＞7% (N=64), SVR was strongly associated with HbA1c changes (P＜0.001), however, baseline Hba1c ≦7% (N=71), SVR not statistically associated (P=0.408).

Conclusions: DAA-based eradication of HCV resulting in SVR did improve glycemic control.

Our study results showed the effects of glycemic improvement is more prominent in poorer blood sugar control group (defined as HbA1c＞7%) before receiving DAA. It implies that DAA therapy is more urgently needed for those with poorer blood sugar control for T2D patients with HCV infection.

治療慢性 C 型肝炎達到持續病毒學反 應有助於第二型糖尿病之血糖控制 羅清池1 花士哲2 洪憶雯1 黃瑞芳1 黃國智1 陳美足1 天主教聖馬爾定醫院內科部胃腸肝膽科1 天主教聖馬爾定醫院內科部新陳代謝科2 Background: Currently, direct-acting antiviral drugs (DAA) are the gold standard for treating Chronic hepatitis c (HCV) infection, while yielding sustained virological response (SVR) in nearly all patients. HCV infection directly impairs glucose metabolism and contributes to insulin resistance.

Among patients with both type 2 diabetes (T2D) and HCV infection, SVR achieved by DAA therapy may improve glycemic control, but the available studies are limited.

Aims: To examine the effects of SVR achieved by DAA therapy on glycemic control, as measured by glycated hemoglobulin (HbA1c) in T2D patients with HCV infection.

Methods: We conducted a retrospective cohort study of T2D patients from Saint De Porres Hospital who had a positive HCV RNA test and received first course of DAA between 25 Jun, 2017 and 22 Jan, 2019. The effects of SVR on changes of HbA1c was statistically evaluated by Wilcoxon rank sign test (SPSS version 24.0).

Results: A total of 135 patients T2D patients with HCV treated by DAA were enrolled and all achieved SVR (100%). Of 135 patients, mean age was 67.1 years-old and male was 54.2%.

Before DAA therapy, mean viral load of HCV was 3858690.74. All patients achieved SVR (post-DAA therapy HCV RNA non-detectable). SVR was

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P.037

HEPATITIS C VIRUS RE-INFECTION JUST AFTER FINISHING DIRECTACTING ANTIVIRAL AGENT (D.A.A.) TREATMENT Chih-Wei Yen, Yung-Yu Hsieh, Wei-Lin Tong, Chein-Heng Shen, Chao-Hung Hung, Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang GungMemorial Hospital, Chiayi, Taiwan

口服 C 型肝炎藥物治療結束後短期內 是否會再次感染 C 型肝炎病毒 顏志維 謝詠諭 童威霖 沈建亨 洪肇宏 盧勝男 長庚醫療財團法人嘉義長庚紀念醫院內科部胃腸 肝膽科 Background: In Taiwan, most of the liver cirrhosis and liver cancer are caused by viral hepatitis, while chronic viral hepatitis includes hepatitis B and hepatitis C. The prevalence of hepatitis B has been greatly reduced after the vaccine is popularized. In epidemiological studies, more than 50% of the hepatitis C epidemic areas in southern Taiwan, there is no effective HCV vaccine, and the treatment of interferon in the past is not effectively eliminate hepatitis C. Fortunately, in the past five years, the development of oral direct anti-viral drugs has been able to achieve more than ninety percent sustained viral response. Therefore, the core strategy of hepatitis C developed by public health scholars has first led the prevention with treatment.

Aims: We had known one of most reason of treatment failure with peg-interferon/ribavirin (PR) is viral re-infection. But, there was no analysis about how soon patient is possibly get re-infection during and post treatment. In the era of D.A.A., which have very high sustained viral response rate, this issue is worth to be paid attention because it may press us to survey where is the pathogen from to avoid risk of treatment failure.

Methods: In more than twelve-hundred treatment experience, we had thirty-six treatment failure cases. Two of them are considered causing by viral re-infection because of different viral genotype from before and after treatment. We report the two cases. This is a 83 y/o, treatment

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naive, compensated cirrhotic man. He had completed Glecaprevir–Pibrentasvir (Mavyret) standard dose treatment since 08/22/2018. His virus genotype is 1b and pre-treatment viral load is 6.72 Log IU/mL. He had normalized liver enzyme and end of treatment response (ETR).

However, one month after end of treatment, he had different type (genotype 2) viremia and abnormal liver enzyme. Another is 54 y/o, PR treatment failure for three times (one-year, sixmonths, six-months- treatment course) man. His virus genotype is 1b and pre-treatment viral load is 6.16 Log IU/mL. He was documented have advanced fibrosis (F4) in Acoustic Radiation Force Impulse (ARFI) scan before D.A.A. treatment. He had completed Daclatasvir–Asunaprevir standard dose treatment since 02/10/2017 for six months.

He had sustained viral response (SVR). However, he was found HCV viremia again on 01/28/2019.

And his viral load is 6.65 Log IU/mL and genotype is 2.

Results: We found patient may get re-infection even just one month post D.A.A. treatment.

These two patients both more than 50 year old male. They all had advanced fibrotic liver and pretreatment viral load were＞6 Log IU/mL. And, the pre-treatment genotype is 1b and get re-infection with genotype 2.

Conclusions: We should take more care about the issue of re-infection post D.A.A. treatment not only the high treatment costs but also the treatment-lead-prevention strategy. We now know there may be no immune response generated after D.A.A. treatment to prevent re-infection.

This finding press us to find out the origin of the pathogen. Also, we should consider sequencing all treatment failure virus besides the two to identified if there is other re-infection case.

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P.038

P.039

Hung-Chih Chiu, Shih-Chieh Chien, Ting-Tsung Chang, Chiung-Yu Chen, Pin-Nan Cheng

Yu-Ting Lai, Wen-Chieh Huang, Ming-Jen Sheu, Chi-Shu Sun, Poh-Poo Lim, Hsing-Tao Kuo

REAL-WORLD RESULT OF SOFOSBUVIR/LEDIPASVIR FOR GENOTYPE 2 CHRONIC HEPATITIS C TREATMENT

ULTRASONOGRAPHIC SURVEILLANCE OF HEPATOCELLULAR CARCINOMA IN CIRRHOSIS: COMPARE 3- AND 6-MONTH INTERVAL

Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

夏奉寧對第二型慢性 C 型肝炎於真實 世界中之治療成果

比較肝硬化的病人中，以每三個月及 六個月超音波的篩檢預後有無差異

邱宏智 簡世杰 張定宗 陳炯瑜 鄭斌男

賴祐廷 黃文杰 許銘仁 孫啟書 林寶寶 郭行道

國立成功大學醫學院附設醫院內科部

奇美醫療財團法人奇美醫院永康院區

Background: Sofosbuvir/Ledipasvir is standard treatment for genotype 1, 4, 5, 6 hepatitis C infection treatment worldwide. Integrate analysis of clinical trial in Taiwan, Japan and New Zealand showed sustained virologic response rate around 96%. However, there was scanty real-world data about genotype 2 treatment by sofosbuvir/ ledipasvir.

Aims: To evaluate virological response of hepatitis C genotype 2 infection treated by sofosbuvir/ledipasvir.

Methods: We enrolled patients with chronic hepatitis C genotype 2 infection from National Cheng Kung University hospital (NCKUH) and Tainan hospital. All patients received sofosbuvir/ ledipasvir reimbursed by national health institute.

HCV RNA was checked at baseline, end of treatment and 12 weeks after cessation of therapy (SVR12).

Results: Total 573 patients with genotype 2 infection treated with sofosbuvir/ledipasvir for 12 weeks. The average age was 61.4-yearold and 38.0% of patients were male. Medium FIB-4 was 1.81 (0.12-27.36) and FIB-4 ≥ 3.25 in 16.8% patients. Medium baseline HCV RNA was 1570000 IU/L (65-108). HCV RNA at end of treatment was available in 65.3% (374/573) patients. Of them, 99.2% (371/374) HCV RNA was undetectable. Only eight SVR12 data was available, and one patient had positive HCV RNA. Conclusions: Sofosbuvir/ledipasvir had good viral suppression to genotype 2 infection during the treatment and the result of SVR12 was pending.

Background: Hepatocellular carcinoma (HCC) surveillance with abdominal ultrasonography (US) for patients with chronic hepatitis B or chronic hepatitis C was recommended by current guidelines. The 2018 AASLD guideline recommends US surveillance with or without AFP every 6 months for high risk groups. In Taiwan, the common practice regarding US surveillance intervals were every 3-6 month in cirrhotic patients and 6-12 month in other chronic liver disease patients. However, the prognosis with more intense interval of surveillance US (3 month) also has not been well evaluated for Taiwanese with cirrhosis which is the most important risk factor of HCC. Aims: Evaluate outcomes of HCC diagnosed during surveillance using US with different interval (every 3 month and every 6 month). We also evaluate if the outcome of HCC diagnosed with more intense surveillance interval every 3 month for patients with cirrhosis related to Chronic hepatitis B and/or Chronic hepatitis C. Methods: During 2011–2016, 90 patients underwent US surveillance were diagnosed with HCC and divided into 4 groups according to the patterns of diagnosis: (A) immediate diagnosis by recall procedure within 3 month (N=43, 47.8%) after positive US, (B) enhanced follow-up: (N=23, 25.6%) the initial recall procedures were negative and the diagnosis was made later through repeated workup during follow-up, (C) late call back: (N=14, 15.6%) the US had revealed new ≧ 1 cm nodule(s) but the recall procedures

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were deferred for＞3 months, and (D) beyond ultrasonography: (N=10, 11.1%) the diagnosis of HCC was made purely by any recall procedure triggered by elevation of alpha-fetoprotein or other reason, and prior US surveillance had been negative. Firstly, we excluded group D because the positive recall procedures was not attributed to surveillance US but the other causes, especially increased AFP level. Then, we evaluated the association between prognosis and US surveillance interval with 3 month (1-4 month) and 6 month (4-8 month). We evaluated the prognosis of subgroup that only including cirrhotic patients underwent different surveillance interval of US (3 m versus 6 m).

Results: The baseline characteristics, including age, gender, etiology of hepatitis, prevalence of liver cirrhosis, Child-Pugh score, BCLC stages, tumor number and sive or US surveillance intervals among Group A-D were not different.

After exluding Group D, patients were re-classified to curative stage (BCLC stage 0 and A) and noncurative stage (BCLC stage B and C). Among both group, there were no significant association between US surveillance intervals with 3 month and 6 month (p=0.789). Within cirrhotic patients divided to curative stage and non-curative group, there was also no significant association between 3 month and 6 month surveillance interval (p=0.666), but the 3-year survival rate was significant better within patients underwent 3 month US surveillance interval (p=0.030).

Conclusions: US surveillance follow-up by current guidelines which recommend surveillance interval every 6 month is compatible with our study within cirrhotis and non-cirrhotic patients, because there was no significance statistics between curative stage and surveillance interval longer than 3 months. However, among cirrhotic patients, more intense US surveillance interval every 3 month is not beneficial for the outcomes.

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P.040

A COMPREHENSIVE PEOPLECENTERED OUTREACH HEALTHCARE SYSTEM TARGETING HCV MICRO-ELIMINATION IN HYPERENDEMIC AREAS OF TAIWAN (COMPACT) – ESTABLISHMENT OF A MODEL TOWARD HCV ELIMINATION: INTERIM REPORT Ching-I Huang1,2, Po-Cheng Liang1, Yu-Ju Wei1, Po-Yao Hsu1, Chang-Ting Hsu1, Ming-Lun Yeh1,2, Chung-Feng Huang1,2, Jee-Fu Huang1,2, Chia-Yen Dai1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan2

以人為本的全面外展篩檢系統，針對 台灣高盛行地區的 C 型肝炎微量消除 （COMPACT）—建立消除 C 型肝炎的 模式 黃駿逸1,2 梁博程1 魏鈺儒1 許柏堯1 徐成鼎1 葉明倫1,2 黃釧峰1,2 黃志富1,2 戴嘉言1,2 莊萬龍1,2 余明隆1,2 高雄醫大學附設醫院肝膽胰內科1 高雄醫大學醫學院2 Background: Taiwan National Health Insurance started reimbursement of direct-antiviral-agents (DAA) for hepatitis C virus (HCV) in 2017.

However, national HCV elimination is daunting because of barriers in awareness and linkage-tocare.

Aims: We establish a model of outreach healthcare system in HCV hyperendemic (＞25%) villages in Taiwan and evaluate the effective in increasing rates of HCV diagnosis, accessibility and linkage-to-care rates.

Methods: The program by an “outreach HCVcheckpoint team” and an “outreach HCV-

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eliminating team” is implemented in Chidong/ Chikan from January 2019. The first round screen, based on “door-by-door” strategy, include questionnaires, liver enzymes, hepatitis markers, HCV RNA/genotyping. HCV viremic subjects are linked to outreach HCV-eliminating team subsequently. The second round screen for antiHCV-positive subjects will be executed in 2020.

Results: By May 2019, 315 (28%) of 1113 screened subjects are anti-HCV-positive.

Among 315 anti-HCV-positive subjects (mean age, 63y), 185 (58.7%) are male; 134 (42.5%) had HCV viremia. HCV GT1b was the most prevalent genotype (55.2%), followed by HCV GT2 (38.6%). At enrollment, only 186 (59%) antiHCV-positive subjects had HCV awareness; 152 of 186 (81.7%) had accessed HCV disease; 75 (49.3% of accessed subjects, 40.3% of aware subjects and 23.8% of anti-HCV-positive subjects) had received antivirals. Of 75 subjects who ever received anti-HCV therapy, 45 (88.2%) of 51 subjects experienced to IFN-based therapy, 20 (100%) of 20 subjects experienced to IFN-free DAA therapy and 4 (100%) of 4 subjects who experienced to both IFN-containing and IFNfree DAA regimens are HCV RNA negative at enrollment. Of 134 HCV-viremic subjects, 70 are successfully linked to outreach care team and start DAA therapy.

Conclusions: There remain huge gaps in each HCV care cascade step among HCV patients in a hyper endemic area. Comprehensive outreach screening and treatment programs are highly effective and necessary to overcome the hurdle toward HCV micro-elimination.

P.041

COMORBIDITIES AND OUTCOME OF ALCOHOLIC AND NONALCOHOLIC LIVER CIRRHOSIS IN TAIWAN – A POPULATION-BASED STUDY Tzu-Wei Yang1,3,4, Ming-Chang Tsai1,2,3, Chi-Chih Wang1,2,3, Yao-Tung Wang3,6, Wen-Wei Sung2,3, Ming-Hseng Tseng5, Chun-Che Lin1,2,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan2 School of Medicine, Chung Shan Medical University, Taichung, Taiwan3 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan4 Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan5 Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan6

台灣酒精性與非酒精性肝硬化之共病 與癒後分析 楊子緯1,3,4 蔡明璋1,2,3 汪奇志1,2,3 王耀東3,6 宋文緯2,3 曾明性5 林俊哲1,2,3 中山醫學大學附設醫院內科部肝膽腸胃內科1 中山醫學大學醫學研究所2 中山醫學大學醫學系3 交通大學生物科技系暨研究所4 中山醫學大學醫學資訊學系5 中山醫學大學附設醫院內科部胸腔內科6 Background: The prognosis of different etiologies of liver cirrhosis (LC) is not well understood.

Previous reports performed on alcoholic LCdominated cohorts have demonstrated few, conflicting results.

Aims: We aimed to compare the outcome and the effect of comorbidities on survival rates between alcoholic and non-alcoholic LC patients in a viral hepatitis-dominated LC cohort.

Methods: Using the Longitudinal Health Insurance Database, we identified newly

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diagnosed alcoholic and non-alcoholic LC patients, age ≥ 40 years old, between 2006 and 2011. The hazard ratios (HRs) were calculated using the Cox proportional hazard model and the Kaplan-Meier method.

Results: A total of 472 alcoholic LC and 4,313 non-alcoholic LC patients were identified in our study cohort. We found that alcoholic LC patients were predominantly male (94.7%) and younger (78.8% of alcoholic LC and 37.4% of nonalcoholic LC patients were less than 60 years old). Non-alcoholic LC patients had a higher rate of concomitant comorbidities than alcoholic LC (79.6% vs. 68.6%, P＜0.001). LC patients with chronic kidney disease demonstrated the highest adjusted HRs of 2.762 in alcoholic LC patients and 1.751 in non-alcoholic LC patients (all P＜ 0.001). In contrast, LC patients with hypertension and hyperlipidemia had a decreased risk of mortality. However, the six-year survival rate showed no difference between both study groups (P=0.312).

Conclusions: Alcoholic LC patients were younger, and had lower rates of concomitant comorbidities. However, the all-cause mortality was not different between alcoholic and nonalcoholic LC.

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P.042

PPI AFTER BAND LIGATION FOR ESOPHAGEAL VARICES DO NOT DELAY REBLEEDING TIME FROM POST LIGATION RELATED ULCER Wei-Ting Chen, Juei-Seng Wu, Chun-Te Lee, Shih-Chieh Chien, Hung-Chih Chiu, Chiung-Yu Chen Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

食道靜脈瘤結紮後使用氫離子幫浦阻 斷劑無法延遲結紮後潰瘍再出血 陳威廷 吳叡森 李俊德 簡世杰 邱宏智 陳炯瑜 國立成功大學醫學院附設醫院內科部 Background: Esophageal variceal (EV) bleeding is one of the most severe complications in patients with cirrhosis. Band ligation (EVL) is currently the first-line treatment of EV bleeding. After ligation, mucosal ulceration is frequently observed in the esophagus, and routine proton pump inhibitor (PPI) are frequently given. However, the efficacy of post-EVL PPI in preventing ligation related ulcer bleeding is not clear. In this study, we aim to evaluate whether adding PPI after EV ligation can reduce post-EVL related esophageal ulcer bleeding.

Aims: Whether adding PPI after EV ligation can reduce post-EVL related esophageal ulcer bleeding.

Methods: We retrospectively selected patients who received EV ligation for EV bleeding from National Cheng Kung University Hospital during 2013/01/01 to 2018/09/01, and reviewed the findings of initial EGD including the severity of esophageal varices, grade of gastric varices and the presence of peptic ulcers. We also reviewed the patients’ degree of liver cirrhosis (Child-Pugh-Turcotte, CTP, stage) and related comorbidities including HCC, PV thrombosis and renal functions. We included those who rebleed after index EGD within 60 days and redefined the etiology of rebleed. Only those who rebled due to post-EVL related esophageal ulcers were included. A Kaplan–Meier survival analysis and Cox regression model were used to determine factors associated with early rebleed.

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Results: Twenty-eight patients were included for analysis. The median time to rebleed was 10 days (1 to 58 days). There was no significance difference of time-to-rebleed between PPI group and those did not received PPI after index EVL (10 days vs. 8 days, log-rank p=0.425,). However, in the index EGD, patients with gastric varices (4 days vs. 12 days, log-rank p: 0.01), those with peptic ulcers (4 days vs. 12 days, log-rank p: 0.045) rebled earlier. In the Cox-regression model, patients who were younger (＜60 years old vs.＞60, HR: 5.61, 95% CI: 1.66-18.99, p＜ 0.05), had early stage liver disease (CTP stage B vs. A HR: 0.07, 95% CI: 0.02-0.35, p=0.001; CTP-C vs. CTP-A HR: 0.08, 95% CI: 0.01-0.46, p=0.005), and whose initial EGD showed peptic ulcer (HR: 3.17, 95% CI: 1.11-9.11, p=0.03) or gastric varices (HR: 9.87, 95% CI: 3.04-9.11, p=32.11) rebled earlier.

Conclusions: The prescription of PPI cannot prevent early post-EVL related esophageal ulcer bleeding. Presence of gastric varices may associate with higher portal pressure, while peptic ulcer may indicate a vigorous offense factor or an attenuated defense factor for ulcer development.

Therefore, these two factors are associated with early rebleeding.

P.043

GENOTYPE 6 SUBTYPES OF HEPATITIS C VIRUS IN TAINAN, SOUTHERN TAIWAN AND DISTRICT VARIATION OF THE SUBTYPES Jyh-Jou Chen1, Hung-Da Tung1, Hsing-Tao Kuo2, Pei-Lun Lee1, Ming-Jen Sheu2, Li-Ching Wu3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Yongkang, Tainan, Taiwan2 Department of Clinical Pathology, Chi-Mei Medical Center, Yongkang, Tainan, Taiwan3

台南市 C 型肝炎病毒基因型六型亞型 研究及其地理分布的差異 陳志州1 董宏達1 郭行道2 李佩倫1 許銘仁2 吳麗卿3 柳營奇美醫院胃腸肝膽科1 永康奇美醫學中心胃腸肝膽科2 永康奇美醫學中心病理科3 Background: Genotype 6 was the most diverse genotype and comprised of up to 29 subtypes from a to xf. Studies that reported decade ago showed genotype (GT) 1 and GT 2 were the major HCV GTs in Taiwan; however, we had reported higher prevalence (18.3%) of GT 6 in Tainan City that located in southern Taiwan. GT 6 had been reported with major subtypes of 6a and 6n in PWID of patients with HIV infection in Taiwan. Most of our patients who with GT 6 infection that preliminary small number study showed 70% were 6g subtype do not have history of abuse of drugs of HIV infection.

Aims: This study was designed to verify the subtypes of GT 6 in southern Taiwan and its variation in districts of Tainan City.

Methods: A total 348 (155 men and 193 women, mean age, 65.4 + 13.1 years) patients with GT 6 viremia and have stored serum available for subtypes examination, who were followed up in Chi Mei medical system (i.e., Yunkan, Liouying, and Chiali campuses), between 1 Mar 2016 and 28 Feb 2019, were included in this study.

The subtypes of GT6 were determinate with phylogenetic analysis of E1 and NS5B. For NS5B gene analysis, part of NS5B gene (330 bp) and

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E1 gene (750 bp) were amplified by PCR. The PCR products were then sequenced for following phylogenetic tree analysis to determine HCV GTs. MEGA software version 6.0 was used to construct the phylogenetic tree using the neighbor-joining method based on the Kimura 2-parameter distance.

Results: The subtypes determinate is coordinate of E1 and NS5B in 321 (92.2%), including 6g 256 (79.8%), 6w 38 (11.8%), 6a 25 (7.8%), and 6n 2(0.6%), dis-coordinate of E1 and NS5B in 7 (2.0%), un-detective for E1 or NS5B in 17 (4.9%), and un-detective for E1 and NS5B in 3 (0.9%) patients. Two GT 6v and 1 GT 6t found in E1 sequence but not in NS5B sequence. Four GT 6v found by NS5B sequence but not in E1 sequence.

The distribution of subtypes of districts of Tainan that showed geographic variation will describe in report.

Conclusions: The major subtype of GT 6 in Tainan is 6g, follow by 6w. Less than 10% are 6a and 6n. Geographic variation of district of Tainan was found by this study. The 27 samples showed dis-coordinate between E1 and NS5B subtype analysis or undetected of subtype may possibly be novel subtypes of GT 6.

P.044

PREVALENCE AND CLINICAL RELEVANCE OF ISOLATED HEPATITIS B CORE ANTIBODY IN PATIENTS WITH CHRONIC HEPATITIS C Chi-Ching Chen1, Shui-Yi Tung1, Kuo-Liang Wei1, Te-Sheng Chang1, Sheng-Nan Lu1,2, Chao-Hung Hung1,2 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

B 型肝炎核心抗體單獨陽性在慢性 C 型肝炎患者中的盛行率與臨床意義 陳其敬1 董水義1 魏國良1 張德生1 盧勝男1,2 洪肇宏1,2 嘉義長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院胃腸肝膽科系2 Background: Isolated antibody to hepatitis B core antigen (anti-HBc) serological profile is a frequent finding in chronic hepatitis C virus (HCV)infected patients.

Aims: The aim of this study was to determine the prevalence and clinical significance of isolated anti-HBc among chronic HCV-infected patients in Taiwan where hepatitis B virus (HBV) and HCV is highly endemic.

Methods: A total of 303 chronic hepatitis C patients who were tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs) and anti-HBc were included for analysis Results: Of these patients, 21 (6.9%) were HBsAg positive, 132 (43.6%) positive for both antiHBs and anti-HBc, 92 (30.3%) anti-HBc positive alone, 21 (6.9%) anti-HBs positive alone and 37 (12.2%) negative for all HBV markers. Patients with anti-HBc alone had a lower male-female ratio than those with positive HBsAg (p=0.027) and positive anti-HBs/anti-HBc (p=0.040),

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whereas there were no significant differences in other clinical characteristics between groups.

Compared with those previously vaccinated (antiHBs alone), patients with anti-HBc alone were older (p=0.006), higher ratio of cirrhosis (p=0.006) and lower HCV load (p=0.007).

Conclusions: Isolated anti-HBc accounting for 30% of our chronic HCV-infected patients can be attributed to post-HBV infection with a loss of antiHBs. Further studies are necessary to confirm our findings.

P.045

REAL-WORLD EFFECTIVENESS AND SAFETY OF GLECAPREVIR/ PIBRENTASVIR IN ASIAN PATIENTS WITH CHRONIC HEPATITIS C Shih-Jer Hsu1,2, Min-Chin Chiu1,2, Yu-Jen Fang1,2, Tsung-Hua Yang1,2, Jian-Jyun Yu1,2, Chieh-Chang Chen1,3, Chia-Chi Kuo1,2, Ji-Yuh Lee1,2, Chien-Hung Chen1,2,3, Ding-Shinn Chen3,4,6, Jia-Horng Kao3,4,5 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan1 Hepatology Medical Center, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan5 Genomics Research Center, Academia Sinica, Taipei, Taiwan6

Glecaprevir/Pibrentasvir 治療亞洲慢 性 C 型肝炎患者之真實世界成效與安 全性 徐士哲1,2 邱敏欽1,2 方佑仁1,2 楊宗樺1,2 余健鈞1,2 陳介章1,3 郭家旗1,2 李基裕1,2 陳健弘1,2,3 陳定信3,4,6 高嘉宏3,4,5 國立臺灣大學醫學院附設醫院雲林分院內科部1 國立臺灣大學醫學院附設醫院雲林分院肝膽醫學 中心2 國立臺灣大學醫學院附設醫院內科部3 國立臺灣大學醫學院附設醫院肝炎研究中心4 國立臺灣大學醫學院臨床醫學研究所5 中央研究院基因體研究中心6 Background: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Asian patients other than Japanese are limited.

Aims: We aimed to investigate the effectiveness and safety profile of GLE/PIB in Taiwanese

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patients with chronic hepatitis C (CHC).

Methods: CHC patients who received 8, 12, or 16 weeks of GLE/PIB between August and October of 2018 were consecutively enrolled.

The treatment duration was determined according to drug label. The hepatic fibrosis was staged according to liver histology, transient elastography, fibrosis index based on 4 factors (FIB-4), or findings of ultrasonography/endoscopy.

The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed.

Results: A total of 110 CHC patients with 51% of males were enrolled. The median age was 70 years. A majority (82%) of patients were infected with HCV genotype 2. Forty-six (42%) and 64 (58%) patients had advanced hepatic fibrosis and compensated cirrhosis, respectively. Fortyfive (41%) non-cirrhotic patients were treated for 8 weeks. The overall SVR12 rates were 100%, regardless of baseline clinical characteristics.

The common adverse events (AEs) were pruritus (12%), anorexia (6%), and fatigue (5%). Nine (8%) serious AEs unrelated to GLE/PIB occurred.

Three (2%) patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation, or death.

Conclusions: Interferon-free GLE/PIB regimen is highly effective and safe for Asian chronic hepatitis C patients with advanced hepatic fibrosis or compensated cirrhosis.

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P.046

THE BEST TIMING TO RECEIVED ENDOSCPIC HEMOSTASIS IN CIRRHOSIS PATIENT WITH VARICES BLEEDING Wei-Ling Tung, Te-Sheng Chang, Chao-Hung Hung, Kuo-Liang Wei, Chun-Hsien Chen, Chih-Wei Yen Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

胃與食道靜脈瘤出血之肝硬化病人接 受內視鏡止血的適當時機 童威霖 張德生 洪肇宏 魏國良 陳俊憲 顏志維 嘉義長庚紀念醫院 Background: Varices bleeding is one of frequent and important complication in cirrhosis patient which with high risk of mortality. In previous study and Baveno consensus recommend current treatment in varices bleeding including antibiotic, pharmacologic and endoscopic combination as a stander strategy. While patient came to emergency room with symptoms of varices bleeding, antibiotic and vasopressin, somatostatin and their analogues was given immediately upon admission. But the timing of endoscopic treatment still a great concern. Because timing of symptoms presentation, referral to endoscopist and availability of endoscopic facilities still very different in area which may cause the treatment result in various. Also, the view of endoscopic with massive blood or blood clot during procedure will affect the quality and duration of searching bleeder and also cause repeat endoscopic treatment after first endoscopic treatment failure.

Repeating endoscopic treatment considered a mainly safety issue.

Aims: The aim of study was to investigate all varices bleeding patients from emergency room and access the outcomes how the endoscopic timing affect in all aspects.

Methods: A retrospective chart review was performed on all emergency room upper endoscopies performed from January 2009 to December 2014 (total 215 patient) at Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

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Results: There are 215 patient included in our study, we had evaluated all aspects including medication, cirrhosis score (MELD score, Child Pugh score), time to scopy, mortality, hospital stays. And which showed with no significant in mortality between in 3/3~6/or＞6 hours scopy timing. But affect in hospital stays and ICU admission days.

Conclusions: The result of survival rates seems no significant different between emergent endoscopy performed timing in varices bleeding.

P.047

ADVANCED CHRONIC LIVER DISEASE WITH VARICEAL BLEEDING: SINGLE HOSPITAL EXPERIENCE IN NORTHERN TAIWAN Bi-Zhen Kao, Hwai-Jeng Lin, Ming-Yao Chen, Chia-Shin Wu, Sheng-Tsai Lin, Yu-Xin Lai, Ming-Zhe Tay, Chung-Ying Lee Division of Gastroenterology and Hepatology, Department of Internal medicine, Taipei Medical University Shuang Ho Hospital, New Taipei, Taiwan

肝硬化患者合併靜脈曲張破裂出血： 雙和醫院的經驗 高碧珍 林懷正 陳明堯 巫嘉興 林聖才 賴雨欣 鄭明哲 李宗頴 衛生福利部雙和醫院（委託臺北醫學大學興建經 營）消化內科 Background: The gastroesophageal variceal bleeding is 5–11% of all gastrointestinal bleeding and is the cause of 60–65% of the bleeding episodes in patients with advanced chronic liver disease. The mortality rate from each episode of variceal haemorrhage is approximately 15 to 20%. The risk factors for variceal haemorrhage include variceal character (size. red color signs), active alcohol intake, Child-Pugh-Turcotte (CPT) Grade B or C, liver stiffness more than 25 KPa, thrombocytopenia, presence of ascites, poral vein thrombosis and bacterial infection.

Aims: To study nature of patients with advanced chronic liver disease and variceal bleeding and mortality.

Methods: A retrospective study of patients with advanced chronic liver disease and variceal bleeding accepting endoscopic treatment from 2013 to 2018 at Taipei Medical University ShuangHo hospital. Endoscopic variceal treatment was variceal ligation for esophageal variceal bleeding and local cyanoacrylate injection for gastric variceal bleeding.

Results: Out of 263 enrolled cases of variceal bleeding, 24 cases (9.12%) were gastric variceal bleeding and 239 case (90.88%) were esophageal variceal bleeding. Alcohol related cirrhosis was 122 patients (46.39%); and nonalcoholic cirrhosis (53.61%) included chronic

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hepatitis B (52 patients, 36.8%), chronic hepatitis C (22.69%), both chronic hepatitis B&C (4.96%), autoimmune hepatitis (3.55%) and unknown aetiology (31.91%). Male dominated the sample population (73.38%), and it was much significant in alcoholic cirrhosis compared to non-alcoholic cirrhosis (91.80% Vs 57.45%, p＜0.0001). Mean age was 54 + 14.45 years and alcoholic cirrhotic patient were younger than non-alcoholic patients (49.0 + 10.20 years Vs 61.0 + 13.68 years, p＜ 0.0001). Thrombocytopenia was noted in 170 patients (67.68%) and 74.77% of patients were CPT grade B or C. Compared to non-alcoholic patients, alcoholic patients had higher CPT score (8.61 + 2.03 Vs 7.89 + 2.50, p=0.0114) and MELD score (18.48 + 7.43 Vs 16.51 + 6.53, p=0.0228). In our analysis, 27.75% of the patients had hepatocellular carcinoma (alcoholic patients Vs non-alcoholic patients: 37.59% vs 16.39%, P=0.0001). Overall malignancy prevalence was also higher in non-alcoholic patients (49.64% Vs 22.95%, p＜0.0001). Diabetes mellitus was associated in 82 patients (31.17%), significantly more in non-alcoholic patients (41.84% Vs 18.85%, p＜0.0001). Mortality within 30 days after first episode of variceal bleeding was 12.17% (alcoholic patients Vs non-alcoholic patients: 9.02% Vs 14.89%), 3-months mortality was 23.28% and 6-months mortality was 36.71% (alcoholic patients Vs non-alcoholic patients: 27.69% Vs 46.51%, P=0.0017).

Conclusions: With our hospital data base, on the variceal bleeding episode, the patients with alcoholic advanced liver disease were younger age, significant male sex, higher CPT score & MELD score, less association with malignancy including HCC and diabetes mellitus and less mortality rate, as compared to the patients with non-alcoholic advanced liver disease.

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P.048

PROJECTION OF HEALTH OUTCOMES OVER 5-YEAR AND 10YEAR PERIOD USING TENOFOVIR ALAFENAMIDE (TAF) FOR THE MANAGEMENT OF CHRONIC HEPATITIS B (CHB) IN CHINA Ying Han1, Bin Wu2, Ming Hu3, Fengqin Hou4, Yida Yang5, Lei Wang6 Xijing Hospital of the 4th Military Medical University, Xi’an, China1 Renji Hospital of Shanghai Jiaotong University, Shanghai, China2 Huaxi Healthcare Policy and Pharmacoeconomics Research Centre, Sichuan University, Chengdu, China3 The 1st Hospital of Peking University, Beijing, China4 The 1st Affiliated Hospital of Zhejiang University, Hangzhou, China5 The 2nd Hospital of Shandong University, Jinan, China6 Background: The burden of CHB infection in China is high, with an estimated 96 million patients. The goal of therapy is to suppress viral replication and achieve normalization of alanine aminotransferase (ALT) levels to reduce related liver complications such as compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC).

Aims: In this study, we simulated the health consequences of nuecleos(t)ide analog (NA) therapies on 100,000 Chinese CHB patients comparing TAF to tenofovir disoproxil fumarate (TDF) and entecavir (ETV).

Methods: A health outcomes model was developed using an individual patient simulation framework. Model inputs were sourced from randomized controlled trials and peer-reviewed Chinese literature and validated by a panel of Chinese hepatologists. The model assumed that 90% of patients in the overall population were treatment-experienced (TE), of which 27% were assumed to have lamivudine (LAM) experience.

The 5-year and 10-year risks for developing CC and HCC were calculated based on REVEAL score, taking into account early ALT normalization.

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Results: Over the 5-year and 10-year period, patients treated with TAF were expected to experience less liver complications including CC, DCC, and HCC compared to TDF and ETV (Table 1). Specifically, compared to TDF and ETV, with TAF the rates of HCC were reduced by 13% and 31% over the 5-year projection.

Conclusions: TAF is projected to have fewer hepatic complications when compared to TDF and ETV over 5-year and 10-year time period, driven by its favorable efficacy and resistance profile.

P.049

PORTABLE ABDOMINAL SONOGRAPHIC FINDINGS AND CHARACTERISTICS OF HOMECARE USERS AND INSTITUTION RESIDENTS IN THE COMMUNITY Min-Kai Liao1, Chih-Lin Lin1, Tsung-Jung Lin1, Tai-Yin Wu2, Kuan-Yang Chen1 Department of Gastroenterology, Taipei City Hospital, Renai Branch, Taipei, Taiwan1 Department of Family Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan2

社區居家醫療病人與安養機構住民行 動超音波分析 廖敏凱1 林志陵1 林聰蓉1 吳岱穎2 陳冠仰1 臺北市立聯合醫院仁愛院區消化內科1 臺北市立聯合醫院仁愛院區家庭醫學科2 Background: Home-care users and institution residents are thought to receive insufficient medical care due to their inconvenience to visit the hospital.The integrated home care program aims to improve medical accessibility in Taiwan.

However, abdominal ultrasonography is not regularly done during medical contacts.

Aims: We aimed to report our experiences of the portable abdominal ultrasonography in home-care and institution participants in the community in Taipei.

Methods: We enrolled two groups of participants: (1) Home-bound cases of the integrated home healthcare program of Taipei City Hospital, Renai Branch. (2) Residents of a nursing home which is affiliated with Taipei City Hospital, Renai Branch from January 1 to December 31, 2017. All of the participants received portable abdominal ultrasonography examination by physicians during regular home visits and institution visits.

Results: The 132 participants included 44 homecare users and 88 institution residents. The age of home-care group was older than the institution group (86±8.85 VS. 81.55±10.46, p=0.017).

Diabetes mellitus (22.7%), hypertension (22.7%), and cerebral vascular events (18.2%) were the three most common underlying diseases of home care patients. The most common abdominal ultrasonography findings were fatty liver (25.0%) and gallbladder stones (20.5%). Compared to institution residents, home care users had

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higher proportion (38.6% V.S 8.0%, p＜0.001) of hepatobiliary findings, mainly liver cirrhosis. The proportion of other findings showed no significant difference between two groups.

Conclusions: Portable abdominal ultrasonography improved the accessibility of medical service.

Examination performed by physicians during regular home visits and institution visits may help to satisfy the unmet needs of image examination of the disabled elderly.

P.050

EFFICACY AND SAFETY OF ONEYEAR SWITCHING TO TENOFOVIR ALAFENAMIDE FOR CHRONIC HEPATITIS B PATIENTS IN THE REAL-WORLD CLINICAL PRACTICE Szu-Jen Wang1,2, Ching-Yang Tsai2, His-Jung Chen2, Ching-Yang Tsai2, Chia-Yen Dai3, Ming-Lung Yu3 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan2 Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3

慢性 B 型肝炎患者轉換口服抗病毒藥 物 TAF 一年後療效及安全性評估 王嗣仁1,2 蔡青陽2 陳錫榮2 孫盟舜2 戴嘉言3 余明隆3 高雄醫學大學臨床醫學研究所1 阮綜合醫療社團法人阮綜合醫院消化內科2 高雄醫學大學附設中和紀念醫院肝膽胰內科3 Background: Comparing to tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF) therapy reveals higher chance of alanine aminotransferase (ALT) normalization and better safety profiles for renal injury and bone loss in the clinical trials for chronic hepatitis B (CHB). We investigated the efficacy and renal safety issues of TAF switching in the real-world clinical practice.

Aims: We investigated the efficacy and renal safety issues of TAF switching in the real-world clinical practice.

Methods: A total of 50 CHB patients treated with TAF switching from other nucleot(s)ide analogues (NUC) for more than 12 months were enrolled in our hospital. Patients with liver decompensation or end stage renal diseases at TAF switching were excluded. The CKD-EPI equation was used for glomerular filtration rate (GFR) estimation.

Results: A total of 50 CHB patients treated with TAF switching from other nucleot(s)ide analogues (NUC) for more than 12 months were enrolled in

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our hospital. Patients with liver decompensation or end stage renal diseases at TAF switching were excluded. The CKD-EPI equation was used for glomerular filtration rate (GFR) estimation.

Conclusions: The one-year TAF switching in NUC treated CHB patients (majority under TDF treatment) showed the same efficacy in viral suppression and increasing ALT normalization in the real-world clinical practice. In addition, the benefits of renal safety were also noted, esp. in CKD stage II patients. However, lipidprofile changes (increasing total cholesterol and LDL level) were incidental found. But ratio of total cholesterol and HDL was not significantly increased.

P.051

EFFICACY AND SAFETY OF TENOFOVIR ALAFENAMIDE TREATMENT FOR CHRONIC HEPATITIS B PATIENTS WITH FLARE-UP IN THE REAL-WORLD CLINICAL PRACTICE Szu-Jen Wang1,2, Ching-Yang Tsai2, His-Jung Chen2, Meng-Shun Sun2, Chia-Yen Dai3, Ming-Lung Yu3 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan2 Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3

慢性 B 型肝炎急性發作患者使用 TAF 的療效及安全性評估 王嗣仁1,2 蔡青陽2 陳錫榮2 孫盟舜2 戴嘉言3 余明隆3 高雄醫學大學臨床醫學研究所1 阮綜合醫療社團法人阮綜合醫院消化內科2 高雄醫學大學附設中和紀念醫院肝膽胰內科3 Background: Comparing to tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF) therapy reveals higher chance of alanine aminotransferase (ALT) normalization and better safety profiles for renal injury and bone loss in the clinical trials for chronic hepatitis B (CHB). We investigated the efficacy and renal safety issues of TAF treatment for chronic hepatitis B patients with Flare-up in the real-world clinical practice.

Aims: We investigated the efficacy and renal safety issues of TAF treatment for chronic hepatitis B patients with Flare-up in the real-world clinical practice.

Methods: Total 17 CHB patients were enrolled treated with TAF＞12 months due to chronic hepatitis B with flare-up, including 15 (88%) naïve patients and 2 (12%) relapsed patients. Patients with liver decompensation or end stage renal diseases at CHB with flare-up were excluded.

The CKD-EPI equation was used for glomerular

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filtration rate (GFR) estimation.

Results: At the starting time of TAF treatment, the median eGFR was 105.3 (81.6-113.8) ml/ min/1.73m2 (11 [64.7%] had CKD stage I and 6 [35.3%] had CKD stage II) and median log10 HBV-DNA was 5.9 (4-6.8). Median ALT level was 43 (30-60) IU/ml. Mean age was 51.6±11.3 years. HBeAg-negative and HBsAg＞250 IU/ml patients accounted for 82.4% (n=14), respectively. All patients had undetectable HBV DNA at 48 weeks of TAF treatment (p＜0.05).

ALT significantly decreased from 43 (30-60) to 20 (15.5-38.8) U/L (p＜0.01) by using AASLD criteria after 48 weeks of TAF treatment. The rate of ALT normalization increased from 17.6% to 64.7% (p ＞0.05). The eGFR decreased from 105.3 (81.6113.8, at baseline) to 92.9 (76.7-112.1, at 48week TAF treatment) ml/min/1.73m2 (p＞0.05).

Conclusions: 48-week TAF treatment in CHB with flare-up patient showed the great efficacy in viral suppression and increasing ALT normalization in the real-world clinical practice.

However, the benefits of renal safety were not found in this observational study maybe due to limited case numbers or not marked improvement in CKD stage I/II patients. This needs further studies to elucidate the profiles of renal safety in TAF treatment.

P.052

FACTORS ASSOCIATED WITH CRYOGLOBULINEMIA RESOLUTION IN CHRONIC HEPATITIS C VIRUS INFECTED PATIENTS AFTER DIRECTANTIVIRAL THERAPY Yu-Ju Wei1, Chung-Feng Huang1,3, Ming-Lun Yeh1,3, Jia-Jung Lee2,3, Po-Cheng Liang1, Yi-Hung Lin1, Cheng-Ting Hsu1, Po-Yao Hsu1, Meng-Hsuan Hsieh1,3, Tyng-Yuan Jang1, Ta-Ya Lin1, Shinn-Cherng Chen1,3, Zu-Yau Lin1,3, Chia-Yen Dai1,3, Jee-Fu Huang1,3, Ming-Lung Yu1,3, Wan-Long Chuang1,3 Division of Hepatobiliary,Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan3

影響慢性 C 型肝炎患者接受口服小分 子抗病毒藥後冷凝球蛋白血症改善的 因素 魏鈺儒1 黃釧峰1,3 葉明倫1,3 李佳蓉2,3 梁博程1 林宜竑1 徐成鼎1 許博堯1 謝孟軒1,3 張庭遠1 林大雅1 陳信成1,3 林子堯1,3 戴嘉言1,3 黃志富1,3 余明隆1,3 莊萬龍1,3 高雄醫學大學附設醫院內科部肝膽胰內科1 高雄醫學大學附設醫院內科部腎臟內科2 高雄醫學大學醫學院內科3 Background: Hepatitis C virus (HCV) infection is the main etiology of mixed cryoglobulinemia, accounting for 80% of cryoglobulinemia.

Mixed cryoglobulinemia is the most important extrahepatic manifestation of chronic HCV infection. Cryoglobulinemia may increase nonliver-related mortality, affecting quality of life and economic burden.

Aims: This study aimed to identify the risk

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factors associated with cryoglobulinemia and its resolution in chronic HCV infected patients after HCV eradication.

Methods: A total 426 chronic hepatitis C (CHC) patients receiving direct antiviral (DAAs) treatment during 2014.01~2018.07 were recruited. The status of cryoglobulin at baseline and after treatment were assessed. Clinical profiles were also collected in order to elucidate the predictors for the recovery of cryoglobulinemia.

Results: The mean age was 63.41±11.4 years.

The prevalence of cryoglobulinemia was 124/426 (29.1%). These patients with cryoglobulinemia were female predominant (68.5%, P=0.026) and had lower serum platelet (148.9±71.0 x 103/ uL, P=0.004), higher aspartate aminotransferase (85.67±57.33 U/L, p=0.029), lower gammaglutamyltransferase (47.83±38.28 U/L, p=0.004), lower triglycerides (90.29 ±40.99 mg/dL, P=0.010), lower HCV RNA (5.29±0.98 Log IU/ mL, P＜0.001), and higher Fib-4 ( 5.03±3.98, P=0.003) compared to their counterparts. They also had a significantly lower sustained virologic response (SVR) rate (97.6% vs ??%, P=0.042) than those without cryoglobulinemia. HCV RNA (odds ratio: 0.311, confidence interval 0.20-0.50, P＜0.001) was the only factor associated with cryoglobulinemia in multivariate analysis. Eightyeight (71%) of the 124 cryoglobulinemia patients at baseline recovered to be cryoglobulinemianegative 12 weeks after end of treatment (M3).

The factors associated with cryoglobulinemia resolution were younger age (63.38±10.33 years), lower high-density lipoprotein cholesterol (HDL-C) (47.82±13.40 mg/dL, P=0.002), higher triglycerides (97.45±44.51 mg/dL, P＜0.001), higher HCV RNA (5.46±0.91 Log IU/mL, P＜ 0.001), and higher SVR rate (100%, P=0.006). In multivariate analysis, higher HDL-C (odds ratio: 5.56, confidence interval 1.20-25.83, P=0.028) and lower HCV RNA (odds ratio: 7.13, confidence interval 1.56-32.61, P=0.011) were significant associated with cryoglobulinemia resolution at M3.

Conclusions: The prevalence of cryoglobulinemia was not rare among CHC patients. Successful eradication of HCV by DAAs recovers cryoglobulinemia, particularly in patients with a higher HDL-C and a lower HCVRNA level.

P.053

FIBROINDEX PREDICTS SUBSEQUENT ESOPHAGEAL VARICEAL BLEEDING IN COMPENSATED CIRRHOTIC PATIENTS WITH INITIAL SMALL VARICES WITHOUT BETABLOCKER PROPHYLAXIS Sheng-Fu Wang1, Chien-Hao Huang1,2, Yu-Ling Chen3, Pin-Cheng Chen1, Bo-Huan Chen1, Wen-Juei Jeng1,2, Yi-Chung Hsieh1,2, Wei Teng1,2, Yi-Cheng Chen1,2, Yu-Pin Ho1,2, Chun-Yen Lin1,2, I-Shyan Sheen1,2 Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Center for Big Data Analytics and Statistics3

利用 Fibroindex 在代償性肝硬化病人 身上預測小性食道靜脈瘤之出血 王昇富1 黃建豪1,2 陳妤昤3 陳品錚1 陳博煥1 鄭文睿1,2 謝彝中1,2 滕威1,2 陳益程1,2 何玉彬1,2 林俊彥1,2 沈一嫻1,2 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 巨量資料分析中心3 Background: Esophageal variceal bleeding is a common clinical manifestation of liver cirrhosis whatever etiology, which result in recurrent hospitalization despite improvement of endoscopic therapy and medication usage.

In addition, the variceal bleeding due to the rupture of varices is still the most common lethal complication of cirrhosis [1]. Therefore, selecting high risk patients to have preventive strategy seems to be crucial.

Aims: To predict subsequent esophageal variceal (EV) bleeding within 1 year and 2 years in compensated liver cirrhotic patients with initial small esophageal varices without beta-blocker prophylasix by non-invasive of markers.

Methods: The data source was obtained from the database center for big data analytics and statistics of Chang-Gung Memorial Hospital

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(CGRD) after IRB approval. Non-invasive parameters including CTP score, MELD score, MELD-Na score, PALBI score, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), gammaglutamyl transpeptidase-to-albumin ratio (GAR), AST/ALT, AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), spleen diameter, portal vein size, fibrosis-4-index (FIB-4), fibrosis index (FI), King’s Score, Log score, Lok index, and Forn’s index were measured to predict esophageal bleeding within 1 year and 2 years.

Results: The study included 6803 cirrhotic patients with small EV, no red-color sign, who had not used non-selective beta-blocker until event of EV bleeding. 539 patients (7.92%) and 710 patients (10.44%) had esophageal variceal bleeding within in 1 year and 2 years, respectively.

By multivariate analysis, the FI (1 year: HR: 1.442; 95% CI: 1.285-1.619; 2 years: HR:1.41; 95% CI: 1.28-1.55, p＜0.001), GPR, and gender had significant prediction abilities of EV bleeding within 1 year and 2 years, in which fibrosis index possesses the best AUROC of 0.630 and 0.623 respectively.

Conclusions: Fibrosis index is the best predictor of subsequent EV bleeding in compensated cirrhotic patients with initial small EV without betablocker prophylasix.

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P.054

INCIDENCE AND RISK FACTORS FOR ON-TREATMENT ABNORMAL LIVER FUNCTION IN CHRONIC HEPATITIS C PATIENTS RECEIVING DIFFERENT DIRECT-ACTING ANTIVIRAL AGENTS Yen-Chun Liu1,2, Wen-Juei Jeng1,2, Ya-Ting Cheng1,2, Yi-Chung Hsieh1,2, Yi-Cheng Chen1,2, Chun-Yen Lin1,2, Rong-Nan Chien1,2, I-Shyen Sheen1,2 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

慢性 C 型肝炎使用直接作用抗病毒藥 物時發生肝功能異常發生率與危險因 子 劉彥君1,2 鄭文睿1,2 鄭雅婷1,2 謝彝中1,2 陳益程1,2 林俊彥1,2 簡榮南1,2 沈一嫻1,2 林口長庚紀念醫院胃腸肝膽科系1 長庚大學2 Background: Abnormal liver function (LFT) is an uncommon but noticeable adverse event for chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAA).

Aims: To investigate the incidence and predictors for abnormal liver function during DAA treatment.

Methods: CHC patients with interferon-free DAA treatment in Chang Gung Memorial Hospital were recruited. Serum alanine transferase (ALT) and bilirubin level were measured at baseline, 2nd, 4th, 8th, and 12th/24th weeks during treatment.

“Abnormal ALT” was defined as ALT level＞ 1.1 times (X) of baseline and＞1.25X than the upper limit of normal (ULN) values. Age, gender, cirrhosis, HCV genotype and viral load, baseline hemogram, biochemistry and metabolic profiles were compared between patients with and without on-treatment abnormal liver function.

Results: A total of 1532 CHC patients receiving DAA treatment (139 DCA/ASV, 697 Sofo-based DAA, 324 PrOD, 229 Zepatier, and 143 Maviret) were analyzed. On-treatment ALT elevations was observed in 13.8% patients, majorly treated with DCV/ASV (56/139) followed by Zepatier (32/229)

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and least with Maviret (8/143). Abnormal ALT elevation grade III occurred in 10/32 patients with Zepatier, 10/56 with DCA/ASV, 6/35 with Pro-D, 8/81 with Sofo-based and none with Maviret. Time to abnormal ALT level occurred earlier in patients treated with Pro-D (median: 28 days) while latest with DCA/ASV (median: 84 days). Total bilirubin level elevation was observed in 19.6% patients and grade III abnormality occurred majorly in patients treated with Pro-D (13/94). SVR 12 rate comparable in patients with and without abnormal LFT (table). Early DAA termination due to abnormal LFT occurred in 7/212 patients (2 DCA/ ASV, 4 Pro-D, one Zepatier). Only 3/7 patients (43%) with early termination of DAA achieved SVR12. By multivariate logistic regression analysis, HbA1c 36.5 [aOR: 1.24 (1.07-1.43), P=0.004], co-infection with HBV [aOR: 3.427 (1.868-6.288), P0.001] baseline ALT 1X ULN [15X ULN: 3.46 (1.70-7.05), P 0.001; 3 5X ULN: 5.05 (1.86-13.68), P=0.001] and patients treated with DCA/ASV [aOR: 6.3 (2.35-16.93), P0.001] were independent risk factors for on-treatment ALT elevation.

Conclusions: On-treatment ALT elevation is not a rare event during DAA therapy, (13.8%) with high HbA1c, high baseline ALT and DCA/ASV as independent risk factors. Early termination (3.3%) due to abnormal LFT may lead to unsatisfactory SVR12 rate.

P.055

REAL-WORLD EXPERIENCE OF GLECAPREVIR AND PIBRENTASVIR (GP) TREATMENT IN UREMIA PATIENTS WITH CHRONIC HEPATITIS C IN CHIAYI: ONE DEATH AND ONE WITHDRAWAL CHIA-YI, TAIWAN Chi-Yi Chen, Ming-Tse Hsu, Tsung-Jung Tsai, Yu-Min Feng, Chien-Chung Fang, Po-Yueh Chen Division of Gastroenterology, Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan

GP 治療 C 型肝炎洗腎病人的台灣健保 經驗：100% SVR 陳啟益 許銘澤 蔡崇榮 酆裕民 方建忠 陳柏岳 嘉義基督教醫院胃腸肝膽科 Background: The efficacy and safety of GP has been reported in numerous clinical studies. GP is the first pangenotypic DAA drug in Taiwan. In Taiwan, GP was reimbursed from 2018, August.

Limited realworld evidences of GP in uremic patients with HCV in high prevalent Chia-Yi, Taiwan are available.

Aims: To investigate the efficacy and safety of 12-week and 8-week GP treatment in Uremic patients with HCV infection by analyzing the clinical data from Chia-Yi Christian Hospital.

Methods: We collected 100 uremic patients with regular hemodialysis and HCV infection from Jan. 2018 to Jun, 2019. There were 62 HCV infected uremic patients received GP treatment.

Results: Overall, 60 patients received GP completed 8 weeks (38 patients) and 12 weeks (22 patients) treatment with the result of 100% SVR. During this period of GP treatment, only one death due to sepsis (2-3 weeks after GP) and on GP withdrawal due to severe itching and poor intolerance (8-9 weeks after GP). Adverse effect of itching were detailed review. There were no any itching noted in 48 patients with GP (77.4%).

Active itching with chief complaints noted in 6 patients (tropical drugs 6, anti-histamine drugs 5, both 5). Significant itching rate was 9.6% with

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itching-withdrawal rate 1.6%. Mild itching and passive remind noted in 8 patients (12.9%).

Conclusions: The overall SVR rate in uremic patients with hemodialysis was 100% (PP) and 96.7% (ITT). Only one itching related discontinuation was noted. The withdrawal rate was 1.6%. One death during GP therapy was revealed due to sepsis. The mortality rate of GP in uremic patients was 1.6%.

P.056

REMARKABLE DIFFERENCE IN RE-TREATMENT RESPONSE IN PATIENTS WITH DIFFERENT HBSAG/ALT KINETICS DURING OFF-NUC HEPATITIS FLARE Wen-Juei Jeng1,2, Yen-Chun Liu1,2, Rong-Nang Chien1,2,3, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan3

停止 B 肝口服抗病毒藥物之患者在肝 炎發作時的不同表面抗原定量與丙氨 酸轉氨酶的動力學表現造成再次治療 反應的顯著差異 鄭文睿1,2 劉彥君1,2 簡榮南1,2,3 廖運範2,3 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 林口長庚紀念醫院肝臟研究中心3 Background: Off-Nuc hepatitis flare (AE: ALT ＞5X ULN) with deceasing qHBsAg may reflect successful immune clearance whereas those with increasing qHBsAg reflect ineffective immune response.

Aims: To investigate whether AE with different pretherapy HBsAg/ALT kinetics showed different re-treatment response Methods: HBeAg-negative off-Nuc AE with qHBsAg at 3 time points (pre-flare, during flare, months 6 and/or 12 of re-treatment) were studied.

Pre-treatment ALT, HBV DNA and qHBsAg levels, on-treatment start to ALT normalization, undetectable HBV DNA, the presence of rapid HBsAg decline (HBsAg decline 0.5 log10 in 6 months or 1 log10IU/ml in 12 months) during retreatment were compared between patients with different pretherapy HBsAg/ALT kinetics. Logistic regression was applied.

Results: Of 202 patients with off-Nuc flare, 18.8% showed decreasing qHBsAg (group I) and 81.2% showed increasing qHBsAg (group II). The two groups were comparable in demographic features, previous treatment and consolidation

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duration, but higher end of treatment (EOT) qHBsAg in group I (median: 2.9 vs. 2.7 log10IU/ ml, P=0.001). At the start of retreatment, group I patients had lower ALT level (median: 251 vs.

388 U/L, P=0.0001), lower HBV DNA level (5.8 vs. 6.7 log10IU/ml, P=0.0002) and lower qHBsAg level (2.7 vs. 3.4 log10IU/ml, P＜0.0001). During retreatment, “rapid HBsAg decline” occurred in 73.2% of group II vs. 7.9% of group I patients (P ＜0.0001), median qHBsAg decline by month 12 was -0.07 log10IU/ml vs. -0.91 log10IU/ml (Figure).

Higher ALT level ( 10X ULN vs 5-10X ULN, aOR: 2.8 (1.3-6.2), P=0.008), higher HBV DNA level [ 7 log10IU/ml: aOR: 3.5 (1.2-10.2), P=0.219], higher qHBsAg level [aOR: 4.1 (1.8-9.5), P=0.003] at start of retreatment and group II patients [vs. group I: aOR: 19.6 (4.8-80.7), P＜0.001] were independent factors for “rapid HBsAg decline”.

Remarkably, 78.9%, 13.2% of group I vs. 26.2%, 0% of group II patients showed stationary and increased qHBsAg level respectively at month 12 (P＜0.0001).

Conclusions: Patients with decreasing qHBsAg during off-Nuc AE showed minimal decline or even increasing qHBsAg during retreatment.

Perhaps retreatment in such patients is too soon that halt endogenous immune control. Further observation is necessary to decide the necessity or timing of retreatment.

P.057

HISTOLOGIC STEATOSIS IS NOT A FACTOR FOR TUMOR RECURRENCE IN HEPATOCELLULAR CARCINOMA PATIENTS RECEIVING CURATIVE HEPATECTOMY Po-Ting Lin1, Tsung-Han Wu2,3, Wei Teng1,3, Wen-Juei Jeng1,3, Chun-Yen Lin1,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 College of Medicine, Chang Gung University, Taoyuan, Taiwan3

肝脂肪變性對於肝癌病人接受根除性 手術治療後腫瘤復發機率的影響及比 較 林伯庭1 吳宗翰2,3 滕威1,3 鄭文睿1,3 林俊彥1,3 林口長庚紀念醫院胃腸肝膽科系1 林口長庚紀念醫院一般外科系2 長庚大學醫學院3 Background: Surgical resection provides the lowest recurrence rate apart from liver transplantation for patients with hepatocellular carcinoma (HCC). Increased prevalence of fatty liver in recent decades has been an important health issue but its impact on HCC recurrence remains uncertain.

Aims: This study was aimed to investigate the impact of hepatic steatosis and the predictive factors for tumor recurrence in HCC patients after curative hepatectomy.

Methods: From 2015 to 2019, treatmentnaive HCC patients receiving hepatectomy in Chang Gung Memorial Hospital, Linkou medical center were prospectively recruited. Baseline characteristics before surgery including age, gender, lipid profile, liver function and cirrhotic parameters as well as pathology finding including cirrhotic stage, fatty change of liver, microvascular invasion of tumor, surgical margin were analyzed and compared between patients with and without HCC recurrence. Cox regression analysis was applied for the predictive factors for HCC recurrence.

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Results: Among the 93 patients recruited, the median age was 59.3 (35.5-80.9) years old, and 80.4 % were male. HCC recurrence events were documented in 10 patients (10.8%) with median follow-up duration 18.3 months. Patients with cirrhosis, advanced tumor stage, tumor having microvascular invasion, and less surgical margin were prone to encounter HCC recurrence. Though patients with histologic finding with steatosis＞ 33% had mild higher recurrence rate compared to those without, yet not reach statistical significance (40% vs. 21.7%, P=0.2395). Multivariate Cox regression analysis revealed that cirrhotic patients and tumor with microvascular invasion were the independent predictive factors for HCC recurrence. Cirrhotic patients have higher early HCC recurrence rate than non-cirrhotic patients (2-years: 33% vs. 12%, P=0.047).

Conclusions: The presence of hepatic steatosis is not an independent factor for HCC recurrence in patients received curative resection. Cirrhosis and microvascular invasion were the independent predictors for HCC recurrence.

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P.058

TRANSIENT INCREASED ENDSTAGE LIVER DISEASE SCORE (MELD) AFTER SOFOSBUVIR PLUS RIBAVIRIN IN LIVER CIRRHOSIS GENOTYPE 2 HEPATITIS C PATIENTS Po-Ke Hsu, Pei-Yuan Su, Cheng-Da Yang, Yu-Chun Hsu, Yang-Yuan Chen, Wei-Wen Su Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

治療基因型第二型肝硬化的病人 MELD 暫時性上升 許柏格 蘇培元 楊承達 徐有春 陳洋源 蘇維文 彰化基督教醫院肝膽胃腸科 Background: Hepatitis C virus (HCV) is one of the major globally cause of death and recent estimates showed an increase in its seroprevalence over the last decade to 2.8%, corresponding to ＞185 million infections worldwide. There are six genotypes of hepatitis C, and the prevalence of the second type in Taiwan is 64.3%. Hepatitis C, previously used for genotype 2, has sofosbuvir + ribavirin and is quite effective. In this study, we investigated the liver function recovery of genotype 2 patients with hepatitis C. Aims: Using MELD score to demonstrate the recovery of liver function in patients with genotype 2 genotype treated with sofosbuvir + ribavirin and reference for liver transplantation and prognosis.

Methods: We retrospectively collected 58 patients with fibrosis score 3 to 4 with hepatitis C genotype 2 and treated from January 10, 2019 to June 14, 2019 in Changhua county. There patents has liver cirrhosis child A with well compensated liver function and all achieved end of treatment virologic response (ETVR) and also sustained virologic response (SVR) at 12 weeks. We examined the difference between Model For EndStage Liver Disease (MELD) score (creatinine, INR, total bilirubin) at the beginning of treatment and the time points of ETVR and SVR and then analysis. We also analyzed the comparison of MELD with a decrease in hemoglobin of more than 2 g/dl and a decline within 2 or a rising group of MELD at the beginning of treatment and at the

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end of treatment and at the time of SVR. Results: The average patient’s hemoglobin treatment decreased by 1.6 g/dl at the end of treatment. All patients with initial MELD: 7.07 and at time of ETVR: MELD: 7.7 and at time of SVR: MELD: 7.5. At group of hemoglobin decreased with 2 g/dl or increased after direct antiviral treatment, initial MELD: 6.9, at time of ETVR: MELD: 7.6, and at time of SVR: MELD: 7.5 compared to the group of hemoglobin decreased hemoglobin more than 2 showed: initial MELD: 7.2, ETVR: MELD-ETV: 7.7, SVR: MELD: 7.5.

Compared to at time of ETVR, two groups showed significant 7.7 vs 7.5 P＜0.0.5. In whole 58 patients, initial MELD was increased to ETVR and decreased at the time of SVR. Conclusions: Sofosbuvir + ribavirin is effective for the treatment of type 2 hepatitis C. However, the MELD score will increase at the end of treatment, but it will start to decrease in SVR, suggesting that the prognosis of the patient’s liver may be reduced just after treatment. In the long run, it may improve the prognosis of patients.

P.059

THE INCIDENCE AND PREDICTORS OF HBV RELAPSEAFTER CESSATION OF EITHER ENTECAVIR OR TENOFOVIR THERAPY IN PATIENTS WHO ACHIEVED END-OF-TREATMENT HBSAG ≤100 IU/ML Tzu-Ning Tseng1, Chien-Hung Chen2, Tsung-Hui Hu2, Jing-Houng Wang2, Chao-Hung Hung2,3, Sheng-Nan Lu2,3 Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan3

慢性 B 型肝炎病人停止貝樂克或惠立 妥治療且治療結束到達表面抗原小於 100 IU/mL B 型肝炎病毒復發的發生率 和預測因子 曾子寧1 陳建宏2 胡琮輝2 王景弘2 洪肇宏2,3 盧勝男2,3 長庚醫療財團法人高雄長庚紀念醫院內科部1 長庚醫療財團法人高雄長庚紀念醫院胃腸膽科系 暨長庚大學醫學系2 長庚醫療財團法人嘉義長庚紀念醫院胃腸膽科3 Background: Recent studies suggested that HBsAg ≤100 IU/mL was an optimal value for stopping nucleos(t)ide analogues (NA) therapy.

A i m s : To i n v e s t i g a t e t h e i n c i d e n c e a n d predictors after cessationofeither entecavir or tenofovirdisoproxilfumarate (TDF) therapy in patients who achieved end-of-treatment HBsAg ≤100 IU/mL. Methods: A total of 131 patients who had stopped entecaviror TDFtreatment for at least 6 months and achieved end-of-treatment HBsAg ≤100 IU/ mL. All patients in the discontinued group fulfilled the stopping criteriaproposed by the APASL 2012

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guideline.

Results: The 5-year incidences of post-treatment virological and clinical relapse and HBsAg loss were 41.1%, 32.7%, and 50.5%. There was no significant difference in terms of virological relapse (P=0.21), clinical relapse (P=0.43) and HBsAg loss (P=0.25) between patients who discontinuedentecavir and TDF therapy.

Multivariate analysis showed that baseline HBV DNA and end-of-treatment HBsAg levels were independent factors of virological and clinical relapse, and end-of-treatment HBsAg level was an independent factor of HBsAg loss. HBcrAg levelswere not significant factors of HBV relapse.

The HBsAg levels of 40 IU/mL and HBV DNA levels of 5000 IU/mL were best cut-off values to predict HBV relapse by time-dependent ROC curve. The incidence of virological relapse at 5 years in patients with end-of-treatment HBsAg ≤100 and＞100 IU/mL were 59.5% and 16.8% (P ＜0.001), respectively, and clinical relapse were 57.7% and 10.7% (P＜0.001), respectively. The incidences of virological and clinical relapse at 5 years were 5.9% and 2.9%, respectively, in patients with combination of HBsAg levels ≤40 IU/ mL and baseline HBV DNA levels ≤5000 IU/mL. Conclusions: TheHBsAg level of 40 IU/mL was an optimal value to stop NA therapy. There was no significant difference in HBV relapse after cessation of eitherETV or TDF therapyin patients who achieved end-of-treatment HBsAg ≤100 IU/ mL.

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P.060

TWO DIMENSIONAL- VERSUS POINT- SHEAR WAVE ULTRASOUND ELASTOGRAPHY IN ASSESSING HEPATIC FIBROSIS FOR CHRONIC HEPATITIS C USING TRANSIENT ELASTOGRAPHY AS REFERENCE Jing-Houng Wang, Yi-Hao Yen, Kuo-Chin Chang, Yuan-Hung Kuo, Tsung-Hui Hu, Chien-Hung Chen Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

以瞬時肝彈性檢查為標準比較二維和 點剪波超音波肝彈性檢查對慢性 C 型 肝炎病患評估肝纖維化程度的效用 王景弘 顏毅豪 張國欽 郭垣宏 胡琮輝 陳建宏 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系 Background: For patients with chronic hepatitis C, this study aimed to compare the performances between two dimensional (2D) and point shearwave elastography (SWE) in assessing hepatic fibrosis.

Methods: Patients with chronic hepatitis C scheduled for liver ultrasonography (US) and transient elastography at the same morning was enrolled prospectively. In addition to liver US, 2D- and point-shear wave elastography (ElastQ, ElastPQ, EPIQ 7G, Philips, USA) were performed to determine liver stiffness. As the reference, transient elastography (TE, Fibroscan; Echosens, Paris, France) was performed to determine the fibrosis stage (F) by an experienced technician without knowledge of result of 2D- and pointSWE. Stratified by TE values, the F0-1 value was ＜7.5 kPa, F2 7.5-9.4 kPa, F3 9.5-12.5 and F4＞ 12.5 kPa. We compared the performances of 2Dand point-SWE in diagnosing various F stage with area under receiver operating curve (AUROC).

The cutoffs and their diagnostic validities were determined.

Results: Between 2018/4 to 2019/5, a total of 399 patients (male/female: 175/224, mean age:

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65.1 years) was enrolled. The correlations were 0.822, 0.828 and 0.850 between 2D SWE and TE, point SWE and TE, and 2D SWE and point SWE. While the median values were 5.8 for F01, 7.2 for F2, 8.7 for F3 and 12.4 kPa for F4 in 2D SWE, they were 5.1, 6.4, 7.2 and 10 kPa in point SWE (r=0.774, p＜0.001; r=0.719, p＜ 0.001). Assessing with AUROC, the performance of 2D SWE was significantly better than point SWE in diagnosing F ≥2 (0.891 vs 0.859, p=0.005) and F ≥3 (0.901 vs 0.872, p=0.021).

The cutoff of 2D SWE in diagnosing ≥F2, ≥F3 and F4 were 6.7, 8.0 and 10.3 kPa with sensitivity/ specificity 89.1/82.8%, 90.1/83% and 94.8/90.0% respectively.

Conclusions: For chronic hepatitis C patients, there were good correlations among 2D SWE, point SWE and TE. With TE as the reference, 2D SWE is superior to point SWE in diagnosing patients with more than significant or severe fibrosis.

P.061

INCREASING AGE AND NON-LIVER COMORBIDITIES IN CHRONIC HEPATITIS B PATIENTS IN TAIWAN: A NATIONWIDE POPULATIONBASED ANALYSIS Yao-Chun Hsu1,2, Hsiu J. Ho3, Mindie H. Nguyen4, Chun-Ying Wu3,5 School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan1 Department of Medical Research, Fu-Jen Catholic University Hospital, New Taipei, Taiwan2 Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan3 Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California4 Division of Gastroenterology and Hepatology, National Yang-Ming University, Taipei, Taiwan5 Background: Taiwan is endemic for chronic hepatitis B (CHB) with prevalence of 13% in the adult population.

Aims: The study aims to characterize the temporal changes in age and non-liver comorbidity burden between 2001 and 2011 among CHB patients in Taiwan.

Methods: This study analyzed Taiwan National Health Insurance Research Database (NHIRD) to identify adult (≥18 years) patients with CHB (at least one inpatient or two outpatient claims for a known diagnosis of CHB, using ICD-9CM codes and disease-specific medications).

Cross-sectional analyses in 2001, 2006, and 2011 were performed to compare the changes in demographics and non-liver comorbidities over the decade.

Results: A total of 102,158, 252,809, and 338,200 eligible patients were identified in 2001, 2006, and 2011, respectively. The proportions of male CHB patients decreased from 69.9% in 2001 to 67.0% in 2011 (p＜0.001). The median age significantly advanced from 44.5 in 2001, 47.8 in 2006, to 51.9 years in 2011 (p＜0.001). In 2011, the prevalence of diabetes mellitus (24.3%), hypertension (35.2%), dyslipidemia (11.2%), stroke (9.8%), heart failure (4.2%), malignancy (7.6%); all increased significantly from 2001 (Table 1). Furthermore, the prevalence of chronic

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kidney disease (4.2%) and bone fracture (13.3%) in 2011 also increased significantly from 2001.

Moreover, the proportion with exposure to aspirin, non-steroidal anti-inflammatory drug, proton pump inhibitor, and steroid also increased over time (Table 1).

Conclusions: Between 2001 and 2011, the Taiwanese CHB population have aged and presented with a higher non-liver comorbidity burden. These findings may inform the management of CHB in treatment selection and safety monitoring.

P.062

DIRECT-ACTING ANTIVIRALS IN EAST ASIAN HEPATITIS C PATIENTS: REAL-WORLD EXPERIENCE FROM THE REAL-C CONSORTIUM Chung-Feng Huang1, Etsuko Iio2, Dae Won Jun3, Eiichi Ogawa4, Hidenori Toyoda5, Yao-Chun Hsu6, Hiroaki Haga7, Shinji Iwane8, Masaru Enomoto9, Dong Hyun Lee10, Grace Wong11, Chen-Hua Liu12, Jun Hayashi13, Jae Yoon Jeong14, Hideyuki Nomura15, Seung Ha Park16, Makoto Nakamuta17, Chi-Ming Tai18, Jia-Horng Kao12, Mei-Hsuan Lee19, Leslie Kam20, Linda Henry20, Sally Tran20, Pei-Chien Tsai1, Ming-Lung Yu1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital1 Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan2 Department of Gastroenterology, Hanyang University, Seoul, South Korea3 Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan4 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan5 Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital6 Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan7 Liver Center, Saga University Hospital, Saga, Japan8 Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan9 Department of Gastroenterology, Good GangAn Hospital, Busan, Korea10 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong11 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan12 Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan13 Department of Internal Medicine, Hanyang

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University College of Medicine, Guri Hospital, Guri, South Korea14 The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan15 Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, South Korea16 Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan17 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan18 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan19 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA20

regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes.

Conclusions: In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well-tolerated across the region.

Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Background: One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited.

Aims: This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia.

Methods: Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea and Hong Kong were recruited in the REAL-C registry, an observational chart review registry.

The primary outcome was sustained virologic response (SVR12, HCV RNA PCR＜25 IU/mL 12 weeks post-therapy).

Results: A total of 6,287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, P＜0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, P＜0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, P＜0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, P=0.21).

The SVR12 rate ranged from 91.1-99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across

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P.063

EFFICACY AND SAFETY OF PROPHYLACTIC USE OF TELBIVUDINE AND ENTECAVIR DURING CHEMOTHERAPY IN CHRONIC HEPATITIS B VIRUS INFECTION PATIENTS: A REALWORLD EXPERIENCE Ming-Yao Chen1, Jia-Horng Kao2,3, Chun-Jen Liu 2,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan1 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan2 Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan3

慢性 B 型肝炎病人在化療時使用喜必 福與貝樂克的功效與安全性：真實世 界的經驗 陳明堯1 高嘉宏2,3 劉俊人2,3 臺北醫學大學．部立雙和醫院消化內科1 國立臺灣大學醫學院臨床醫學研究所2 台大醫院內科部暨肝炎研究中心3 Background: Chemotherapy can cause Hepatitis B virus (HBV) reactivation, acute hepatitis, hepatic failure and even death. Preventive nucleot(s)ide therapy (NUCs) could reduce HBV flares during chemotherapy.

Aims: To evaluate the serial change of hepatitis B virus (HBV) DNA during chemotherapy in chronic HBV infection patients (CHB).

Methods: We collected 177 cancer patients with CHB from March 2009 to March 2014. NUCs were administrated 1 week prior to beginning chemotherapy, and lasted 6 months after the end of chemotherapy (per APASL guidelines 2012).

Serial HBV DNA was monitored.

Results: Of the 177 patients, 55.9% was male and mean age was 55.2 year-old. Fifty (n=88) patients took telbivudine (Sebivo, LdT), while 36% (n=64) took entecavir (Baraclude, ETV) for chemoprevention. Survival rate was 67% and 61% in LdT and ETV group respectively. Rate of

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HBeAg-positive was 7.8% (n=14). Baseline HBV DNA was 3.56 and 3.00 log IU/mL in LdT and ETV respectively. Fifty-one percent had baseline DNA which was less than 2000 IU/mL, while 49% was larger than 2000 IU/mL (10.5% was larger than a million IU/mL). HBV DNA was higher in positive than negative HBeAg (positive vs. negative=5.68 vs. 3.02 IU/mL). Patient was younger in positive HBeAg patients (positive vs. negative=41.7 vs.

56.3 year-old). Overall, HBV DNA reduction comparing with baseline at moth-6, month-12 and month-18 during chemotherapy was -3.05, -3.15 and -3.28 in LdT and -3.15, -3.52 and -3.53 in ETV respectively. In comparison of rate of HBV DNA negativety, rate at month-3, mon6, month-12 and moth-18 were 45.5, 66.7, 87.5 and 88.9 in LdT and 63.6, 71.4, 83.3 and 88.9 in ETV group. If the baseline DNA was higher, there was a trend of slower HBV DNA negativity.

If HBV DNA was still positive in month-3, DNA negativity rate in month-6, month-12 and month 18 was 42.9, 60 and 66.7% in LdT group. HBV DNA negativity rate of month-18 in LdT group was 80% if HBV DNA was detectable in month-6 and 91.7% if undetectable DNA at month-6. Of the 11 patient who had the DNA 6-moth after cessation of NUCs, 10 (88.9%) had reappearance of viral load.

Conclusions: NUCs was quit effective in HBV reduction during chemotherapy. There was no obvious different between LdT and ETV. We had to pay attention to the viral relapse after cessation of NUCs after chemotherapy.

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P.064

PROJECTION OF LONG-TERM BONE AND RENAL OUTCOMES USING TENOFOVIR ALAFENAMIDE (TAF) FOR THE MANAGEMENT OF CHRONIC HEPATITIS B (CHB) IN CHINA Ying Han1, Bin Wu2, Ming Hu3, Fengqin Hou4, Yida Yang5, Lei Wang6 Xijing Hospital of the 4th Military Medical University, Xiâ&#x20AC;&#x2122;an, China1 Renji Hospital of Shanghai Jiaotong University, Shanghai, China2 Huaxi Healthcare Policy and Pharmacoeconomics Research Centre, Sichuan University, Chengdu, China3 The 1st Hospital of Peking University, Beijing, China4 The 1st Affiliated Hospital of Zhejiang University, Hangzhou, China5 The 2nd Hospital of Shandong University, Jinan, China6

Results: Over a lifetime, TAF-treated patients were expected to have fewer events of CKDIII and ESRD (Table 1). Specifically, compared to TDF/ETV, TAF resulted in reductions of 51%/25% on CKDIII events, respectively. TAF patients had a lower lifetime rate of non-traumatic fractures, but experienced more events due to increased life expectancy.

Conclusions: Driven by its improved efficacy & safety profile, TAF is projected to reduce bone and renal complications compared to TDF and ETV.

Background: Treatments goals are to suppress viral replication and achieve normalization of alanine aminotransferase (ALT) levels to avoid liver damage and related liver complications; however, CHB treatments can increase risk of bone and renal adverse events.

Aims: In this study, we simulated the long-term bone and renal consequences of nuecleos(t) ide analog therapies on 100,000 Chinese CHB patients comparing TAF to tenofovir disoproxil fumarate (TDF) and entecavir (ETV).

Methods: The lifetime health outcomes model used an individual patient simulation framework.

Risk of Stage 3 chronic kidney disease (CKDIII) and end-stage renal disease (ESRD) were based on treatment-specific changes on estimated glomerular filtration rates (eGFR). Risk of nontraumatic fracture was based on applying treatment-speciďŹ c fracture risks (TAF hazard ratio vs. TDF: 0.956 from trials; ETV equivalent to TAF) to 10-year fracture rates from the Fracture Risk Assessment Tool algorithm. Life expectancy was influenced by treatment efficacy-related impacts on liver disease progression. Model inputs were sourced from randomized controlled trials and peer-reviewed Chinese literature and validated by Chinese hepatologists.

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P.065

THREE YEAR EFFICACY AND SAFETY OF TENOFOVIR ALAFENAMIDE (TAF) COMPARED TO TENOFOVIR DISOPROXIL FUMARATE (TDF) IN HBEAGNEGATIVE AND HBEAG-POSITIVE PATIENTS WITH CHRONIC HEPATITIS B: A SUB-ANALYSIS OF PATIENTS ENROLLED IN TAIWAN Wan-Long Chuang1, Henry Lik Yuen Chan2, Jia-Horng Kao3, Young-Suk Lim4, Ting-Tsung Chang5, Wai Kay Walter Seto6, Chi-Yi Chen7, Harry L.A. Janssen8, Owen Tsang9, Sien-Sing Yang10, Cheng-Yuan Peng11, Won Young Tak12, Vithika Suri13, John F. Flaherty13, Lanjia Lin13, Gregory Camus13, Anuj Gaggar13, Calvin Q. Pan14, Tzong-Hsi Lee15, Maria Buti16 Kaohsiung Medical University, Kaohsiung, Taiwan1 Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong2 National Taiwan University College of Medicine and Hospital, Taipei, Taiwan3 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea4 Department of Internal Medicine, Cheng Kung University Hospital, Tainan, Taiwan5 Queen Mary Hospital, Hong Kong6 Chia-Yi Christian Hospital, Chiayi, Taiwan7 Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada8 Princess Margaret Hospital, Hong Kong9 Cathay General Hospital, Taipei, Taiwan10 China Medical University Hospital, Taichung, Taiwan11 Kyungpook National University School of Medicine, Daegu, South Korea12 Gilead Sciences, Inc., Foster City, CA13 NYU Langone Medical Center, New York, NY14 Far Eastern Memorial Hospital, New Taipei, Taiwan15 Vall d’Hebron Barcelona Campus Hospitalari, Barcelona, Spain16 Background: In 2 identically-designed doubleblind, randomized (2:1), Phase 3 studies, TAF has shown efficacy non-inferior to that of TDF at

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Weeks 48 and 96, with a superior renal and bone safety profile.

Aims: Here we evaluated the comparative safety and efficacy of TAF and TDF in overall and patients from Taiwan who received these agents for 3 years.

Methods: 1298 patients (425 HBeAg-negative and 873 HBeAg-positive) with CHB were randomized and treated with TAF 25 mg QD or TDF 300 mg QD. Included in this analysis, were 1118 patients (759 HBeAg-positive and 359 HBeAg-negative; 93 patients were from Taiwan); 866 (76 Taiwan patients) of whom received TAF (both DB and OL) and 252 (17 Taiwan patients) who were treated with DB TDF for 3 years.

Efficacy analyses were performed by study and included virologic, biochemical, and serologic responses, while safety assessments including changes in hip and spine bone mineral density (BMD), and changes in serum creatinine and estimated GFR by Cockcroft- Gault method (eGFRCG) were performed in a pooled fashion.

Results: Baseline characteristics were similar between groups in overall and Taiwan populations receiving TAF and TDF. Rates of virologic control (HBV DNA＜29 IU/mL) were similar at week 144 in TAF vs. TDF patients enrolled from Taiwan in each study; a greater proportion of TAF vs TDF patients achieved ALT normalization at Year 3.

Overall, adverse events (AEs) and serious AEs were similar between groups. In regard to key bone and renal safety parameters, patients from Taiwan receiving TAF had smaller decreases in bone mineral density than those receiving TDF in the hip (mean change -1.044% vs. – 4.004%) and lumbar spine (mean % change – 0.315% vs. – 3.740%), as well as a smaller change in estimated glomerular filtration rate by CockcroftGault method (mean change – 0.9 vs. – 8.8).

Conclusions: After three years of treatment, patients including those from Taiwan achieved high and similar rates of virologic suppression were achieved and maintained with TAF compared with TDF treatment and continued improvements in renal and bone safety were observed in patients receiving TAF relative to those on TDF. The efficacy and safety results at Week 144 in HBeAg-negative and HBeAgpositive subjects from Taiwan are consistent with those of the overall population.

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P.066

BONE AND RENAL SAFETY ARE IMPROVED IN CHRONIC HBV PATIENTS 1 YEAR AFTER SWITCHING TO TENOFOVIR ALAFENAMIDE (TAF) FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) – A SUBANALYSIS OF PATIENTS ENROLLED IN TAIWAN Jia-Horng Kao1, Wai Kay Seto 2, Maria Buti3, Namiki Izumi 4, Young-Suk Lim5, Ting-Tsung Chang6, Chi-Yi Chen7, Sien-Sing Yang 8, Fehmi Tabak9, Cheng-Yuan Peng10, Vithika Suri11, John F. Flaherty11, Audrey Lau11, Anuj Gaggar11, Shuyuan Mo11, Abhijit Chowdhury12, Scott Fung13, Wan-Long Chuang14, Ed Gane15 National Taiwan University College of Medicine and Hospital, Taipei, Taiwan1 Queen Mary Hospital, Hong Kong2 Hospital Universitari Vall d’Hebron, Barcelona, Spain3 Japanese Red Cross Musashino Hospital, Tokyo, Japan4 Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea5 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan6 Chia-Yi Christian Hospital, Chiayi, Taiwan7 Cathay General Hospital, Taipei, Taiwan8 Cerrahpaşa Tıp Fakültesi, İstanbul Üniversitesi‒Cerrahpaşa, Istanbul, Turkey9 China Medical University, Taichung, Taiwan10 Gilead Sciences, Inc, Foster City, California, USA11 Institute of Post Graduate Medical Education and Research, Kolkata, India12 Toronto Center for Liver Disease, University of Toronto, Ontario, Canada13 Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan14 Auckland City Hospital, Auckland, New Zealand15 Background: TAF has shown efficacy non-inferior to that of TDF at Week 96 with less bone and renal

effects. Following implementation of a protocol amendment to extend double blind (DB) treatment for an additional year, 50% of patients were able to continue on DB treatment while the remainder had already rolled-over to open-label (OL) TAF at Week 96.

Aims: Here we compared the efficacy and safety from Week 96 to 144 in patients randomized to TDF in whom treatment was either continued or switched to TAF at Week 96. A sub-analysis of patients enrolled from Taiwan was performed.

Methods: In 2 identically-designed studies, 1298 HBeAg-negative and HBeAg-positive CHB patients (873 TAF, 425 TDF) were randomized and treated. In the TDF group, 211 (14 patients were enrolled from Taiwan) remained on TDF (DB TDF) while 180 (27 patients were enrolled from Taiwan) patients were switched to OL TAF (TDF → TAF) at Week 96. Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients from Week 96 to Week 144.

Results: Patient characteristics were similar for those who continued TDF and those switched to TAF. In the TDF → TAF group, improvements in eGFRCG were observed in overall and Taiwan populations, while those remaining on DB TDF showed a continued decrease in eGFRCG at Week 144. Similarly, significant improvements in hip and spine BMD were seen over 1 year in TDF → TAF patients while those remaining on TDF either had continued BMD declines or smaller increases. High rates of virologic suppression (HBV DNA＜29 IU/mL) were maintained in both groups of Taiwan patients (TDF → TAF 96.3% and DB TDF 92.8%), while a greater rate of ALT normalization (by 2018 AASLD criteria) was seen in TDF → TAF Taiwan patients at 1 year following switch (57.1% vs 85.2%).

Conclusions: Virologic control was maintained and ALT normalization was increased following switch from TDF to TAF. However, compared to those remaining on TDF for an additional year, patients switched to TAF had improved bone and renal safety. The results of patients enrolled from Taiwan are consistent with those of the overall population.

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P.067

RELIABILITY OF TRANSIENT ELASTOGRAPHY USING FIBROSCAN® IN EXPERIENCED AND INEXPERIENCED OPERATORS Li-Sha Wu, Po-Ke Hsu, Pei-Yuan Su, Yu-Chun Hsu, Cheng-Da Yang, Wei-Wen Su Division of Gastroenterology, Department of Internal Medicine Changhua Christian Hospital, Changhua, Taiwan

肝臟纖維化掃描於有無經驗操作者的 可靠度探討 伍麗莎 許柏格 蘇培元 徐有春 楊承達 蘇維文 彰化基督教醫院肝膽胃腸科 B a c k g r o u n d : Tr a n s i e n t e l a s t o g r a p h y (Fibroscan ®) is a FDA approved non-invasive procedure to do liver stiffness measurement (LSM) and steatosis. This non-invasive test is done by ultrasound based controlled attenuation parameter (CAP). CAP score distinguishes liver steatosis as S0 (＜248 dB/m), S1 (≥248 dB/ m), S2 (≥268 dB/m), S3 (≥280 dB/m). Since January 1, 2019, We use this method to examine cases of chronic hepatitis B and patients with type C infection and even fatty liver for steatosis stage. According to some journals (Karlas et al., 2017), we consider that there will be operator differences when operating this instrument, so we analyze whether experienced and inexperienced operators have different CAP scores.

Aims: See if there is any difference between experienced and inexperienced operators using fibroscan.

Methods: We retrospectively and randomly collected 42 patients in 3 months since January 1, 2019. These 42 patients simultaneously perform transient elastography on experienced (labeled as Lisa) and inexperienced (just having training license and labeled as Peiyi) (Figure 1) operators in two separate room. Each patient recorded CAP (dB/m) and kPa value. Use pearson correlation and T test to check whether the reports are related.

Results: The average patient’s transient elastograph report showed in Lisa versus Peiyi as fibrosis result: 12.0 ± 2.3 kPa versus 11.5±2.0 (mean ± SD) and steatosis result: 253±8.9 dB/ m versus 248.1 dB/m (mean ± SD). Experienced

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(Lias) and inexperienced group (Peiyi) has significant correlation either fibrosis: r=0.984, p＜ 0.001 or steatosis: r=0.862, p＜0.001.

C o n c l u s i o n s : Tr a n s i e n t e l a s t o g r a p h y (Fibroscan®) is a simple and accurate method to measure liver fibrosis or steatosis. In this study, with or without experience, Transient elastography reports are still credible as long as trained technicians are trained.

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P.068

SUSTAINED VIROLOGICAL RESPONSE TO PEGYLATED INTERFERON PLUS RIBAVIRIN THERAPY DOES NOT DECREASE THE INCIDENCE OF SYSTEMIC LUPUS ERYTHEMATOSUS OR RHEUMATOID ARTHRITIS IN PATIENTS WITH CHRONIC HEPATITIS C Wei-Fan Hsu1,2, Pei-Chien Tsai3,4, Hsueh-Chou Lai1,5, Chi-Yi Chen6, Kuo-Chih Tseng7, Hsing-Tao Kuo8, Chao-Hung Hung9, Shui-Yi Tung9, Jing-Houng Wang10, Jyh-Jou Chen11, Pei-Lun Lee11, Rong-Nan Chien12, Chun-Yen Lin12, Chi-Chieh Yang13, Gin-Ho Lo14, Chi-Ming Tai14, Chih-Wen Lin14, Jia-Horng Kao15,16, Chun-Jen Liu15,16, Chen-Hua Liu15,16, Sheng-Lei Yan17, Ming-Jong Bair18, Wei-Wen Su19, Cheng-Hsin Chu20, Chih-Jen Chen20, Ching-Chu Lo21, Pin-Nan Cheng22, Yen-Cheng Chiu22, Chia-Chi Wang23, Jin-Shiung Cheng24, Wei-Lun Tsai24, Han-Chieh Lin25, Yi-Hsiang Huang25, Ming-Lung Yu3,4, Cheng-Yuan Peng1,26, T-COACH Study Group Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan2 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3 School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan4 School of Chinese Medicine, China Medical University, Taichung, Taiwan5 Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan6 Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan7

Division of Hepato-gastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan8 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan9 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan10 Division of Gastroenterology and Hepatology, Liouying Chi-Mei Hospital, Tainan, Taiwan11 Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan12 Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan13 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan14 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan15 Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan16 Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan17 Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan18 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan19 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan20 Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan21 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital; College of Medicine, National Cheng Kung University, 201

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Tainan, Taiwan22 Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, New Taipei City, Taiwan23 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan24 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan25 School of Medicine, China Medical University, Taichung, Taiwan26

干擾素治療的持續病毒學反應不會減 少慢性 C 型肝炎患者全身性紅斑狼瘡 或類風濕性關節炎的發生率 許偉帆1,2 蔡佩倩3,4 賴學洲1,5 陳啟益6 曾國枝7 郭行道8 洪肇宏9 董水義9 王景弘10 陳志州11 李佩倫11 簡榮南12 林俊彥12 楊基滐13 羅錦河14 戴啟明14 林志文14 高嘉宏15,16 劉俊人15,16 劉振驊15,16 顏聖烈17 白明忠18 蘇維文19 朱正心20 陳志仁20 羅清池21 鄭斌男22 邱彥程22 王嘉齊23 鄭錦翔24 蔡維綸24 林漢傑25 黃怡翔25 余明隆3,4 彭成元1,26 T-COACH Study Group 中國醫藥大學附設醫院消化系內科1 中國醫藥大學生物醫學研究所2 高雄醫學大學附設醫院肝膽內科與肝病中心3 高雄醫學大學癌症研究中心4 中國醫藥大學中醫系5 嘉義基督醫院內科部6 大林慈濟醫院內科部7 奇美醫院內科部8 嘉義長庚紀念醫院胃腸肝膽科9 高雄長庚紀念醫院胃腸肝膽科10 柳營奇美醫院胃腸肝膽科11 林口長庚紀念醫院胃腸肝膽科系12 秀傳紀念醫院胃腸肝膽科13 義大醫院胃腸肝膽科14 國立臺灣大學醫學院臨床醫學研究所15 台大醫院胃腸肝膽科16 彰濱秀傳紀念醫院胃腸肝膽科17 台東馬偕紀念醫院胃腸肝膽科18 彰化基督教醫院胃腸肝膽科19 馬偕紀念醫院胃腸肝膽科20 天主教聖馬爾定醫院腸胃肝膽科21 成大醫院胃腸肝膽科22 台北慈濟醫院肝膽胃腸科23

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高雄榮民總醫院胃腸肝膽科24 臺北榮民總醫院胃腸肝膽科25 中國醫藥大學醫學系26 Background: Chronic hepatitis C (CHC) is well known for its extrahepatic manifestations, including diabetes mellitus, mixed cryoglobulinemia, systemic lupus erythematosus, arthritis, and sicca syndrome. Approximately 40– 74% of CHC patients experience immunological complications during the course of the disease. A previous study showed that pegylated interferon plus ribavirin (PR) therapy decreased the cumulative incidences of renal and cardiovascular outcomes, including end-stage renal disease, ischemic stroke, and acute coronary syndrome.

Another study further revealed that successful hepatitis C virus (HCV) eradication in patients with diabetes mellitus (DM) decreased the incidence of clinical outcomes related to DM. However, the impacts of baseline characteristics, virological profiles, and therapeutic outcome on autoimmune diseases are largely unknown.

Aims: To elucidate the effects of the baseline factors and sustained virologic response (SVR) to PR therapy on autoimmune diseases in CHC patients through this multi-center cohort study.

Methods: Taiwanese Chronic Hepatitis C Cohort (T-COACH) is a nationwide cooperative HCV registry cohort from 23 regional hospitals and medical centers in Taiwan between 2003 and 2014. 12,770 CHC patients who received PR therapy for at least 4 weeks were enrolled in this retrospective study. Baseline demographic and virological features and therapeutic response to PR were recorded. The diagnoses of autoimmune diseases and death were ascertained by specific codes of the International classification of Disease, Ninth revision, Clinical Modification (ICD-9-CM) once at admission or more than three times at the outpatient clinic connecting to Taiwan National Health Insurance Research Database (NHIRD), and Death Registry, respectively.

Univariate and multivariate Cox proportional hazard regression analyses with age- and sexadjustments and death as a competing risk, and various subgroup analyses were performed.

Results: Of 12,770 patients, 5,954 (46.6%) patients were male, and 1,969 (15.4%) patients had liver cirrhosis. The mean age was 54.6±11.4 years. The mean AST and ALT were 91.1±64.4 and 137.4±110.3 U/L, respectively, and mean

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FIB-4 was 2.9±2.5. 6,052 (47.4%), 5,811 (45.5%), and 907 (7.1%) patients had genotype 1, 2, and non-1/2 HCV infections, respectively, and the mean HCV RNA was 5.7±1.0 log10 IU/mL. 1,269 (10.0%) and 1,411 (11.1%) patients had DM and hypertension, respectively. The mean follow-up duration was 5.3±2.9 years with a total of 67,930 person-years, and the annual incidence of systematic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases, such as cryoglobulinemia, Sjögren’s syndrome, and lichen planus, were not assessable due to few events (n＜3). Only body mass index (BMI) ≥ 24 kg/m2 was an independent predictor of lower annual incidence of SLE and RA (hazard ratio=0.40, 95% confidence interval: 0.17–0.93, P=0.034) after adjustment for competing mortality. An SVR to PR was not associated with a lower incidence of SLE or RA in all subgroup analyses, stratified by age, sex, BMI, AST, ALT, FIB-4, DM, hypertension, liver cirrhosis, and HCV genotype.

Conclusions: CHC patients achieving SVR to PR therapy did not exhibit a lower annual incidence of SLE or RA compared to non-SVR patients.

Baseline BMI ≥ 24 kg/m2 was an independent predictor of lower incidence of SLE and RA in CHC patients.

P.069

THE REALITY OF GENOTYPE 4 HEPATITIS C INFECTION IN A REGIONAL HOSPITAL IN SOUTHERN TAIWAN Chien-Heng Shen1, Kao-Chi Chang1, Shui-Yi Tung1, Chih-Yi Lee2, Chao-Hung Hung1, Sheng-Nan Lu1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 Division of Laboratory Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan2

南臺灣某區域醫院基因型第四型 C 型 肝炎感染真實性 沈建亨1 張國基1 董水義1 李至益2 洪肇宏1 盧勝男1 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科1 長庚醫療財團法人嘉義長庚紀念醫院檢驗醫學科2 Background: Genotype (GT) 4 is a rare case in Taiwan as well as Asia.

Aims: To investigate the prevalence and treatment efficacy of GT4 HCV infected patients in Southern Taiwan.

Methods: From Jan 2017 to Dec 2018, all patients infected with chronic hepatitis C, who underwent the National Health Insurance (NHI)-reimbursed direct-acting antiviral agent (DAA) treatment, were retrospectively enrolled for analysis.

Results: A total of 1211 patients were enrolled in this study and the genotype distributions were GT1: 2 (0.17%), GT1a: 18 (1.49%), GT1b: 740 (61.1%), GT2: 400 (33.03%), GT2b: 1 (0.08%), GT3: 3 (0.25%), GT4: 4 (0.33%), GT6: 14 (1.16%), GT1a+1b+6: 8 (0.66%), GT1b+2: 11 (0.91%), and GT1b+6: 10 (0.83%), respectively. The overall SVR with per-protocol (PP) anaIysis was 96.8%.

All the four patients were diagnosed as GT4 in a commercial test, but were diagnosed as GT2 in another commercial test and also confirmed as GT2a by direct sequencing. Two of them were treated with 12-weeks Elbasvir/grazoprevir, and one achieved sustained virological response (SVR). The other two were treated with 12-weeks Ledipasvir/sofosbuvir, and both achieved SVR. Conclusions: There was no GT4 patients in our hospital. All previous reported cases of GT4 should be mistyped of GT2.

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P.070

NEW INSIGHTS INTO RISK FACTORS FOR SJOGREN SYNDROME IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: A NATIONWIDE POPULATION-BASED COHORT STUDY Ting-Chia Lin1, Chun-Hsiang Wang1, Lein-Ray Mo1, Kuo-Kuan Chang1, Ruey-Chang Lin1, Ming-Jeng Kuo1, Jen-Juan Kuo1, Keh-Cherng Wey1, Yu-Hon Lin1, Yuan-Chi Mao1, I-I Chen1, Yuan-Tsung Tseng2 Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan1 Comittee of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan2

C 型肝炎病人發生薛格連氏症候群相 關危險因子的新觀點：一個以全國人 口為對象之世代研究 林廷嘉1 王俊雄1 牟聯瑞1 張國寬1 林瑞昌1 郭明正1 郭振源1 魏克承1 林裕鴻1 毛元治1 陳一毅1 曾元聰2 台南市立醫院肝膽胃腸科1 台南市立醫院醫學研究委員會2 Background: Chronic hepatitis C virus (HCV) infection has been identified as a cause of Sicca symptoms (a known complication of Sjogren’s syndrome), one of immune-mediated extrahepatic manifestations (EHMs) which include renal disease, mixed cryoglobulinemia, arthritis, and sicca symptoms. Little is known about exact risk factors for developing Sjogren’s syndrome in HCV patients.

Aims: We designed a nationwide large-scale long-term study using registry data to examine above issue and clarify whether one EMH is a potential effect modifier of the other.

Methods: The data sourced for analysis in this study were retrieved from the Taiwan National Health Insurance (NHI) Research Database.

All diagnoses were coded according to the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM).

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We screened 16,743 HCV patients who were sampled from 3,000,000 insureds of the NHI program. We identified all HCV patients between January 1, 2000, and December 31, 2013. The observation period started from the index date to the end of 2013, or death, or the development of outcomes, whichever occurred first.

Results: Of 16,743 HCV patients, we excluded 4,431 patients who coexisted with other liver diseases. We classified the remaining 12312 patients into treated cohort (n=3769), who had received antiviral therapy with Peg-IFN plus ribavirin, and untreated cohort (n=8543). Pair matching of treated (n=3596) and untreated (n=3596) subjects were formed by propensity score matching (PSM) at a 1:1 ratio. 65 HCV patients (24 in treated cohort and 41 in untreated cohort) developed Sjogren’s syndrome during a mean follow-up period of 6 years. Based on multivariate Cox regression analyses of baseline factors and EHMs, antiviral treatment was associated with lower risks of Sjogren’s syndrome (HR, 0.56; 95% CI, 0.33-0.93; p=0.024). In reverse, the incidence of Sjogren’s syndrome was significantly higher in the presence of coronary artery disease (CAD) (HR, 1.77; 95% CI, 1.023.08; p=0.043), as compared with other EMHs. By the modified Kaplan–Meier method for analyzing between-group differences of 12-year cumulative incidences of Sjogren syndrome, treated patient without CAD were the least likely to develop Sjogren syndrome, compared to untreated patients with CAD (p=0.002).

Conclusions: We highlighted the existence of reciprocal interaction among EHMs. In our study, the relationship between CAD and Sjogren syndrome was not only a positive association but rather a causal linkage in HCV patients. Moreover, antiviral therapy is able to prevent against Sjogren syndrome. HCV patients, who had been suffering CAD and never received antiviral therapy, greatly increased likelihood of a Sjogren syndrome over the 12-year follow-up period.

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P.071

THE CLINICAL EFFICACY OF DIRECT ACTING ANTIVIRAL THERAPIES FOR PATIENTS WITH HCV AND HIV CO-INFECTION Tze-Sian Chan1, Tsong-Yih Ou2, Po-Jui Huang1, Wen-Sen Lee2, Chun-Nan Chen1, Gi-Shih Lien1, Ming-Shun Wu1 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan2

直接作用抗病毒藥物對 HCV 及 HIV 病 毒合併感染病人之臨床療效 張智翔1 歐聰億2 黃柏瑞1 李文生2 陳俊男1 連吉時1 吳明順1 臺北醫學大學市立萬芳醫院消化內科1 臺北醫學大學市立萬芳醫院感染科2

Glecaprevir/Pibrentasvir, and weeks 12 for other DAAs). They also received serum HCV RNA assessment at off-therapy week 12 to assess SVR12. Biochemistry parameters and other clinical parameters were analyzed.

Results: Of the 14 enrolled patients, 10 of them were male (71.43%). The genotype distribution of the cohort was 21, 28.57, 21, 28.57% for genotype Ia, Ib, 2a and 6a, respectively. Thirteen patients (82.86%) were treatment-naïve and none of them have cirrhosis. The overall VRET and SVR12 were 100% but the VR4 was 83% for protease inhibitors containing DAAs (Elbasvir/ Grazoprevir and Glecaprevir/Pibrentasvir) and 100% for protease inhibitor sparing DAAs (Ledipasvir/Sofosbuvir). Acute hepatitis developed in one patient receiving Elbasvir/Grazoprevir (7.14%) and acute herpes zoster occurred in one patient receiving Glecaprevir/Pibrentasvir (7.14%).

Conclusions: DAAs are safe and effective in HIV/HCV coinfected patients. Long-term follow up are required to assess the sustained efficacy.

Background: While the overall prognosis of HIV patients has greatly improved with the advent of highly active antiretroviral therapy (HAART), a small group of HIV patients, who has hepatitis C virus (HCV) coinfection remained at risk of succumbing to the disease. Approximately.

20-30% of HIV infected patients have HCV coinfection. Liver-related morbidity and mortality are one of the most feared complications of HIV infected patients, but they have limited access to liver transplantation. Treatment of HCV infection in HIV infected patients is highly necessary. Direct acting antiviral therapy has shown highly effective in the treatment of HCV infection. Newer DAAs have become available, but their effectiveness in HIV/HCV coinfection patients have not been reported before.

Aims: In the present study, we want to ask if DAAs is equally highly efficacious in patients with HIV infection in the real world. We also compare the effectiveness among different DAAs. Methods: Fourteen patients with HIV and HCV coinfection receiving DAAs were enrolled in this retrospective study. The patient characteristics were compared and the treatment-related complications were described. Patients received serum HCV RNA assessment at treatment weeks 4 (VR4) and end of therapy (VRET, weeks 8 for

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P.072

OUTCOMES OF OUTREACH CLINIC FOR HEPATITIS C VIRUS TREATMENT AT TOWNSHIPS OF YUNLIN COUNTY Chia-Chi Kuo1,2, Shih-Jer Hsu1,2, Min-Chin Chiu1,2, Jian-Jyun Yu1,2, Tsung-Hua Yang1,2, Yu-Jen Fang1,2, Ji-Yuh Lee1,2, Chien-Hung Chen1,2,3 Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan1 Hepatobiliary Medical Center, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

雲林縣 C 型肝炎外展門診治療成果 郭家旗1,2 徐士哲1,2 邱敏欽1,2 余健鈞1,2 楊宗樺1,2 方佑仁1,2 李基裕1,2 陳健弘1,2,3 台大醫院雲林分院內科部1 台大醫院雲林分院肝膽醫學中心2 台大醫院內科部3 Background: The patients with Hepatitis C virus (HCV) infection in hyperendemic townships of Yunlin County had several barriers for treatment.

To reach the WHO goal of eliminating HCV before 2030, we establish outreach clinic at the township public health center.

Aims: To investigate the seroprevalence and genotype distribution of HCV among the hyperendemic townships of Yunlin County and to overcome the barriers for HCV treatment.

Methods: We called back 143 patients with positive anti-HCV in two hyperendemic townships (Dapi and Yuanchang Township). All subjects received blood tests for further evaluation per requirements of National Health Insurance.

Advanced hepatic fibrosis (fibrosis stage F3) was assessed with fibrosis index based on 4 factors (FIB-4) test ≥3.25 or findings of ultrasonography.

Results: Among these 143 patients, the median age was 66 years. The overall HCV viremia rate was 68.5% (98/143). The median log10 HCV RNA level at baseline was 6.07 (2.78-7.27). The genotype (GT) distribution was GT 2, 60.2% (59/143), GT 1b, 30.61% (30/143), GT 1a, 1.02%

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(1/143), GT 1, 1.02% (1/143), and GT 6, 2.04% (2/143) respectively. There were five patients had mixed type genotype1b+2. Thirteen (9.1%) and 3 (2.1%) patients had advanced hepatic fibrosis (F3) and compensated cirrhosis, respectively.

Sixty (61.23%) patients received direct anti-viral agent (DAA) at out outpatient clinic. Twenty-six (26.53%) patients received DAA at other hospital.

Four (4.08%) patients received generic drug.

Five (5.1%) patients had no willing for therapy.

Two (2.04%) patients had experienced Interferon treatment. One (1.02%) patient refused due to old age and immobile. For those who had available HCV RNA at 12 weeks after DAA, the SVR12 rate was 97.5% (39/40).

Conclusions: The majority of chronic hepatitis C patients were willing to receive DAA treatment at the outreach clinic. The SVR rate was high and similar to those treated at major hospital.

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P.073

EFFECTIVENESS AND SAFETY OF DIRECT-ACTING ANTIVIRAL AGENTS FOR CHRONIC HEPATITIS C: A SINGLE-CENTER REALWORLD EXPERIENCE IN TAIWAN Yi-Ting Chou, Wei-Chen Huang, Jung-Chun Lin, Yu-Lueng Shih Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

elbasvir/grazoprevir, and 15 patients treated with Glecaprevir/Pibrentasvir were 100.0%, 93.1%, 100.0%, 100.0%, 88.5%, 100%, and 100.0%, respectively.

Conclusions: In conclusion, our study showed that the overall SVR12 rates in Taiwanese patients with CHC who received DAAs were similar with previous study. However, data related to other special subgroup including hemodialysis and organ transplantation are still insufficient.

More real-world data are still needed.

慢性 C 型肝炎使用直接作用抗病毒藥 物之有效性與安全性：台灣單一醫學 中心的使用經驗 周益霆 黃瑋琛 林榮鈞 施宇隆 三軍總醫院腸胃科 Background: Chronic hepatitis C (CHC) has a relative high prevalence at Taiwan estimated between 2% and 4%. Treatment with pegylated interferon (IFN) plus ribavirin result in about 50% of sustained virologic response. In the era of direct-acting antiviral agents (DAAs), many clinical trials have shown a well result of SVR. Also, there’s some real world data showed well response to DAA treatment in Taiwan. Here, we present a treatment experience of DAA in CHC in our hospital.

Aims: The aim of this study was to evaluate the effectiveness and safety of current DAA regimen in our hospital.

Methods: We performed a retrospective study on 266 CHC patients. The primary endpoint was undetectable HCV RNA (an HCV RNA level of＜ 15 IU/mL) at 12 weeks posttreatment (SVR12).

The results were stratified by different DAAs and HCV genotypes.

Results: Genotype 1b was the major genotype (175, 65.4%), followed by genotype 2 (72, 26.7%).

The patients were treated according to HCV genotype, clinical practice and reimbursement guidelines. The SVR12 rates of 87 treated with ledipasvir/sofosbuvir with or without ribavirin, 58 patients treated with sofosbuvir and ribavirin, 4 patients treated with sofosbuvir/daclatasvir, 58 treated with ombitasvir/paritaprevir/ritonavir/ dasabuvir with or without ribavirin, 35 treated with daclatasvir/asunaprevir, 9 patients treated with

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P.074

SUCCESSFUL ANTIVIRAL THERAPY DECREASED THE INCIDENCE OF EXTRA-HEPATIC MALIGNANCY AMONG CHRONIC HEPATITIS C PATIENTS: A REAL-WORLD NATIONWIDE STUDY ON TAIWANESE CHRONIC HEPATITIS C COHORT (T-COACH) Hsueh-Chou Lai1, Chung-Fen Huang2, Chi-Yi Chen3, Kuo-Chih Tseng4, Hsing-Tao Kuo5, Chao-Hung Hung6, Jing-Houng Wang7, Jyh-Jou Chen8, Pei-Lun Lee8, Rong-Nan Chien9, Chi-Chieh Yang10, Gin-Ho Lo11, Chi-Ming Tai11, Chih-Wen Lin11, Jia-Horng Kao12,13, Chun-Jen Liu12,13, Chen-Hua Liu12,13, Sheng-Lei Yan14, Ming-Jong Bair15, Chun-Yen Lin9, Wei-Wen Su16, Cheng-Hsin Chu17, Chih-Jen Chen17, Shui-Yi Tung6, Ming-Lung Yu2 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan3 Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan4 Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan5 Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung MemorialHospital, Chiayi, Taiwan6 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan7 Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan8 Division of Hepatology, Department of 208

Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan9 Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan10 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan11 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan12 Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan13 Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan14 Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan15 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan16 Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan17

成功的抗病毒治療降低了慢性 C 型 肝炎患者肝外惡性腫瘤的發生率：台 灣慢性 C 型肝炎全國性的世代研究 （T-COACH） 賴學洲1 黃釧峰2 陳啟益3 曾國枝4 郭行道5 洪肇宏6 王景弘7 陳志州8 李佩倫 8 簡榮南9 楊基滐10 羅錦河11 戴啟明11 林志文11 高嘉宏12,13 劉俊人12,13 劉振驊 12,13 顏聖烈14 白明忠15 林俊彥9 蘇維文16 朱正心17 陳志仁17 董水義6 余明隆2 中國醫藥大學附設醫院消化系內科1 高雄醫學大學暨附設醫院肝膽胰內科2 嘉義基督教醫院內科部3 大林慈濟醫院胃腸肝膽科4 奇美醫院肝膽胃腸科5 嘉義長庚紀念醫院肝膽胃腸科6 高雄長庚紀念醫院肝膽胃腸科7 柳營奇美醫院胃腸肝膽科8

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林口長庚紀念醫院消化系肝膽科9 彰化秀傳紀念醫院腸胃科10 義守大學胃腸肝膽科11 國立臺灣大學臨床醫學研究所12 台大醫院胃腸肝膽科13 彰濱秀傳紀念醫院胃腸科14 台東馬偕紀念醫院胃腸科15 彰化基督教醫院胃腸科16 台北馬偕紀念醫院胃腸科17 Background: Chronic hepatitis C virus (HCV) infection has correlated to both liver and nonliver cancers. HCV eradication reduced the risk of hepatocellular carcinoma (HCC). We aimed to explore the benefits of sustained virological response (SVR, defined as HCV RNA seronegativity throughout 24 weeks of postantiviral treatment follow-up) in reducing the risk of extrahepatic malignancy in a large realworld nation-wide Taiwanese Chronic Hepatitis C Cohort (T-COACH) from 21 medical centers or core regional hospitals, which encountered around 20% of treated population in Taiwan during 2003-2014.

Aims: We aimed to explore the benefits of sustained virological response (SVR, defined as HCV RNA seronegativity throughout 24 weeks of post-antiviral treatment follow-up) in reducing the risk of extrahepatic malignancy in a large realworld nation-wide Taiwanese Chronic Hepatitis C Cohort (T-COACH).

Methods: 12,282 chronic hepatitis C (CHC) patients who had received interferon-based therapy (9,363 SVR and 2,919 non-SVR) enrolled in T-COACH were linked to National Cancer Registry database for the development of extrahepatic malignancies, including those with potential associations and with the top-ranking incidence in Taiwan with a mean follow-up period of 4.32 years (maximum, 18 years).

Results: Three hundred and sixty-three (2.96 %) patients developed non-HCC malignancies over 54,209 person-years follow-up. The annual incidence of non-HCC malignancies did not differ between SVR and non-SVR patients (0.64% vs.

0.76%, respectively). 12 non-HCC malignancies with event of ≧ 3 cases were further analyzed.

Compared to SVR patients, non-SVR patients had a significant higher risk of gastric cancer (0.08% vs. 0.03% per person-year, respectively, P=0.016, figure 1A) and possessed borderline

risk of non-Hodgkin’s lymphoma (NHL) (0.06% vs. 0.03% per person-year, respectively, P=0.05, figure 1b) development. While considering death as a competing risk, cox hazard regression model revealed that independent factors associated with gastric cancer were non-SVR (Hazard ratio [HR]/ 95% confidence intervals [CI]: 2.46/1.08-5.64, P=0.03) and age (HR/CI: 3.30/1.24-8.75, P=0.02); whereas age was the only factor independently associated with NHL (HR/CI: 5.37/1.62-17.79, P=0.006). Imperatively, rather than patients aged ＞65 years (HR/CI: 0.94/0.18-4.82, P=0.94), the benefit of SVR in reducing NHL was only noted in patients with age＜65 years (HR/CI: 3.70/1.1811.62, P=0.03).

Conclusions: Successful anti-HCV therapy reduced the risk of gastric cancer and was beneficial for risk reduction of NHL among younger CHC patients, indicating CHC patients should be treated as early as possible.

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P.075

SUCCESSFUL ANTIVIRAL THERAPY REDUCED RISK OF PSYCHIATRIC DISORDERS AMONG CHRONIC HEPATITIS C PATIENTS: A NATION-WIDE REAL WORLD STUDY OF TAIWANESE CHRONIC HEPATITIS C COHORT (T-COACH) Pei-Chien Tsai1,2, Chiao-Li Khale Ke3, Chi-Yi Chen4, Kuo-Chih Tseng5, Hsueh-Chou Lai6, Cheng-Yuan Peng6, Hsing-Tao Kuo7, Chao-Hung Hung8, Jing-Houng Wang9, Jyh-Jou Chen10, Rong-Nan Chien11, Chi-Chieh Yang12, Gin-Ho Lo13, Jia-Horng Kao14,15, Chun-Jen Liu14,15, Chen-Hua Liu14,15, Sheng-Lei Yan16, Ming-Jong Bair17, Chun-Yen Lin11, Wei-Wen Su18, Cheng-Hsin Chu19, Chih-Jen Chen19, Shui-Yi Tung8, Ching-Chu Lo20, TCOACH Study Group Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan2 Department of Psychiatry, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3 Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan4 Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan5 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan6 Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan7 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan8 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung 210

Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan9 Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan10 Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan11 Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan12 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan13 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan14 Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan15 Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan16 Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan17 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan18 Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan19 Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan20

慢性 C 肝成功治療減少精神疾病之發 生風險 蔡佩倩1,2 柯巧俐3 陳啟益4 曾國枝5 賴學洲6 彭成元6 郭行道7 洪肇宏8 王景弘9 陳志州10 簡榮南11 楊基滐12 羅錦河13 高嘉宏14,15 劉俊人14,15 劉振驊14,15 顏聖烈16 白明忠17 林俊彥11 蘇維文18 朱正心19 陳志仁19 董水義8 羅清池20 TCOACH 研究團隊

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高雄醫學大學附設醫院肝膽胰內科1 高雄醫學大學附設醫健康管理中心2 高雄市立小港醫院精神科3 嘉義基督教醫院一般內科4 大林慈濟醫院胃腸肝膽科5 中國醫藥大學附設醫院消化系內科6 奇美醫院肝膽胃腸科7 嘉義長庚紀念醫院肝膽胃腸科8 高雄長庚紀念醫院肝膽胃腸科9 柳營奇美醫院胃腸肝膽科10 林口長庚紀念醫院消化系肝膽科11 彰化秀傳紀念醫院腸胃科12 義大醫院胃腸肝膽科13 國立臺灣大學臨床醫學研究所14 台大醫院胃腸肝膽科15 彰濱秀傳紀念醫院胃腸科16 台東馬偕紀念醫院胃腸科17 彰化基督教醫院胃腸科18 台北馬偕紀念醫院胃腸科19 天主教聖馬爾定醫院內科部20 Background: Chronic hepatitis C virus (HCV) infection is not only a liver disease but also a systemic disease. Chronic hepatitis C (CHC) patients are at higher risk of major psychiatric disorders; by contrast, interferon-based therapy for CHC may have psychiatric sequelae.

Aims: The current study aimed to evaluate the long-term outcome of major psychiatric disorders after interferon-based therapy in a nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH).

Methods: The T-COACH consisted of 15,836 CHC patients with age＞20 years, CHC＞ 6 months and interferon-based therapy for＞ 4 weeks from 23 regional hospitals and medical centers between 2003 and 2014. T-COACH encountered 21% of CHC-treated population in Taiwan during the 12-year period. After excluding patients without sustained virological response (SVR, undetectable HCV RNA 24 weeks after interferon therapy) available and patients positive for hepatitis B surface antigen, a total of 12,862 CHC patients were enrolled and linked to catastrophic illness and death databases of Taiwan National Health Insurance (NHI) for final analysis. Death before any major psychiatric disorders was considered a competing risk event. The incidence of newly diagnosed major psychiatric disorders, including affective

psychoses and schizophrenia, were compared between patients with and without achieving an SVR. Results: The annual incidence of major psychiatric disorders was 3.6 (2.4 for affective psychoses, 1.0 for schizophrenia and 0.2 for organic psychotic condition, respectively) per 10,000 person-years after interferon-based therapy. Female gender, younger age and mild fibrosis, but not SVR were factors associated with the risk of major psychiatric disorders in multivariate Cox-hazard model. However, the 5-year cumulative incidence rate of schizophrenia was significantly higher in non-SVR than in SVR patients (0.14% vs. 0.04%; p=0.036).

After age-, sex-adjusted, non-SVR patients had a significantly 5.9-fold higher risk for the development of schizophrenia compared with SVR patients. In particular, patients with age＜ 45 had a 3.95-fold and 14.78-fold risks of major psychiatric disorders (P=0.04) and schizophrenia (p=0.02), respectively, among non-SVR patients, compared to SVR patients.

Conclusions: Successful interferon-based therapy reduces the risks of major psychiatric disorders among younger population and schizophrenia among all age population of CHC.

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P.076

T-ACE OIL FOR VARICEAL EMBOLIZATION – SIMULATION EXPERIMENTS IN RATS Jui-Wen Kang, Chiung-Yu Chen, Xi-Zhang Lin Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan

大員油於靜脈瘤栓塞的應用—一個模 擬的動物實驗 康瑞文 陳炯瑜 林錫璋 成大醫院內科部胃腸肝膽科 Background: Acute variceal bleeding is a fatal complication in cirrhotic patient. Histoacryl mixed with Iodized oil (Currently, Lipiodol) is commonly used to treat cardiac variceal bleeding in Taiwan.

However, the price of current iodized oil is expensive.

Aims: We developed the new iodized oil, T-ACE oil, to increase market supply and conducted the animal study to simulate the process of injecting the mixture of iodized oil and Histoacryl to achieve venous embolization.

Methods: In first part of animal study, we injected mixture of T-ACE oil (0.25 ml) and Histoacryl (0.25 ml) into tail vein of 4 SD rats and lipiodol (0.25 ml) with Histoacryl (0.25 ml) into another 4 SD rats and measure the length of radiopaque retention in the tail vein. We also injected lipiodol (0.21 ml) with Histoacryl (0.29 ml) into another 4 SD rats. In the second part of study, we try to find the ideal mixing ratio for venous embolization. We injected the mixture of T-ACE oil and Histoacryl with different mixing ratio (1:1, 1:1.3, 1:2) into 4 SD rats in each group. The total injection volume was 0.3 ml in each rat. Then we repeated same method by injecting mixture of Lipiodol and Histoacryl. We measured the length of radiopaque retention in the tail vein and compared its length between groups.

Results: In the first part of animal study, under fluoroscopy, we can see the radiopaque deposition from tail vein to cavum pelvis. One rat died on second day and fluoroscopy showed some radiopaque deposition in the heart.

Therefore, in second part of animal study, we decrease the total injection volume from 0.5 to 0.3 ml to avoid fatal adverse event. Comparing

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the result of injecting the mixture of iodized oil and Histoacryl with different mixing ratio. The mean radiopaque length (mean±SD) of tail vein in T-ACE group was 98±16, 90±15, 81±4 mm in 1:1, 1:1.3: 1:2 mixing ratio respectively. The mean radiopaque length (mean±SD) of tail vein in Lipiodol group was 100±14, 92±14, 80±5 mm in 1:1, 1:1.3: 1:2 mixing ratio respectively.

Either in T-ACE oil or lipiodol group, 1:1 mixing ratio seems has longer length of radiopaque vein comparing than 1:1.3 or 1:2 mixing ratio. There is no significant different between T-ACE and Lipiodol group.

Conclusions: Comparing with lipiodol, T-ACE oil has similar characteristics in mixture injection with Histoacryl. Higher Histoacryl ratio will shorten the extent of venous embolization, which is consistent with the current experience of liquid embolization in interventional radiology.

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P.077

THE EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR IN CHRONIC HEPATITIS C PATIENTS Chia-Yen Dai1,2, Chung-Feng Huang1,2, Ming-Lun Yeh1,2, Ching-I Huang1,2, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

The baseline mean Cr and eGFR levels were 1.71±2.47 mg/dL and 80.4±37.3. The EOT and EOF levels were 1.84±2.68 and 79.2±37.9, and 2.02±2.79 and 75.0±38.4 (p for trend was 0.394 and 0.376, respectively). For the 53 patients with completed EOF data, the eGFR was 71.7±35.6, 71.9±35.9 and 74.5±38.7 at baseline, EOT and EOF, respectively p for trend was 0.695). No severe adverse effect was noted.

Conclusions: In the present real-world data, G/P had good effectiveness and safety profile.

艾百樂治療慢性 C 型肝炎成效 戴嘉言1,2 黃釧鋒1,2 葉明倫1,2 黃駿逸1,2 黃志富1,2 莊萬龍1,2 余明隆1,2 高雄醫學大學附設醫院內科1 高雄醫學大學醫學院內科2 Background: The pan-genotypic regimen glecaprevir/pibrentasvir (G/P) has been reimbursed by the Taiwan National Health Insurance since 2018 August in Taiwan. The higher sustained virological response (SVR) rate have been observed in clinical trials and real-world reports. The response in Taiwanese patients remained unknown.

Aims: The aim of the study is to evaluate the SVR rate in CHC patients treated with G/P in southern Taiwan.

Methods: We enrolled 247 patients (187, 58 and 12 patients treated for 8, 12 and 16 weeks, male: 126, mean age: 59.9±13.5 years) with compensated liver disease who were treated with G/P. The clinical data and lab data were collected.

The effectiveness (sustained virologic response 12 weeks after end-of-treatment, SVR12) was evaluated. For the safety evaluation, serial data of the AST, ALT and Cr with eGFR were collected and calculated.

Results: With total 57 patients (25, 30, 2 for 8, 12 and 16 weeks) reaches the end of follow up who can evaluated the SVR12. The virological response was 92.9, 98.4 and 100% at week 4, end-of-treatment and SVR12, respectively.

The baseline mean AST and ALT levels were 55.3±41.9 and 65.1±59.6 u/L and the level were 26.4±11.3 and 22.1±15.8 at EOT, 28.5±9.5 and 22.1±15.6 at EOF. For the renal function,

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P.078

EVOLUTION OF THE SEROPREVALENCE OF VIRAL HEPATITIS IN UREMIC PATIENTS ON HEMODIALYSIS Yu-Ju Wei1, Chung-Feng Huang1,2, Yi-Hung Lin1, Ming-Lun Yeh1,2, Wen-Yi Lin1, Ching-I Huang1, Po-Cheng Liang1, Chia-Yen Dai1,2, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

透析患者病毒性肝炎的流行病學變化 魏鈺儒1 黃釧峰1,2 林宜竑1 葉明倫1,2 林文一1 黃駿逸1 梁博程1 戴嘉言1,2 黃志富1,2 莊萬龍1,2 余明隆1,2 高雄醫學大學附設醫院內科部肝膽內科1 高雄醫學大學醫學院內科2 Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) were leading causes of chronic liver disease in dialysis patients which was associated with high mortality and morbidity. The treatment uptake of HCV may be underappreciated in the population despite interferon free therapy available. The evolution of seroprevalence and treatment rate of viral hepatitis in the special population is elusive.

Aims: We aimed to elucidate the evolution of seroprevalence and treatment rate of viral hepatitis in the special population.

Methods: The Formosan Coalition for the study of Liver Disease in Chronic Kidney Disease (FORMOSA-LIKE group) performed two mass screens among uremia patients on regular hemodialysis in 2012 (n=1680) and 2019 (n=2326), respectively. All subjects were tested for HBV and HCV serology and virology. Four hundred and ninety patients who stayed in both screens were evaluated for the sequential change of viral hepatitis markers.

Results: The seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV antibody (Ab)

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and both HBsAg/anti-HCV Ab seropoitivity was (13.63% vs. 11.5%, P=0.046), (17.3% vs. 13.6%, P=0.002) and (2.44% vs. 1.66%, P=0.084) in 2012 and 2019, respectively. Among the 290 anti-HCV seropositive patients in 2012, two hundred and nine (72.1%) patients had persistent viremia, 78 (26.9%) patients had spontaneous HCV clearance, whereas only 3 (1.03%) patients received interferon-based therapy. In 2019, one hundred and seventy-seven (56.0%) of the 316 patients with anti-HCV seropositivity had HCV viremia at the time of surveillance.

Among patients without HCV viremia, 91 (28.8%) patients had spontaneous HCV seroclearance, and 48 (15.2%) patients achieved sustained virological response by antivirals (interferonbased regimens [n=8], directly acting antivirals [DAAs, n=40]). Of the 490 uremic patients who received sequential screen both in 2012 and 2019, twelve (21.8%) of the fifty five HCV-viremia patients received anti-HCV treatment, six patients had new anti-HCV seropositivity (0.24%/year; 5 patients with persistent viremia and 1 patient with spontaneous HCV clearance) and 2 had new HBsAg seropositivity (0.07%/year), whereas 3 patients (0.1%/year) and 7 patients (0.23%/year) experienced anti-HCV and HBs loss, respectively.

Conclusions: The treatment uptake of HCV is underutilized in uremic patients even when DAAs are widely available. Efforts should be made to facilitate the anti-HCV treatment in the highly contagious population.

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P.079

ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN NONALCOHOLIC FATTY LIVER DISEASE IN MICE Jung-Chun Lin1, Yi-Jen Peng2, Hsuan-Hwai Lin1, Tien-Yu Huang1, Yu-Lueng Shih1, Tsai-Yuan Hsieh1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan2

P.080

ANALYSIS OF ANTIBIOTIC PROPHYLAXIS IN THE PREVENTION OF REBLEEDING IN CHILD-PUGH CLASS A CIRRHOTIC PATIENTS WITH ACUTE VARICEAL HEMORRHAGE Min-Chin Chiu1, Chieh-Chang Chen1,2, Chien-Hung Chen1,2, Chun-Jen Liu2, Hsiu-Po Wang2, Ming-Shiang Wu2 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2

林榮鈞1 彭奕仁2 林煊淮1 黃天祐1 施宇隆1 謝財源1

Child-Pugh A 肝硬化病人於急性靜脈 瘤出血時使用預防性抗生素以減少再 出血之分析

三軍總醫院內科部胃腸肝膽科1 三軍總醫院病理部2

邱敏欽1 陳介章1,2 陳健弘1,2 劉俊人2 王秀伯2 吳明賢2

Background: Nonalcoholic steatohepatitis (NASH) is an inflammatory lipotoxic disorder, but how sympathetic nervous system (SNS) is involved and activated within the liver is still unclear. We previously reported that SNS plays an important role in carbon tetrachloride-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical or drug-induced hepatotoxicity and circulating immune response.

Aims: In the present study, we sought to determine the SNS involved in the inflammatory response in murine NASH. Methods: C57BL/6J mice with or without chemical sympathectomy were fed chow or methionine-choline deficient (MCD) diet.

Results: Compared to the control mice fed an MCD diet, sympathectomized mice fed an MCD diet had significantly attenuated liver inflammation and injury. Chemical sympathectomy reduced NASH-induced endoglin, HGF, and MCP-1. Our results suggest that sympathectomized mice are protected against diet-induced NASH. Conclusions: SNS-associated inflammation appears to be the key player in the chemokinemediated sterile inflammatory response in murine NASH.

台大醫院雲林分院內科部1 台大醫院內科部2

交感神經系統在小鼠非酒精性脂肪性 肝病中的角色

Background: Gastroesophageal variceal bleeding is one of the most common and serious complications in cirrhosis. The existing data shows that infection has negative influence on hemostasis in cirrhotic patients. Due to immunocompromised and bacterial translocation, cirrhotic patients have high risks of infection when suffering from gastrointestinal bleeding.

Antimicrobial agents are of proved efficacy to prevent infection and rebleeding after variceal hemorrhage, especially in decompensated cirrhosis. However, the discussions and reports about Child-Pugh (CP) class A are still lacking.

We thus conducted a retrospective study to analyze the relationship between prophylactic antibiotics and rebleeding and infection during acute variceal hemorrhage.

Aims: To analyze whether antibiotic prophylaxis prevents rebleeding and infection in CP class A cirrhotic patients with acute variceal hemorrhage.

Methods: In this retrospective study, we reviewed the endoscopic reports and medical records from National Taiwan University Main Hospital and Yun-Lin Branch. Individuals with CP class A cirrhosis, age above 20 years and

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endoscopically confirmed acute variceal bleeding were enrolled into the study. The exclusion criteria were pregnancies, vital organ failures, prior cerebrovascular accidents, non-liver related malignancies, active antiplatelet or anticoagulant agents use, antibiotic exposure within two weeks before bleeding episode and confirmed infection before endoscopic study. CP class A cirrhotic patients with more poor prognostic factors (ascites and frequent hepatic encephalopathy at baseline condition) were also excluded.

Results: Our study totally recruited 884 CP class A cirrhotic patients with acute variceal hemorrhage. Among these patients, there were 511 cases with antibiotic prophylaxis while 373 without and the overall five-day rebleeding rate was 1%, six-week rebleeding rate was 13% and infection rate was 13%. After logistic regression analysis of relevant variables, antimicrobial prophylaxis had significant correlation with endoscopic treatment (OR: 2.2593, 95% CI: 1.4438 to 3.5354), identified bleeder (OR: 1.7250, 95% CI: 1.1913 to 2.4978), hepatocellular carcinoma (OR: 1.6449, 95% CI: 1.2096 to 2.2370) and heart rate (OR: 1.0146, 95% CI: 1.0073 to 1.0219). After propensity score matching, the rates of five-day rebleeding, sixweek rebleeding and infection showed no significant difference between patients with antimicrobial prophylaxis and those without.

Conclusions: For acute variceal hemorrhage, antibiotic prophylaxis shows no significant effects on prevention of rebleeding or infection in CP class A cirrhosis.

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P.081

REAL-WORLD EFFECTIVENESS AND SAFETY OF GLECAPREVIR/ PIBRENTASVIR (GP) FOR THE TREATMENT OF CHRONIC HEPATITIS C INFECTION: DATA FROM THE CGMH EXPERIENCE Kuo-Chin Chang1, Chun-Yen Lin2, Chien-Hung Chen1, Sheng-Nan Lu1,3, Chao-Hung Hung1,3, I-Shyan Sheen2, Rong-Nan Chien2, Chih-Lang Lin4, Tsung-Hui Hu1 Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan3 Keelung Chang Gung Memorial Hospital, Keelung, Taiwan4

用 Glecaprevir/Pibrentasvir（GP） 治療慢性 C 型肝炎之真實有效性與安 全性：長庚醫院之經驗 張國欽1 林俊彥2 陳建宏1 盧勝男1,3 洪肇宏1,3 沈一嫻2 簡榮南2 林志郎4 胡琮輝1 高雄長庚紀念醫院1 林口長庚紀念醫院2 嘉義長庚紀念醫院3 基隆長庚紀念醫院4 Background: Glecaprevir/pibrentasvir (GP) is a pangenotypic direct-acting antiviral regimen approved for treating adults chronically infected with hepatitis C virus (HCV). There are limited real-world data on GP to date. To evaluate the effectiveness and safety of GP under real-world conditions in the Chang Gung Memorial Hospital.

Aims: This retrospective cohort study included 247 patients treated with GP from August to October 2018 that monitors patients with chronic HCV infection. Data were collected from patients who initiated GP. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Safety and tolerability were also assessed.

Methods: This retrospective cohort study included 247 patients treated with GP from August to October 2018 that monitors patients

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with chronic HCV infection. Data were collected from patients who initiated GP. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12).

Safety and tolerability were also assessed.

Results: As of 30 June 2019, 247 patients received GP and had documented SVR12 data, treatment and discontinuation. At baseline, the patients were infected with HCV genotype 1 (13%), G2 (73%), G3-6 (8%) and mixed type (6%), HCV treatment-naïve (92%), with cirrhosis (54%), and treated for12 weeks (54%). The overall SVR rates were 99%, patients were treated 8-week, 12 or 16-week: 98%, 100% and 100%, respectively. Treatment in age＞ 65 y/o patients, female gender, high BMI (＞ 30), high FIB-4 level, and low eGFR level (＜30) had a 98.9%, 100%, 100%, 100% and 100%, respectively, SVR12 rate with 12 or 16 week G/ P. There was two documented virological failure (relapse). Overall, 0.4 % (1/247) elevated AST ＞5x UNL and 2.83% (7/247) elevated bilirubin (T) level＞3x UNL. The renal function was not significant elevation in renal function before and after GP treatment.

Conclusions: Glecaprevir/pibrentasvir was highly effective and well tolerated under real-world conditions.

P.082

PREOPERATIVE ALBI GRADE PREDICTS THE OUTCOMES IN NON-B NON-C HCC PATIENTS UNDERGOING PRIMARY CURATIVE RESECTION Fai-Meng Sou1, Chih-Che Lin2, Chih-Chi Wang2, Tsung-Hui Hu1, Chien-Hung Chen1, Ming-Chao Tsai1,3 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan2 Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan3

術前 ALBI 在非 B 型非 C 型肝炎患者 的肝癌經手術切除後預後的探討 蘇輝明1 林志哲2 王植熙2 胡琮輝1 陳建宏1 蔡明釗1,3 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 長庚醫療財團法人高雄長庚紀念醫院肝臟移植中 心及一般外科暨長庚大學醫學系2 長庚大學臨床醫學研究所3 Background: Although most HCC is related to viral infection, there is a substantial population of HCC patients (10-15%) who are negative for both markers of HBV and HCV infection (non-B, non-C) in Taiwan and the incidence of NBNCHCC has recently tended to increase.

Aims: To assess the prognostic factors in non-B non-C HCC patients after primary resection.

Methods: This retrospective study enrolled 220 non-B non-C HCC patients who underwent primary surgical resection from 2008/01/01 to 2016/01/15 at Kaohsiung Chang Gung Memorial Hospital. The predictive factors for recurrencefree survival (RFS) and overall survival (OS) were analyzed.

Results: After a median follow-up of 54.5 months, 97 patients (44.1%) had HCCs recurrence and 59

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patients (29.4%) died. The overall survival rate in 1-year, 3-year, and 5-year were 82%, 76%, and 71% respectively. The disease-free survival rate in 1-year, 3-year, and 5-year were 65%, 56%, and 48% respectively. ALBI grade 2 and 3 (p=0.007), tumor recurrence (p=0.017), FIB-4 (p=0.004), and vascular invasion (p=0.045) are related to poor overall survival. In subgroup analysis, patients with ALBI grade 2 and 3 had significant poor OS (p=0.017) compared with ALBI grade 1.

Conclusions: In non-B non-C HCC patients after curative resection, the ALBI grade is a useful prognostic index to predict the overall survival

P.083

SIGNIFICANT CHANGES OF LIPID PROFILE BUT NOT INSULIN RESISTANCE AFTER ACHIEVING SVR IN CHRONIC HEPATITIS C PATENTS TREATED WITH IFN-FREE DAAS Ya-Ting Cheng, Wen-Juei Jeng, Yen-Chun Liu, Yi-Chung Hsieh, Wei Teng, Yi-Cheng Chen, Rong-Nan Chien, Chun-Yen Lin, I-Shyan Sheen Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

台灣慢性 C 型肝炎病患經口服抗病毒 藥物治癒後脂質而非醣質代謝會出現 變化 鄭雅婷 鄭文睿 劉彥君 謝彞中 滕威 陳益程 簡榮南 林俊彥 沈一嫻 林口長庚紀念醫院胃腸肝膽科 Background: Hepatitis C virus infection altered metabolism including cholesterol synthesis, hepatic steatosis and insulin resistance (IR).

In interferon-based (IFN) era, the presence of insulin resistance (IR) is an unfavorable factor for sustained viral response (SVR). However, in those treated with IFN-based and achieved SVR, significantly decreased insulin resistance but increased cholesterol, LDL and triglyceride level was observed. Since IR is no more a factor for SVR in patients treated with DAA, the lipid profile and insulin resistance after DAA treated remain uncertain.

Aims: This study aims to clarify the metabolic profile changes in CHC patients received DAA treatment.

Methods: CHC patients who had received complete IFN-free DAAs treatment and achieved SVR In Chang Gung Memorial Hospital, Linkou Medical Center with available metabolic profiles including HbA1c, sugar AC, insulin, HOMA-IR, total cholesterol, high-density lipoprotein (HDL), LDL and triglyceride at baseline, end-of-treatment, SVR12 and SVR24 were recruited. Paired test were performed for these metabolic profile’s changes before and after DAA treatment.

Results: A total of 433 CHC patients, mean

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age of 63.8, 40.6% male, 339 genotype 1 (GT1) and 96 non-GT1, were analyzed. Comparing to baseline, increased HbA1c level (6.06-＞6.0＞6.17-＞6.15, P＜0.001) but not HOMA-IR (3.23-＞3.28-＞3.55-＞3.02, P=0.15) was noted.

However, all lipid profile including cholesterol (169 ＞178-＞183-＞181, P＜0.001), TG (100-＞107＞110-＞111, P=0.001), HDL (48-＞49-＞51-＞52, P＜0.001) and LDL (100-＞108-＞109-＞108, P ＜0.001) level were significantly increased after DAA treatment. This phenomenon exists in both GT1 and non-GT1 CHC patients.

Conclusions: Successful eradication of HCV with IFN-free DAA regimen resulted in significant changes of lipid profile but no impact on the insulin resistance.

P.084

EFFICACY AND SAFETY OF NIVOLUMAB TREATMENT IN ADVANCED HEPATOCELLULAR CARCINOMA: RESULTS FROM A REAL-WORLD COHORT Hsueh-Chou Lai1,2, Po-Heng Chuang1,3, Cheng-Kuo Chen4, Cheng-Yuan Peng1,3, Wen-Pang Su1,3, Guan-Tarn Huang1,3, Jaw-Town Lin1,3 Division of Hepato-gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 School of Chinese Medicine, China Medical University, Taichung, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 Division of Hepato-gastroenterolog Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan4

Nivolumab 治療晚期肝細胞癌的療效 和安全性：真實世界的報告 賴學洲1,2 莊伯恒1,3 陳政國4 彭成元1,3 蘇文邦1,3 黃冠棠1,3 林肇堂1,3 中國醫藥大學附設醫院消化系內科1 中國醫藥大學中醫學院中醫學系2 中國醫藥大學醫學裕醫學系3 亞洲大學附設醫院肝膽腸胃科4 Background: Nivolumab, an immune check point inhibitor, have presented a favorable result in advanced hepatocellular carcinoma patients with sorafenib-experienced based on reports from CheckMate 040 (NCT01658878). Patients with advanced hepatocellular carcinoma (HCC) have reimbursement for sorafenib since august 2012, while nivolumab has not reimbursement until June 2019. Real-world data on efficacy and safety of nivolumab is limit.

Aims: To evaluate the efficacy and safety of nivolumab in a real-world setting.

Methods: We reviewed retrospectively medical records of patients with advanced HCC (confirmed by radiologic definition and/or biopsy) in China Medical University Hospital and Asia Medical University Hospital. Those patients have been treated with nivolumab from October 2018 to April 2019. We excluded patients who

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received with duration of nivolumab less than 2 months. We analyzed data regarding the baseline demography of patients, stages of tumor, cirrhosis state, adverse effects of nivolumab treatment, objective repose and disease control rate.

Results: A total of 29 patients out of Forty-one advanced HCC patients who were treated with longer than two months duration of nivolumab were enrolled in this study duration. Among all 29 patients who had cirrhosis, there were 18 patients Child-Turcotte-Pugh (CTP) class A, 8 patients CTP B, and 3 patients CTP C. 87% of them had Barcelona stage C HCC at time of initial treatment of nivolumab. 23 of 29 patients had experienced tyrosine kinase inhibitor treatment. The overall objective response rated (ORR) was 21 % and disease controlled rated (DCR) was 55%. CTP class A, class B, and class C have ORR 22%, 25%, and 0%. These classes’ DCR were 67%, 50%, and 0%, respectively. Overall, 27 (82%) of 29 patient had any degree adverse events.

One patient who achieved complete response with three months treatment nivolumab duration developed fulminant hepatitis and died after three weeks cessation of nivolumb.

Conclusions: The results have similar ORR and DCR with CheckMate 040 (NCT01658878).

Severe adverse events of patients with advanced HCC who received nivolumab may develop at any times and should be monitored closely.

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P.085

CLINICAL CHARACTERISTICS IN NONOBESE PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE Yi-Chung Hsieh1, Wei Teng1, Wen-Juei Jeng1, Shiu-Feng Huang2, Chun-Yen Lin1, I-Shyan Sheen1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan2

非酒精性脂肪肝在非肥胖病人的臨床 特徵 謝彞中1 滕威1 鄭文睿1 黃秀芬2 林俊彥1 沈一嫻1 林口長庚紀念醫院胃腸肝膽科系1 國家衛生研究院分子與基因醫學研究所2 Background: Nonalcoholic fatty liver disease (NAFLD) has been the most common etiology of chronic liver disease worldwide and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Obesity and metabolic syndrome were usually observed in these patients. However, a small proportion of NAFLD patients had normal body mass index (BMI), so-called nonobese or lean NAFLD. Clinical characteristics of patients with nonobese NAFLD in Taiwan have not yet been well described.

Aims: To investigate clinical characteristics in patients diagnosed with nonobese NAFLD. Methods: Patients with biopsy-proven NAFLD in Chang Gung Memorial Hospital, Linkou Medical center, between February 2014 and December 2017, were included. Those with viral, alcoholic, and autoimmune liver diseases were excluded.

The Asian BMI cutoff of 25 kg/m2 at the time of biopsy was used to define nonobese NAFLD. Clinical characteristics including age, gender, type 2 diabetes mellitus (DM), biochemistry, hemogram, and fibrosis status at the time of biopsy were analyzed compared between obese and nonobese NAFLD patients.

Results: One hundred and fifty-six NAFLD patients were analyzed and 87 (55.8%) had NASH. Nonobese NAFLD was diagnosed in

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54 (34.6%) patients, of whom 34 (63%) had NASH presentation. The NAFLD activity score in nonobese ones was 5 (2-7). The mean age was 49.7±11.5 years old, and 28 (51.9%) were male. Nine (19.1%), nine (18%), and 5 (9.4%) patients had DM, hypertension, and liver cirrhosis, respectively. Baseline biochemistry and hemogram showed ALT was 108.5 (23-562) U/ L, total bilirubin was 0.8 (0.2-3.6) mg/dL, albumin was 4.6 (2.5-5.1) g/dL, ALP was 80 (41-291) U/ L, r-GT was 71.5 (15-1881) U/L, platelet was 222.5 (67-395) 103/µL, total/HDL/LDL cholesterol were 198.4±41.0/46 (3-73)/120.3±33.3 mg/dL, triglyceride was 135 (47-510) mg/dL, and uric acid was 5.8±1.8 mg/dL. Noninvasive scores exhibited AST/ALT ratio (AAR) was 0.6 (0.2-4.6), AST to Platelet Ratio Index (APRI) was 0.3 (0.13.5), and the Fibrosis-4 (FIB-4) score was 1.3 (0.2-11). Comparing obese and nonobese NAFLD patients, there were no significant differences in clinical characteristics. By the multivariate logistic regression analysis, r-GT (adjusted OR: 0.997, 95% CI: 0.994-0.999) and AAR (adjusted OR: 4.0, 95% CI: 1.2-13.4) were independently associated with higher risks of nonobese NAFLD. Conclusions: About 35% of NAFLD patients are nonobese. These nonobese NAFLD patients had similar proportion of NASH presentation, type 2 DM, hypertension, lipid profile, and fibrosis status as comparing with obese NAFLD ones. Serum r-GT and AAR were risk factors of nonobese NAFLD.

P.086

REAL-WORLD EVIDENCES OF 12-WEEK LDV/SOF IN GT2 HCV PATIENTS IN TAIWAN – DATA FROM KAOHSIUNG CGMH Po-Lin Tseng, Jing-Houng Wang, Kwong-Ming Kee, Chien-Hung Chen, Yi-Hao Yen, Tsung-Hui Hu Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

慢性 C 型肝炎基因 2 型病患，使用 SOF/LDV 治療之成效報告—高雄長庚 經驗 曾柏霖 王景弘 紀廣明 陳建宏 顏毅豪 胡琮輝 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系 Background: LDV/SOF was approved for GT2 HCV infection from October, 2018 in Taiwan.

Although the efficacy and safety of LDV/SOF in HCV-2 patients were demonstrated in 3 clinical studies, the evidence from real-world is still limited. Here, we aim to determine the efficacy and safety of LDV/SOF in GT2 HCV patients in Taiwan real-world cohort.

Aims: NA Methods: Data of GT2 HCV patients receiving LDV/SOF from 2018/10~2019/06 in Kaohsiung CGMH were collected and retrospectively analyzed. The primary endpoint was SVR, defined as HCV RNA＜lower limit of quantification at follow-up week 12 (SVR12).

Results: In total, data from 335 GT2 patients receiving 12 weeks of LDV/SOF±RBV treatment were analyzed. Among them, 125 patients were male. The mean age of patients was 62.6 (years).

5 patients were mixed infection. There are 197 patients completed 12-week follow-up duration.

18 of them achieved SVR12. 186 patients achieved ETVR. Only 1 patient had no response, and 2 patients discontinued the treatment due to patient decision and poor compliance.

Conclusions: In our real-world evidences, 12week LDV/SOF±RBV treatment was effective and safe in GT2 mono-and mix-infected HCV patients. The efficacy did not differ from age, gender, and liver fibrosis stages.

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P.087

USEFULNESS OF SHEAR WAVE ELASTOGRAPHY IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE Keisuke Nakajima, Katsutoshi Sugimoto, Hirohito Takeuchi, Masakazu Abe, Yuu Yoshimasu, Yoshitaka Kasai, Yoshihiro Furuichi, Takao Itoi Tokyo Medical University, Tokyo, Japan Background: Shear wave elastography (SWE) is validated in chronic hepatitis C and B; however, limited data are available in Non-Alcoholic Fatty Liver Disease (NAFLD).

Aims: This study is aimed to assess the accuracy and the efficacy of SWE for the detection of fibrosis in patients with NAFLD and to evaluate the effect of other histologic parameters on SWE measurement.

Methods: 71 patients with histologically proven NAFLD (mean age, 50.8 years±15.7) were examined. All patients underwent SWE (AixplorerTM; SuperSonic Imagine) and FIB4 index. SWE measurements were compared to the histologic features based on of NAFLD activity score (NAS) and FIB4 index.

Results: The area under the ROC curve (AUC) for the diagnosis of hepatic fibrosis stages 3 or higher was 0.821 (optimal cutoff value, 13.1 kPa; sensitivity, 62.5%; specificity, 57.4%) for SWE, as was 0.822 (optimal cutoff value, 1.41; sensitivity, 71.9%; specificity, 53.9%) for FIB4 index, respectively. Median liver stiffness values measured using SWE showed a stepwise increase with increasing hepatic fibrosis stage (P<0.001), inflammation score (P=0.018), and ballooning score (P<0.001), and showed a stepwise decrease with increase hepatic steatosis stage (P=0.046).

Conclusions: SWE is a promising imaging modality for assessing the presence or absence of advanced fibrosis in patients with NAFLD. The effect of steatosis on SWE measurements may be controversial.

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P.088

COMPARATIVE EFFICIENCY OF URSODEOXYCHOLIC ACID AND COMBINATION OF VITAMIN E AND VITAMIN C IN THE TREATMENT OF NON-DIABETIC NONALCOHOLIC STEATOHEPATITIS Gocha Barbakadze, Tatia Khachidze, Manana Jebashvili, Gela Sulaberidze, Koba Burnadze Tbilisi State Medical University, Georgia Enmedic Clinic, Tbilisi, Georgia Background: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which effective therapy is still lacking. Despite an important role of oxidative stress in the pathogenesis of NASH, antioxidant approaches have not been investigated sufficiently.

Aims: The aim of the study was to compare the efficacy of ursodeoxycholic acid (UDCA) versus vita- min E plus vitamin C in non-diabetic patients with nonalcoholic steatohepatitis.

Methods: Patients with elevated aminotransferase levels and drinking, less than 40g alcohol/week with NASH diagnose were randomly assigned to receive either UDCA 15 mg/per kg/day (group A) or vitamin E 800 mg/day plus vitamin C 500 mg/ day (group B) for 12 months and control group, which did not receive any medical treatment.

Lifestyle modification was advised to all groups.

The primary study end point was improvement in aminotransaminase levels, secondary end points were improvement in steatosis score and improvement in fibrosis score.

Results: 107 patients were included 35 in the group A, 52 in the group B and 20 in control group, 11 patients dropped out, non because of side effects. Baseline characteristics were not significantly different between groups.

After 12 months treatment with vitamin E plus C, as compared with UDCA, was associated with a significant reduction of mean alanine aminotransferase (ALT) levels. Similarly, there was significant reduction of both mean steatosis score and fibrosis score.

Conclusions: Vitamin E plus C combination is an effective, safe and inexpensive treatment option in patients with NASH and may be useful to reduce damage from oxidative stress and slow the process leading to cirrhosis.

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P.089

UNDERSTANDING THE DYNAMICS OF HUMAN LIVER REGENERATION IN HEALTH AND DISEASE Malcolm R. Alison Centre for Tumour Biology, Barts Cancer Institute, London, UK Background: In high turnover epithelial tissues such as the intestine, homeostatic cellular replacement is achieved via a pool of stem cells. By contrast, turnover in the normal human liver is slow and the location and necessity of liver stem cells has been questioned. Partial hepatectomy has demonstrated that new hepatocytes can be generated from pre-existing hepatocytes, without the requirement of a stem cell population. However, lineage tracing in chronic injury models supports the involvement of liver stem/progenitors. Further complexity has arisen from the demonstration of both periportal and pericentral neo-hepatocyte generation, as well as hepatocyte to biliary epithelial cell transdifferentiation (cell re-programming) and vice versa. This collective knowledge has largely amassed from rodent studies; by contrast far less is known regarding the dynamics of human liver turnover, particularly during normal homeostasis.

Aims: We have aimed at understanding the clonal dynamics of normal human liver utilizing novel techniques we have developed that are applicable to man.

Methods: We have explored hepatocyte dynamics in normal human liver by utilising a combination of methylation of non-expressed genes and mitochondrial DNA (mtDNA) mutations as a molecular clock and clonal expansion respectively.

R e s u l t s : S p a t i a l l y, w e s h o w t h a t c l o n a l hepatocyte expansions are more commonly periportal than pericentral. Furthermore, by lasercapture microdissection and mtDNA sequencing, we have demonstrated that hepatocytes and ductal epithelial cells have a common cell of origin. Using methylation status, an ancestral relationship was detected from periportal clonal hepatocytes, but not from pericentral ones. Lastly, using mtDNA next-generation sequencing, we have demonstrated that within clonal hepatocyte expansions, greater genetic diversity exists in pericentral hepatocytes than those located in the

same clonal patch periportally.

Conclusions: This is the first study to show the stem cell of origin of normal human liver hepatocytes in the bile duct and that they stream towards the hepatic veins. The periportal junction of biliary epithelium and hepatocytes has long been suspected as a location of liver stem/ progenitors, thus this study demonstrates their involvement in human liver homeostasis.

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P.090

AR-SENSITIZED SORAFENIB EFFICACY VIA ENRICHED EPCAM STEMNESS IN HEPATOCELLULAR CARCINOMA Wei-Min Chung1, Wen-Lung Ma1,3, Chun-Mien Chang4, Chun-Chieh Yeh6,7, Long-Bin Jeng6,7, Hsueh-Chou Lai2,5 Sex Hormone Research Center, Graduate Institute of BioMedical Sciences, and Graduate Institution of Cancer Biology, China Medical University, Taichung, Taiwan1 Section of Hepatobiliary, Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2 Department of Nursing, Asia University, Taichung, Taiwan3 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, 75390, USA4 School of Chinese Medicine, China Medical University, Taichung, Taiwan5 School of Medicine, China Medical University, Taichung, Taiwan6 Department of Surgery, China Medical University Hospital, Taichung, Taiwan7

在肝癌細胞中男性荷爾蒙受體會增加 EpCAM 癌幹細胞對雷沙瓦藥物之敏感 性 鍾偉敏1 馬文隆 1,3 張君銘4 葉俊傑 6,7 鄭隆賓 6,7 賴學洲2,5 中國醫藥大學性荷爾蒙中心1 中國醫藥大學附設醫院消化系肝膽科2 亞洲大學護理學系3 德克薩斯大學西南醫學中心內科部4 中國醫藥大學中醫學系5 中國醫藥大學醫學系6 中國醫藥大學附設醫院外科部7 Background: Androgen Receptor (AR) bimodal function has been discussed in Hepatocellular carcinoma (HCC) that promote initiation and suppress progression. However, the translational value of AR roles in HCC is unknown. Sorafenib, the multiple kinase inhibitor, is considered as the standard adjuvant therapy for unresectable HCC

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patients.

Aims: This study aimed to evaluate the impact of AR in Sorafenib intervention in HCC laboratory models.

Methods: AR cDNA was introduced in HCC cells to test AR function, cancer characteristics, and Sorafenib cytotoxic I.C.50. Knockout hepatic AR in carcinogen and HBV-induced HCC mouse models to examine AR effect on marker gene expressions. Quantitative PCR and immunoblot for testing AR effect on gene expressions.

Cell sorting with stemness surface antigens to examine Sorafenib effect in vitro and in vivo. At last, bioinformatics for associating AR or EPCAM expressions with prognosis.

Results: Using in vitro model, AR cDNA stable expressing cells exhibited excellent transactivation function, better colony and sphere forming activities, and facilitated tumorigenicity capacity compared to parental HCC cells. While examining stemness markers, EpCAM was dramatically increased upon AR expression. Consistently, EpCAM+ cells was significantly decreased in spontaneous HCC AR knockout HCCs, compared to that of wildtype littermates. AR also ablated Sorafenib downstream signals, e.g., ERK, AKT, and p38MAPK, while they were been upregulated in parental cells. As for Sorafenib cytotoxic effect, the AR expressing cells are vulnerable to treatments. Moreover, sorting EPCAM or CD133 from HCC sphere cells, the IC.50 of Sorafenib were drastically lowered in AR+/EPCAM+ compared to AR–/EPCAM–. Strikingly, Sorafenib IC.50 are similar between AR+/CD133+ vs.

AR–/CD133+ cells. Besides, Sorafenib regimen was robust suppress tumor growth in AR+/ EPCAM+, but not AR–/EPCAM– implanted cells.

At last, bioinformatics analysis revealed EPCAM is prognostic biomarkers in Asian and nonalcohol consumption HCC patients, suggesting a targeting value in those patients.

Conclusions: AR+/EPCAM+ could be therapeutic responsiveness marker for HCC patients receiving Sorafenib, particularly in Asian and non-alcohol related HCC. It’s important to conduct an prospective survey associating AR/ EPCAM expression to therapy outcomes.

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P.091

THE PREDICTED HUMAN C-TYPE LECTIN 18 LEVELS PATHWAY IN LIVER CANCER CELL LINE Tsung-Yu Tsai, Cheng-Yuan Peng Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

預測人類 C 型凝集素 18 在肝癌細胞株 的相關調控路徑 蔡宗佑 彭成元 中國醫藥大學附設醫院消化內科 Background: Hepatocellular carcinoma (HCC) was an important complication in HBV infection.

CLEC18 is a novel N-linked glycosylated protein which are highly expressed in liver. We previously demonstrated that liver C-type lectin 18 (CLEC18) level was down regulated in HCC tumor part compared to non-tumor part. We also found that lower CLEC18 ratio of tumor part/non-tumor part ( ＜1) had advance disease activity such as higher HBV DNA level and longer PT prolong compared to higher CLEC18 ratio (＞1). However, the possible mechanism of CLEC18 and HCC was unknown.

Aims: To search the possible mechanism of CLEC18 in hepatocarcinogenesis.

Methods: Database of JASPAR, Gene card and PROMO was used to predict the possible transcription factor of CLEC18 gene. We used HepG2 and Hu7 cell line to confirm the possible pathway which inducing CLEC18 expression.

Results: We had used database (JASPAR, Gene card and PROMO) to predict the possible transcription factor of CLEC18 gene. After we cross-refer these three different databases, we found that the STAT1, STAT2 and STAT5 were the most possible transcription binding site in CLEC18 gene. The cytokine which upstream regulates STAT1 and STAT5 is IL-6. We found that CLEC18 was up regulated after IL-6 stimulation in Hu7 cell line but not in HepG2 cell line.

Conclusions: We firstly found that CLEC18 is involved in STAT1, STAT5 downstream pathway.

We speculated that CLEC18 plays a critical role in JAK/STAT pathway and may related with liver hepatocarcinogenesis. Further studies will be going on.

P.092

THE INDOCYANINE GREEN RETENTION TEST AS A NON-INVASIVE MARKER OF ESOPHAGEAL VARICES IN PATIENTS WITH HEPATOCELLULAR CARCINOMA Hsiao-Sheng Lu1, Yi-Hsiang Huang1,3, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Institute of Clinical Medicine, National YangMing University School of Medicine, Taipei, Taiwan3

利用靛氰綠滯留測試檢測肝癌病患是 否合併食道靜脈區張 呂學聖1 黃怡翔1,3 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明大學醫學系2 國立陽明大學臨床醫學研究所3 Background: The indocyanine green 15-minute retention (ICG-r15) test was considered as a non-invasive marker of portal hypertension and esophageal varices (EV) in cirrhotic patients.

However, the performance of ICG-r15 in patients with hepatocellular carcinoma (HCC) was rarely assessed.

Aims: This study aimed to evaluate the value of ICG-r15 as a non-invasive marker of EV in patients with HCC. Methods: One hundred thirty-seven HCC patients with compensated liver function who received ICG-r15 test and endoscopy screening for EV were retrospectively enrolled during October 2007 to December 2018. The predictive value of the ICG-r15 test and other non-invasive markers were evaluated for the diagnosis of EV. Results: In the study cohort, 30 (21.9%) patients had EV. The AUROC for EV of ICG-r15 was 0.784 (95% CI: 0.686-0.881, -2 ln (L): 77.889, AIC: 79.889), which had best predictive value compared to other non-invasive markers. The cut-off value of ICG-r15 for rule in EV was 31.0% which had 40.0% sensitivity and 98.1% specificity,

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and the cut-off value for rule out EV was 9.5%, which had 86.7% sensitivity and 50.5% specificity.

In multivariate analysis, ICG-r15 (Odds ratio: 1.062, 1.014-1.114; p=0.015) and Park index (Odds ratio: 1.535, 1.091-2.159; p=0.014) were independently related to the presence of EV. Conclusions: ICG-r15 with cut-off values 9.5% for rule out and 31.0% for rule in EV, may be a practical non-invasive marker in patients with HCC.

P.093

ON-TREATMENT CHANGES IN FIB-4 AND ONE-YEAR FIB4 VALUES HELPS IDENTIFY CHRONIC HEPATITIS B PATIENTS RECEIVING ENTECAVIR THERAPY WITH THE LOWEST RISK OF HEPATOCELLULAR CARCINOMA Hung Wei Wang1, Chien-Hung Chen2, Hsueh-Chou Lai1, Tsung-Hui Hu2, Jing-Houng Wang2, Cheng-Yuan Peng1 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

治療中 FIB-4 的變化值與一年的 FIB-4 值可幫忙辨識接受貝樂克治療後具最 低肝癌發生風險之慢性 B 型肝炎病患 王鴻偉1 陳建宏2 賴學洲1 胡琮輝2 王景弘2 彭成元1 中國醫藥大學附設醫院內科部消化系1 高雄長庚紀念醫院內科部胃腸肝膽科系2 Background: Nucleos(t)ide analogues (NAs) have been widely used in patients with chronic hepatitis B (CHB). However, the incidence of hepatocellular carcinoma (HCC) is not eliminated despite with NA therapy. Noninvasive fibrosis indices can help stratify the risk of HCC in CHB patients receiving NA therapy.

Aims: We investigated the predictive performance of the on-treatment changes in FIB-4 and oneyear FIB-4 values for HCC risk in CHB patients receiving entecavir therapy.

Methods: We included 1325 NA-naïve CHB patients (noncirrhotic: 844; cirrhotic: 481) treated with entecavir from January 2007 to August 2012. Baseline patient characteristics, pre- and on-treatment (one-year) fibrosis indices were collected and analyzed to predict HCC risk by univariate and multivariate Cox regression analyses. We used Kaplan–Meier analysis to compare the cumulative HCC incidences among subgroups of patients exhibiting distinct patterns of on-treatment index changes and oneyear index values. △Index was defined as the

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difference between the index value at one year and that at baseline.

Results: In this cohort, the median age was 50±17 years, 72.7% were male and 36.3% were cirrhotic. During a median follow-up period of 4.1 years, 105 patients (7.9%) developed HCC. By multivariate Cox regression analysis, albumin, AFP 12M, APRI 12M (＞0.53 vs ≦0.53), FIB-4 12M (＞2.56 vs ≦2.56), and △FIB-4 (＞0 vs ≦0) were significant predictors of HCC in all patients.

In the non-cirrhotic subgroup, FIB-4 12M (＞ 1.58 vs ≦1.58) (hazard ratio [HR]: 12.10; 95% confidence interval [CI]: 1.531–95.60; P=0.018), and △FIB-4 (＞0 vs ≦0) (HR: 7.013; 95% CI: 1.874–26.24; P=0.004) were independent predictors of HCC. In the cirrhotic subgroup, albumin (HR: 0.564; 95% CI: 0.388–0.820; P=0.003), AFP 12M (HR: 1.009; 95% CI: 1.005– 1.012; P＜0.0001), FIB-4 12M (＞2.88 vs ≦2.88) (HR: 3.576; 95% CI: 2.147–5.956; P＜0.0001) and △FIB-4 (＞0 vs ≦0) (HR: 2.227; 95% CI: 1.465–3.385; P＜0.0001) were independent predictors of HCC by multivariate Cox regression analysis. A combination of △FIB-4 and FIB-4 12M stratified the cumulative risk of HCC into three subgroups in the non-cirrhotic and cirrhotic subgroups, respectively, with each P＜0.0001 by the log-rank test. (non-cirrhotic: high [n=88]: FIB-4 12M＞1.58/△FIB-4＞0 [HR: 40.35, 95% CI: 5.107–318.7, P＜0.0001]; low [n=459]: FIB-4 12M ≦1.58/△FIB-4 ≦0 [HR: 1 as reference] and cirrhotic: high [n=89]: FIB-4 12M＞2.88/△FIB-4 ＞0 [HR: 9.576, 95% CI: 5.033–18.22, P＜ 0.0001]; low [n=203]: FIB-4 12M ≦2.88/△FIB4 ≦0 [HR: 1 as reference]). Non-cirrhotic CHB patients treated with entecavir who achieved FIB4 12M ≦1.58 or FIB-4 12M＞1.58/△FIB-4≦0 exhibited the lowest 5-year HCC risk of 0.68%.

Cirrhotic CHB patients treated with entecavir who achieved FIB-4 12M＞2.88/△FIB-4＞0 exhibited the highest 5-year HCC risk of 42.9%.

Conclusions: On-treatment changes in FIB4 and one-year FIB-4 values helps identify CHB patients receiving entecavir therapy with the lowest risk of HCC.

P.094

THE EFFICACY OF DIFFERENT TREATMENTS IN HEPATOCELLULAR CARCINOMA PATIENTS WITH PORTAL VEIN THROMBOSIS Fei-Pang Kuo, Chao-Chuan Wu, Jiann-Hwa Chen, Chia-Chi Wang Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan

肝癌併肝門靜脈血栓的治療效果 郭飛鵬 伍超群 陳建華 王嘉齊 台北慈濟醫院肝膽胃腸科暨慈濟大學醫學院 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and one of the leading causes of cancer-related death worldwide. Portal vein thrombosis (PVT) can induce intrahepatic metastasis, deteriorate liver reserve and worsen the prognosis of HCC. Although systemic therapy is the gold standard of treatment, multi-modality treatment really exists in clinical practice. The efficacy of different treatment modalities for HCC patients with PVT remains unclear.

Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and one of the leading causes of cancer-related death worldwide. Portal vein thrombosis (PVT) can induce intrahepatic metastasis, deteriorate liver reserve and worsen the prognosis of HCC. Although systemic therapy is the gold standard of treatment, multi-modality treatment really exists in clinical practice. The efficacy of different treatment modalities for HCC patients with PVT remains unclear.

Methods: This is a retrospective study. The HCC patients (BCLC stage C) with PVT registered in Cancer center of Taipei Tzu-Chi Hospital since Jan. 2010 to Jan. 2016 were enrolled. PVT was categorized according to Vp classification.

The primary end-point is overall survival in differentmodalities of treatmentincluding surgical resection, nexavar, or local treatment such as radiotherapy, TACE etc.

Results: A total of 101 HCC (BCLC stage C) patients with PVT were included for final analysis.

The pathologic diagnosis of HCC is obtained in 43

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patients. According to Vp classification, there were 15, 11, 49, and 26 patients in Vp1, Vp2, Vp3, and Vp4 respectively. 30 patients received sorafenib treatment, but multi-modality treatment (more than 1 treatment method) in 37 patients. The median overall survival was significantly better in patients with branch PVT (BPV) than those with main PVT (MPV) (17.07 vs. 7.28 months, p＜0.001). The cumulative survival was better in HCC patients with PVT receiving treatment (vs. no treatment) or surgical resection (vs. no surgical resection), but no difference in term of TACE (vs. no TACE). The cumulative survival was similar between patients treated with sorafenib and those with other local treatments including surgical resection, radiation, or TACE etc.

Conclusions: The overall survival was better in HCC patients with PVT receiving surgical resection. The confounding factors included better liver reserve and lower frequency of main PVT in those treated with surgical resection.

However, TACE has no significant benefit on overall survival. The survival was similar between patients treated with sorafenib and those with other local treatments.

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THE IMPACT AND PREDICTORS OF RECURRENCE IN PATIENTS WITH EARLY OR VERY EARLY STAGE HEPATOCELLULAR CARCINOMA AFTER SURGICAL RESECTION Tzu-Hsuan Cheng, Wei-Chih Su, Jiann-Hwa Chen, Chia-Chi Wang Department of Gastroenterology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan

早期肝細胞癌經切除後的復發因素預 測及影響 鄭子軒 蘇偉志 陳建華 王嘉齊 台北慈濟醫院肝膽胃腸科暨慈濟大學醫學院 Background: Although surgical resection is a curative treatment for early hepatocellular carcinoma (HCC), the incidence of recurrence is still high due to background of chronic liver disease. The impact and factors associated with recurrence are unclear and deserve investigation.

Aims: Few system has been proposed to predict the prognosis for recurrent hepatocellular carcinoma (HCC), as being important determinants of survival: the stage of underlying liver disease, the different treatment modalities for HCC & prognosis was still unclear.

Methods: The HCC patients with BCLC stage 0 or A receiving surgical resection in Taipei TzuChi Hospital since Jan. 2009 to Jan. 2017 were enrolled retrospectively. The demographic, clinical and histological data were recorded. The primary endpoint was overall survival and recurrence.

Aggressive recurrence was defined as multiple recurrence, invasion to vessel or metastasis. The secondary endpoints were factors associated with HCC recurrence or aggressive recurrence.

Results: A total of 125 HCC patients (86 male; mean age 68.74±11.57 year-old) were included for final analysis. The survival rate was 96%, 91.2% and 89.6% at year 1, 3 and 5, respectively. During the follow-up period, 61 (48.8%) patients had HCC recurrence. Of them, aggressive recurrence was present in 16 (26.2%) patients. Based on cumulative survival curve, the HCC patients with recurrence had worse survival than those without recurrence (p=0.027).

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Among patients with recurrent HCC, the patients with aggressive recurrence had worse survival than those without (p=0.008). The only factor associated with HCC recurrence was multiple tumors (2 or 3 in number) at initial diagnosis, but not the tumor size or higher pathologic grade (Grade III and IV in differentiation). Positive HBsAg tends to have increased risk of recurrence (p=0.057). In contrast, positive anti-HCV seems to have a protective effect (p=0.06). No factor was identified to be associated with aggressive recurrence.

Conclusions: Early or very early stage HCC patients had satisfactory 5-year survival rate after surgical resection. However, the incidence of HCC recurrence was still high. The presence of recurrence or aggressive recurrence had bad impact on overall survival. The only predictor of HCC recurrence was multiple tumors, but not the tumor size or pathologic grade of differentiation.

P.096

TREATMENT FOR TACE POOR RESPONDED HEPATOCELLULAR CARCINOMA: EXPERIENCE IN A SINGLE TERTIARY MEDICAL CENTER Zong-Sian Cai1,2,3, Ching-Wei Chang1,2,3, Tsang-En Wang1,2,3, Ming-Jen Chen1,2,3, Cheng-Hsin Chu1,2,3 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan1 MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan2 MacKay Medical College, New Taipei, Taiwan3

經動脈栓塞治療反應不良肝癌之後續 治療處理—單一醫學中心臨床經驗 蔡宗憲1,2,3 張經緯1,2,3 王蒼恩1,2,3 陳銘仁1,2,3 朱正心1,2,3 台北馬偕紀念醫院內科部腸胃肝膽科1 馬偕醫護管理專科學校2 馬偕醫學院3 Background: Hepatocellular carinoma remains the third leading cause of cancer-related death worldwide. Although curative therapy such as radiofrequency ablation, surgical resection and liver transplantation can achieve 5-year survival rate more than 80%, most of the patients were diagnosed at later stage. Trans-arterial chemoembolization (TACE) is the standard treatment for those not amenable for currative therapy and without tumor distant metastasis or portal vein thrombosis. However, people with poor response for 2 times of TACE is common, and further treatment strategies remains controversial.

Aims: A retrospective cohort study for analysis the tumor response rate for patients had received 2 times of TACE with residual viable tumor who underwent further therapy.

Methods: From Sep. 2015 to May 2018, 70 patients had received more than 2 times of TACE, including those with HCC in intermediate stage or in early stage but not amenable for curative therapy. 35 patients were excluded because of exist of distant metastasis or PV thrombosis when complete 2 times of TAE/TACE, decompensated liver functions, interrupted by other loco-regional

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therapy such as ethanol injection, or loss follow up with no further cross sectional image to evaluate tumor response rate. Finally, 35 patients were included for analysis. We divided the patients into two cohorts for further study, including one kept ongoing TAE/TACE and the other received concurrent loco-regional therapy. Our primary outcome for efficacy analysis is overall tumor response rate (PR+CR) and disease control rate (PR+CR+SD) according to RECIST criteria.

Results: 19 patients kept ongoing multiple times of TAE/TACE (group 1) and 16 had combination therapy with loco-regional treatment (RAF or PEI) and TAE/TACE (group 2). Demographics data (Table 1) showed there is no statistic significant difference in terms of age, sex, BMI, viral hepatits, alcohols habit, liver cirrhosis, Child-Pugh score, mean size and numbers of tumor, and liver biochemistry. The overall response rate is mild higher in patients received combination therapy (50.0% vs 31.58%, p=0.268), and disease control rate is also mild higher in the combination therapy cohort (52.63% vs 37.5%, p=0.371), but both not reach the statistic significance.

Conclusions: TACE remains the single standard treatment for patients with intermediate stage HCC (BCLC stage B) or not amenable for curative therapy in many international guidelines.

However, for patients with poor or inadequate response for initial TACE, multiple disciplinary strategies were applied in the real world. Further studies were needed for prove the efficacy for these strategies.

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P.097

BENEFITS OF SNMC (STRONGER NEO-MINOPHAGEN C) FOR HEPTOMA PATIENT POST TRANSARTERIAL CHEMOEMBOLIZATION THERAPY Chi-Hsing Chen , Hsing-Tao Kuo, I-Che Feng, Yu-Min Lin, Ping-Hsin Hsieh, Ming-Jen Sheu Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

SNMC 可以減輕 TACE 的副作用 陳季杏 郭行道 馮意哲 林育民 謝秉欣 許銘仁 奇美醫院胃腸肝膽科 Background: Trans-arterial chemoembolization (TACE) is recommended for patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer (BCLC) staging system, because TACE was found to improve survival compared with the best supportive care in patients with unresectable HCC. However, the ischemic damages caused by TACE may lead to acute deterioration of hepatic function and is a potentially life-threatening complication.

A glycyrrhizin-containing product, Stronger Neo-Minophagen C (SNMC), containing Glycyrrhizinate monoammonium 2.65 mg, Glycine 20 mg and Cysteine 1mg per ml is widely used in Japan for suppression of hepatitis activity and for prevention of disease progression in patients with hepatitis B virus- and HCVinduced chronic hepatitis. Glycyrrhizin has been reported to mitigate hepatic inflammation by suppressing elevated ALT levels and preventing disease progression. The major side effects are hypokalemia and hypertension. The effect and side effect of SNMC on acute deterioration of hepatic function following TACE were still unknown.

Aims: This study aimed to evaluate the effect and side effect of SNMC on acute deterioration of hepatic function following TACE. Methods: This is a single-center, prospective, open-label, randomized, parallel study. Patients who fulfill the inclusion and exclusion criteria will be screened for eligibility. After screening, all patients will be recruited and randomized to one of the following treatment arms in a 1:1 ratio.

One arm of 30 patients will receive intravenous

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Stronger Neo-Minophagen C 100 mL (5 Amp) daily, begining on the day of TACE and continuous totally 3 days and the other arm of 30 patients without receive SNMC. The primary endpoint of our study was ALT and AST levels in the following 3 days of TACE. Secondary endpoints were Na+, K+, bilirubin total level, fever episode (BT ＞37℃ degree), hypertension, anorexia, during 3 days after TACE. Hypertension episode was defined as systolic blood pressure ≥160 mmHg, or with symptomatic hypertensive crisis under STAT anti-hypertension medication use. Anorexia was defined as below 2/3 amount of daily usual amount. Fever was numbered according to the ranges of degrees Celsius.

Results: Total 60 patients of intermediate BCLC stage HCC who received TACE were enrolled since April 2018. The baseline characters were comparable between the two groups. Within SNMC group, bilirubin total at day 3, PT INR and PT at day 3 were significant lower compared with control group (p=0.03, all). ALT and AST were elevated than baseline after the day of TACE procedure (day 0). Mostly, the levels of both transaminases reached the peak at the second day (day 2) after procedure, and subsided on the 3rd day (day 3) after procedure. But there was no significant difference between both groups.

Furthermore, fever episodes following for 3 days after TACE, and anorexia were noted significant difference between both groups (p=0.002, both).

Hypokalemia episode was no obvious difference between both groups. There was no hypertension episode or crisis or STAT medication use in both groups.

Conclusions: The patients with SNMC have favorable outcome in recovery from acute ischemic injury by TACE and they have less fever and anorexia. No significant hypokalemia and hypertension episode was noted. So we concluded that SNMC may be beneficial for patient receiving TACE treatment.

P.098

CLINICAL FEATURES OF HEPATOCELLULAR CARCINOMA IN NONALCOHOLIC FATTY LIVER DISEASE Bou-Zenn Lin1, Tsung-Jung Lin1, Chih-Lin Lin1, Li-Ying Liao1, Ting-An Chang2, Chin-Tsung Ting3, Kuan-Yang Chen1 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan1 Department of Pathology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan2 Department of Gastrointestinal Surgery, RenAi Branch, Taipei City Hospital, Taipei, Taiwan3

非酒精性脂肪肝病人的肝癌臨床表徵 林柏任1 林聰蓉1 林志陵1 廖麗瑛1 張廷安2 丁金聰3 陳冠仰1 臺北市立聯合醫院仁愛院區消化內科1 臺北市立聯合醫院仁愛院區病理科2 臺北市立聯合醫院仁愛院區消化外科3 Background: The main etiologies of hepatocellular carcinoma were often viral hepatitis B or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis (NASH), cirrhosis, and eventually hepatocellular carcinoma (HCC) in recent years.

NAFLD was strongly associated with obesity and metabolic syndrome.

Aims: This study was aimed to investigate the clinical features of HCC in NAFLD patients.

Methods: All HCC patients in NAFLD were recruited from the data base of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017. NAFLD was defined as non-viral hepatitis B, (either positive anti-HBs or negative anti-HBc), non-viral hepatitis C (negative antiHCV), noalcoholic (alcohol consumption less than 30 g/day) liver disease and if present or past histological or ulatrsonographic evidences of fatty liver.

Results: Eleven patients meeting the criteria were included from our database. Patient’s mean age was 64.1±14.3 years old, mean BMI was 27.2±4.2 kg/m2 and mean tumor size was 5.0±3.6 cm. The level of AFP more than 400 ng/ml was only found in one patient. Nine

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of them were men and two were women. Five of the patients had diabetes mellitus. Cirrhosis was observed in three patients, and one was confirmed by pathology and two by sonography.

Ten of the 11 cases were Child-Pugh classification A and one was classification B. One of the 11 patients was BCLC stage 0, 6 were BCLC stage A and 4 were BCLC stage B, none of them was BCLC stage C or D. Six of the patients received surgery, two received radiofrequency ablation and three received transarterial chemoembolization.

Conclusions: The HCC in NAFLD patients was diagnosed in an earlier stage and most of them could receive curative therapy. Most NAFLD patients with HCC were non-cirrhotic.

P.099

SORAFENIB WITH CONCURRENT MULTIPLE-LINE THERAPIES IMPROVES OVERALL SURVIVAL IN ADVANCED STAGE HEPATOCELLULAR CARCINOMA Pojen Hsiao1, Jen-Hao Yeh1,4, Gin-Ho Lo1,2, Chia-Chang Hsu1,3,4, Tsung-Chin Wu1,4, Yu-Chan Li1,4, Chih-Wen Lin1,2,3,4 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, Kaohsiung, Taiwan2 Health Examination Center, E-Da Hospital, Kaohsiung, Taiwan3 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan4 Background: The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear.

Aims: This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.

Methods: We analyzed the treatment and OS of 401 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC between 2012 and 2017.

Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the KaplanMeier method.

Results: The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥ 5 cm, serum AFP ≥ 200, and serum albumin ≥ 3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multipleline treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib

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alone.

Conclusions: Sorafenib with concurrent multipleline therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

P.100

PREDICTIVE FACTORS FOR HEPATOCELLULAR CARCINOMA OCCURRENCE OR RECURRENCE AFTER DIRECT-ACTING ANTIVIRAL AGENTS IN PATIENTS WITH CHRONIC HEPATITIS C Hidehito Honda, Yu Yoshimasu, Yoshihiro Furuichi, Yoshitaka Kasai, Hirohito Takeuchi, Katsutoshi Sugimoto, Takao Itoi Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan Background: Direct-acting antiviral agents (DAAs) and the risk of hepatocellular carcinoma (HCC) is controversially reported in the literature.

Aims: The primary endpoints of this study were to clarify the cumulative incidence and recurrence rate of HCC after DAA treatment. The secondary endpoints were to identify the factors associated with the occurrence or recurrence of HCC after DAAs treatment.

Methods: Of 234 HCV patients, 211 with no history of HCC (no-HCC-history group) and 23 with previous treated HCC history (HCC-history group) were treated with DAAs and followed for more than 24 weeks to determine the incidence of HCC. Platelet count, albumin, Îą-fetoprotein (AFP) level, L3%, the FIB-4 index and APRI scores were analyzed as possible factors associated with HCC occurrence and recurrence.

An intergroup comparison was made of the cumulative incidence of HCC. Results: The median observation period was 21 months. Cumulative incidence of HCC was higher in the HCC-history group than in the noHCC-history group (p < 0.0001, 19.0 and 0.52 per 100 patient-years, respectively). Univariate analysis revealed platelet count, albumin, Îą-fetoprotein (AFP) level, AFP-L3%, and FIB4 index and APRI scores at the end of DAA treatment as being significantly associated with occurrence/recurrence of HCC. Multivariate analysis revealed that AFP levels before and after the administration of DAAs and AFP-L3% after DAA were independently associated with the

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occurrence/recurrence of HCC (p=0.045, 0.043, 0.005, respectively).

Conclusions: The HCC occurrence rate after DAA treatment was very low, and the recurrence rate lower than that in previous interferon reports.

The AFP level and AFP-L3% were identified as important factors in predicting occurrence/ recurrence of HCC. Careful observation is needed when increased levels of AFP or AFP-L3% after DAAs treatment are observed.

P.101

TIP60-DEPENDENT ACETYLATION OF THE SPZ1-TWIST COMPLEX PROMOTES EPITHELIALMESENCHYMAL TRANSITION AND METASTASIS IN LIVER CANCER Shen-Nien Wang Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Background: Metastasis is the main cause of cancer mortality. It is said that the triggering mechanisms and regulation of epithelialmesenchymal transition (EMT) factors are crucial in the commitment of metastasis.

Aims: Increased expression of TWIST1, a basic helix-loop-helix (bHLH) transcription factor, can promote EMT. However, the molecular pathways through which TWIST1 are regulated during metastasis have not been well characterized. The spermatogenic leucine zipper Methods: A variety of in-vitro and in-vivo assay were used. An RTK inhibitor (Sorafenib) and a monoclonal anti-VEGF antibody (Avastin) were also employed to examine the mechanisms by which SPZ1 and TWIST1 exert in HCC. Results: The HIV-1 Tat-interacting protein 60kDa (Tip60) acetyltransferase mediates acetylation at lysine residues of SPZ1 at positions 369 and 374, and of TWIST1 at positions 73 and 76, which are required for SPZ1-TWIST1 complex formation and cancer cell migration in vitro and in vivo. Ectopic SPZ1 and TWIST1 expression, but not that of TWIST1 alone, enhanced vascular endothelial growth factor (VEGF) expression via the recruitment of bromodomain-containing protein 4 (BRD4), thus enhancing RNA-Pol IIdependent transcription and inducing metastasis.

Neutralization of VEGF using humanized monoclonal antibodies such as Avastin, eďŹ&#x20AC;ectively abrogated the EMT and oncogenesis induced by the acetylated SPZ1-TWIST1 complex.

Conclusions: SPZ1 overexpression was shown to promote angiogenesis, EMT, and metastasis by interacting with TWIST1 and activating it. These results highlight its potential as a therapeutic target in angiogenesis and metastasis of HCC.

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Section：GI P.102

A MULTICENTER, RANDOMIZED CONTROLLED TRIAL OF CARVEDILOL IN THE SECONDARY PROPHYLAXIS OF GASTRIC VARICEAL BLEEDING Wen-Chi Chen1,2, I-Fang Hsin2,3, Ping-Hsien Chen2,3, Yen-Po Wang2,3, Jin-Shiung Cheng1,2, Ming-Chih Hou2,3,4,5 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan3 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan4 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan5

Carvedilol 用於預防胃靜脈曲張再出 血：一隨機多中心研究 陳文誌1,2 辛怡芳2,3 陳炳憲2,3 王彥博2,3 鄭錦翔1,2 侯明志2,3,4,5

the group that received repeated GVO and 14 patients (23%) in the group that received repeated GVO plus carvedilol (P=0.18). Ascites (relative risk [RR], 2.69; 95% CI, 1.33–5.48; P=0.006) and hepatoma (RR, 2.10; 95% CI, 1.03–4.28; P=0.04) were associated with recurrent GVB. Twentynine patients (48%) in the group that received repeated GVO and 17 patients (28%) in the group that received repeated GVO plus carvedilol had recurrent UGIB (P=0.03). Carvedilol (RR, 0.44; 95% CI, 0.24–0.80; P=0.007) was associated with reduced risk of UGIB recurrence. Ascites (RR, 3.02; 95% CI, 1.59–5.73; P=0.001) and hepatoma (RR, 2.07; 95% CI, 1.10–3.88; P=0.02) were associated with recurrent UGIB. A higher proportion of patients in the group that received repeated GVO plus carvedilol (53%) had adverse events than the group that received repeated GVO (15%) (P＜0.001). Mean survival times were 21±18 months in the group that received repeated GVO vs 25±20 months in the group that received repeated GVO plus carvedilol (P=0.30).

Conclusions: Carvedilol plus GVO could not decrease recurrent GVB but was associated with decreased recurrent UGIB. The combination therapy group had more adverse events. The survival was similar between both groups.

高雄榮民總醫院內科部胃腸肝膽科1 國立陽明大學醫學院2 臺北榮民總醫院內視鏡診斷暨治療中心3 臺北榮民總醫院內科部4 臺北榮民總醫院內科部胃腸肝膽科5 Background: Recurrent gastric variceal bleeding (GVB) is frequent after hemostasis by gastric variceal obturation (GVO).

Aims: This study evaluated the efficacy of carvedilol plus GVO for the secondary prophylaxis of GVB. Methods: A total of 121 cirrhotic patients with acute GVB were randomized into two groups after hemostasis using GVO. Patients allocated to group A (n=61) underwent repeated GVO. Patients allocated to group B (n=60) received repeated GVO plus carvedilol. Recurrent GVB, upper gastrointestinal bleeding (UGIB), adverse events, and survival were compared between the groups.

Results: GVB recurred in 21 patients (34%) in

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P.103

RISK OF DELAYED BLEEDING BEFORE AND AFTER IMPLEMENTATION OF COLD SNARE POLYPECTOMY IN A SCREENING COLONOSCOPY SETTING Yu-Tse Chiu1, Li-Chun Chang1,2, Weng-Feng Hsu1, Chia-Hong Tu1,2, Chieh-Chang Chen1, Ming-Shiang Wu1, Han-Mo Chiu1,2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Health Management Center, National Taiwan University Hospital, Taipei, Taiwan2

篩檢性大腸鏡導入息肉冷切切除術前 後的延遲性術後出血風險之比較

邱毓澤1 張立群1,2 許文峰1 凃佳宏1,2 陳介章1 吳明賢1 邱瀚模1,2 台大醫院內科部1 台大醫院健康管理中心2

Background: Cold snare polypectomy (CSP) is considered to be effective in reducing the risk of delayed bleeding but randomized trials fail to support this owing to the small sample size.

Aims: The present study aimed to compare t he risk o f d el a y e d b l e e d i n g b e fo r e and after implementation of CSP in a screening colonoscopy setting.

Methods: This study retrospectively analyzed a prospectively maintained screening colonoscopy database in a university hospital in Taiwan. We compared the rate of delayed bleeding before and after implementation within similar periods (18 months and 15 months) and the respective number of polypectomies (1,304 and 1,255) performed to remove small and diminutive polyps.

The main outcome measurement was delayed bleeding within the two periods. Multivariate analysis was performed to adjust for major confounders.

Results: A total of 1,304 and 1,225 subjects received HSP and CSP in two separate periods, respectively. Compared with the HSP, the CSP had a lower rate of delayed bleeding (0.1% vs.

1.1%, P＜0.001), severe bleeding (0% vs. 0.7%, P＜0.01), need for second-look colonoscopy (0%

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vs. 0.8%, P＜0.01), and emergency service visits (0.1% vs. 1.0%, P＜0.01). Total procedure time (12.60±11.45 vs. 16.48±14.27 min/person, P ＜0.01) and duration of hospital stay (1.18±0.50 vs. 1.53±5.78 hour/person, P＜0.03) were also shorter after CSP implementation. Multivariate analysis showed that HSP was an independent risk factor for delayed bleeding after adjusting for age, gender, and number of polyps (adjusted odds ratio 14.4; 95% confidence interval=1.88-110.6).

Conclusions: Implementation of CSP significantly reduces the risk of delayed bleeding associated with removing small and diminutive polyps in screening colonoscopy.

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P.104

PRIMARY, SECONDARY, AND TERTIARY ANTIBIOTIC RESISTANCE RATES OF HELICOBACTER PYLORI: A COMMUNITY-BASED STUDY Yen-Pin Huang1, Kun-Ching Chou1, Tsung-Hsien Chiang2, Yen-Po Yeh3, Jyh-Ming Liou4, Ming-Shiang Wu4, Yi-Chia Lee4, Wei-Wen Su1 Changhua Christian Hospital, Changhua, Taiwan1 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan2 Changhua County Public Health Bureau, Changhua, Taiwan3 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4

幽門螺旋桿菌的初級、次級和三級抗 生素抗藥率之社區研究 黃彥斌1 周昆慶1 江宗賢2 葉彥伯3 劉志銘4 吳明賢4 李宜家4 蘇維文1 彰化基督教醫院1 台大醫院綜合診療部2 彰化縣衛生局3 台大醫院內科部4

Results: Between 2014 to 2018, 855 participants were enrolled (mean age: 58.5 years and male: 43.9%). In the genotype analyses, primary resistance rates to clarithromycin and levofloxacin were 17.3% (95% CI: 14.7-20.2%) and 15.0% (12.5-17.9%), respectively; secondary resistance rates were 57.5% (42.2-71.5%) and 55.6% (39.670.5xx%), respectively; and tertiary resistance rates were 75.3% (64.9-83.4%) and 52.7% (41.563.7%), respectively. In the MIC analyses, primary resistance rates to clarithromycin, metronidazole, amoxicillin, levofloxacin, and tetracycline were 14.9% (12.1-18.3%), 25.7% (22.0-29.7%), 2.0% (1.1-3.7%), 25.4% (21.8-29.4%), and 4.4% (3.06.6%), respectively; secondary resistance rates were 70.8% (50.8-85.1%), 41.7% (24.5-61.2%), 8.3% (2.3-25.9%), 50.0% (31.4-68.6%), and 4.2% (0.7-20.2%), respectively; and tertiary resistance rates were 75.6% (61.3-85.8%), 61.4% (46.674.3%), 11.1% (4.8-23.5%), 62.2% (47.6-74.9%), and 15.6% (7.8-28.8%), respectively.

Conclusions: The present study demonstrates a stepwise relationship in the primary, secondary, and tertiary resistance rates of H. pylori in a Taiwanese community. Efficacy of 1st-line therapy counts for clarithromycin; but 2nd-line and 3rdline therapies would consider alternative regimen because of clarithromycin and levofloxacin resistances.

Background: Helicobacter pylori infection is the major cause of gastric cancer and its eradication is effective for gastric cancer prevention; however, the rates of antibiotic resistance in the community setting, which can be a barrier to implement such a preventive program remain unclear.

Aims: To evaluate the rates of primary, secondary, and tertiary antibiotic resistance of H. pylori in the community setting in Taiwan.

Methods: We invited residents aged 50-69 years to participate in the community-based screening program in Changhua County using the H. pylori stool antigen test. Subjects testing positive would receive H. pylori eradication with clarithromycinbased sequential therapy and levofloxacin-based retreatment. A subset of H. pylori carriers were invited to determine their antibiotic susceptibility using the genotyping (23S ribosomal RNA and gyrase A mutations) and minimum inhibitory concentration (MIC) methods.

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P.105

AMOXICILLIN SUSCEPTIBILITY CAN DETERMINE THE ERADICATION RATE OF BISMUTHCONTAINING RIFABUTINBASED RESCUE REGIMEN IN REFRACTORY H. PYLORI INFECTION Chung-Tai Wu1,2, Hsiu-Chi Cheng1, Wei-Ying Chen1, Er-Hsiang Yang1, Meng-Ying Lin1, Ming-Tsung Hsieh1, Wei-Lun Chang1, Yu-Chin Tsai3, Hsiao-Bai Yang6, Yao-Jong Yang4, Cheng-Chan Lu5, Bor-Shyang Sheu1,2,3 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan2 Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan3 Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan4 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan5 Department of Pathology, Ton-Yen General Hospital, Hsinchu, Taiwan6

Amoxicillin 感受性可以決定鉍劑合併 Rifabutin 救援療法對難治型幽門桿菌 感染的除菌成功率 吳忠泰1,2 鄭修琦1 陳威穎1 楊貳翔1 林孟穎1 謝明宗1 張維倫1 蔡郁清3 楊曉白6 楊燿榮4 呂政展5 許博翔1,2,3 國立成功大學醫學院附設醫院內科部1 國立成功大學醫學院臨床醫學研究所2 衛生福利部台南醫院內科部3 國立成功大學醫學院附設醫院小兒部4 國立成功大學醫學院附設醫院病理部5 東元綜合醫院病理部6

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Background: International consensus recommends Helicobacter pylori culture with susceptibility testing after failure for the secondline treatment. Despite susceptibility-guided therapy and rifabutin-based regimen are both appropriate subsequent treatment, the efficacy is still unclarified. The eradication rate of rifabutinbased regimen in separate therapeutic lines for H. pylori infection ranges from 58.3% to 96.6% in varieties of studies. Adding bismuth subcitrate on rifabutin-based regimen had been reported to yield additional benefit for eradication rate.

Aims: The study aimed to investigate the efficacy of bismuth-containing rifabutin-based rescue regimen for refractory H. pylori infection.

Methods: H. pylori-infected patients with dual clarithromycin and levofloxacin resistance or twice eradication failure were enrolled into the trial.

After culture for H. pylori susceptibility, all patients received 10-days bismuth-containing rifabutinbased regimen (BPAR-10: bismuth subcitrate 600 mg, pantoprazole 40 mg, amoxicillin 1000 mg and rifabutin 150 mg all twice daily), followed by 13C urea breath test to confirm eradication result. Patients been treated previously by susceptibility-guided clinician-judged regimens were retrospectively selected as control cohort. The primary outcome was to compare the eradication rate between these two groups.

Results: There were 23 and 92 patients enrolled in BPAR-10 and susceptibility-guided regimens respectively. The eradication rate revealed no difference between the BPAR-10 regimen and it was in the susceptibility-guided regimen by both intentional-to-treat analysis (52.2% v.s. 58.7%; OR 0.77 [95% CI 0.31-1.92]; p=0.57) and perprotocol analysis (50.0% v.s. 58.7%; OR 0.70 [95% CI 0.28-1.79]; p=0.46). Within BPAR-10 regimen, eradication failure is associated with amoxicillin resistance, more previous treatment failure episodes (median 3.0 v.s. 2.0; p=0.02), and higher resistant antibiotic amounts (median 4.0 v.s.

2.0; p=0.00). With amoxicillin sensitivity, BPAR10 regimen can achieve satisfactory eradication rate (81.8% v.s. 25.0%; OR 13.50 [95% CI 1.47123.74]; p=0.02).

Conclusions: Compared with susceptibility-guided therapy, BPAR-10 demonstrates similar eradication result for refractory H. pylori infection. Amoxicillin sensitivity is a pivot factor to determine the better successful eradication rate of BPAR-10 regimen..

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COMBINED AMINO ACID POLYMORPHISMS OF CAGI AND CAGL SYNERGISTICALLY IMPROVES GASTRIC CANCER PREDICTION Wei-Lun Chang, Yi-Chun Yeh, Hsin Yu Kuo, Ming-Tsung Hsieh, Meng-Ying Lin, Bor-Shyang Sheu

integrin intensity, especially the high corpus region (3.04 vs. 2.67, p=0.041) compared with those without risky polymorphisms.

Conclusions: Infection by H. pylori carrying cagI 17F125N319G and cagL 58Y59E increases gastric cancer risk via induction of gastric integrin expression. Combined amino acid polymorphisms of cagI and cagL synergistically improve gastric cancer prediction (PPV=58.8%).

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

結合 CAGI 和 CAGL 的氨基酸多型性 能提升幽門桿菌患者罹患胃癌的預測 張維倫 葉怡君 郭欣瑜 謝名宗 林孟穎 許博翔 成大醫院內科 Background: H. pylori use type 4 secretion system (T4SS) to translocate cagA oncoprotein into host cells and induce gastric carcinogenesis.

The cagL and cagI are both components of T4SS. We previously found that amino acid polymorphism of cagL increased gastric cancer risk.

Aims: This study investigated whether cagI amino acid polymorphism can also increase gastric cancer risk?

Methods: A total of 113 patients (gastric ca n ce r=2 3 , n o n - c a n c e r c o n tr o l =9 0 ) wit h H. pylori infection were enrolled. The cagI amino acid polymorphism was determined by direct sequencing and further analyzed for its association with gastric cancer, precancerous lesion, serum pepsinogen I and II levels, and gastric integrin intensity. Pepsinogen level was determined by ELISA. Gastric integrin intensity was determined by immunohistochemistry.

Results: Three cagI amino acid polymorphisms 17F, 125N, and 319G were associated with increased gastric cancer risk either alone or in combination (OR=4.75, 95% CI=1.50-15.07, p=0.008). Combined risky polymorphisms of cagI (17F125N319G) and cagL (58Y59E) significantly increased the GC risk (OR=51.43, 95% CI=5.65468.49, p＜0.001). The cagI 125N also increased the risk of gastric atrophy. Patients with cagI and cagL risky polymorphisms had lower serum PI/PII ratio (8.16 vs. 16.26, p=0.008) and higher gastric

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P.107

ENDOSCOPIC SUBMUCOSAL DISSECTION VERSUS ESOPHAGECTOMY FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CANCER: A SYSTEMATIC REVIEW AND METAANALYSIS OF SAFETY AND LONGTERM OUTCOME Jen-Hao Yeh1,2, Ru-Yi Huang3, Ching-Tai Lee1, Chi-Wen Lin1,2, Ming-Hung Hsu1, Tsung-Chin Wu2, Po-Jen Hsiao2, Wen-Lun Wang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-shou University, Da-Chung Branch, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-shou University, Da-Chung Branch, Kaohsiung, Taiwan2 Department of Family Medicine, E-DA Hospital/I-shou University, Kaohsiung, Taiwan3

內視鏡黏膜下剝離術與食道切除術針 對表淺鱗狀細胞癌的長期預後比較： 系統回顧與統合分析 葉人豪1,2 黃如薏3 李青泰1 林志文1,2 徐銘宏1 吳宗勤2 蕭博仁2 王文 1 義大醫院胃腸肝膽科1 義大大昌醫院胃腸肝膽科2 義大醫院家醫科3 Background: Endoscopic submucosal dissection (ESD) has become the treatment of choice for superficial esophageal squamous cell cancer (SESCC) by its minimal invasiveness and high complete resection rate. However, it is not clear whether ESD has similar long-term outcomes compared to esophagectomy.

Aims: This review is aimed to evaluate the longterm outcomes for SESCC treated by ESD and the comparison to esophagectomy.

Methods: The primary outcomes were overall survival, disease specific survival and recurrence free survival at 5-years. Secondary outcomes included adverse events, R0 resection, locoregional recurrence and distal metastasis.

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Hazard ratio (HR) for survival analysis and odds ratio (OR) for concrete variables were used and expressed with 95% confidence interval (CI).

Results: 3796 patients in 21 retrospective studies were included, and 5 studies compared ESD and esophagectomy directly. Overall survival and disease specific survival at 5-year for ESD were 86.9% and 97.7%. In terms of the comparison between ESD and esophagectomy, there was no difference in the 5-year overall survival (HR=0.66, 95% CI 0.39 - 1.11) and recurrence free survival (HR=1.52, 95% CI=0.74 – 3.09) despite more metachronous recurrence for ESD. Tumor depth (mucosa versus submucosa) was not a predictor of survival regarding to the choice of treatment modality. Procedure time, hospital stay, and adverse events (19.8 % vs. 44.0%, OR=0.3, 95% CI=0.23 - 0.39) were also lower with ESD. Conclusions: For SESCC, ESD should be considered as the first line treatment given the excellent efficacy with less morbidity than esophagectomy.

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P.108

REAL-WORLD TREATMENT PERSISTENCE AND CLINICAL OUTCOMES OF VEDOLIZUMAB IN INFLAMMATORY BOWEL DISEASE PATIENTS IN TAIWAN: RESULTS FROM THE TSIBD REGISTRY Wei-Chen Tai1, Chia-Hung Tu2, Jen-Wei Chou3, I-Che Feng4, Chen-Shuan Chung5, Ming-Jium Shieh6, Hsu-Heng Yen7, Wen-Hung Hsu8, Chien-Yu Lu8, Lung-Sheng Lu1, Shu-Lun Tang9, Peng-Wen Pao9, Pei-Wen Lien9, Yizhou Ye9, Paul Dolin10, Shu-Chen Wei2 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan3 Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan5 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan 7. Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan6 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan7 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan8 Medical Affairs, Takeda Pharmaceuticals Taiwan, Ltd.9 Epidemiology, Takeda Pharmaceutical Company Ltd.10

發炎性腸道疾病患者在真實世界之治 療持續性與臨床結果：台灣發炎性腸 道疾病學會登錄系統之真實世界實證

戴維震1 凃佳宏2 周仁偉3 馮意哲4 鍾承軒5 謝銘鈞6 顏旭亨7 許文鴻8 盧建宇8 盧龍生1 唐述綸9 鮑鵬文9 連珮雯9 葉一舟9 Paul Dolin10 魏淑鉁2 高雄長庚紀念醫院胃腸肝膽科1 國立臺灣大學醫學院附設醫院內科部2 中國醫藥大學附設醫院胃腸肝膽科3 台南奇美醫院胃腸肝膽科4 亞東紀念醫院肝膽胃腸科5 國立臺灣大學醫學院附設醫院腫瘤科6 彰化基督教醫院胃腸肝膽科7 高雄醫學大學附設中和紀念醫院胃腸肝膽科8 台灣武田藥品工業股份有限公司醫藥事務部9 Epidemiology, Takeda Pharmaceutical Company Ltd.10 Background: The pivotal phase 3 GEMINI clinical trial program demonstrated the efficacy and safety of vedolizumab (VDZ) in the treatment of moderately to severely active inflammatory bowel disease (IBD). Real-world evidence generated from Western countries has shown consistent effectiveness and tolerability of VDZ in IBD. However, real-world treatment persistence and clinical outcomes of VDZ in Asian IBD patients remains limited.

Aims: The aim of this study was to assess the treatment persistence outcomes among patients treated with VDZ for Crohn’s disease (CD) or ulcerative colitis (UC) in Taiwan.

Methods: This study analyzed data (collected between Jan 2018 – Apr 2019) from the Taiwan Society of IBD (TSIBD) registry, which prospectively collects data on treatments and outcomes and is updated every three months.

Patients who received at least one dose of VDZ and had at least 6 months of follow-up were analyzed. Treatment persistence, effectiveness (clinical response, clinical remission and steroidfree remission), rates of primary non-response (PNR) and secondary loss of response (SLOR), and adverse events (AE) were analyzed in both UC and CD patients.

Results: A total of 30 patients (UC: 8, CD: 22) starting VDZ therapy with a follow-up visit available on the sixth month were included in this analysis. Of them, 23 (76.7%) were male and the average [standard deviation, SD] age at VDZ initiation was 39.4 [14.3] years (45.8 [13.9] and 37.1 [13.8] years for UC and CD, respectively).

The median duration of disease prior to VDZ

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use was 2.6 years in UC and 4.1 years in CD. The proportion of biologic naïve patients were 62.5% (n=5) in UC and 59.1% (n=13) in CD. At 6 months after treatment initiation, 87.5% (7/8) of UC patients and 90.9% (20/22) of CD patients were persistent on VDZ. The reason for VDZ treatment discontinuation by month 6 was PNR for all patients (10%, 3/30), and no patients discontinued due to serious adverse events or SLOR. Among the UC patients at month 6, 87.5% (7/8) had clinical response to VDZ therapy, 25.0% (2/8) achieved clinical remission [40% (2/5) in bionaïve and 0% (0/3) in bio-experienced patients], and 16.7% (1/6) of patients on steroids at baseline achieved steroid-free remission. Among the CD patients at month 6, 63.6% (14/22) had clinical response to VDZ therapy, 68.2% (15/22) achieved clinical remission [84.6% (11/13) in bio-naïve and 44.4% (4/9) in bio-exposure patients], and 36.4% (4/11) of patient on steroid at baseline achieved steroid-free remission. One patient reported a serious infection (gastrointestinal infection and upper and lower respiratory tract infection) in CD; no UC patients experienced an AE. Conclusions: Results demonstrate high rates of treatment persistence and clinical effectiveness at 6 months of VDZ treatment in IBD patients in real-world clinical practice in Taiwan. More clinical remission was found in bio-naïve patients compared with bio- experienced patients. Results in larger cohorts and at longer follow-up periods are warranted.

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SHORT-TERM PROTON PUMP INHIBITOR USE AND HEPATIC ENCEPHALOPATHY RISK IN PATIENTS WITH DECOMPENSATED CIRRHOS IS Kuang-Wei Huang1, Yi-Chun Kuan2, Chia-Hung Kao3 Division of Gastroenterology, Department of Internal Medicine, Taipei Beitou Health Management Hospital, Taipei, Taiwan1 Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan2 Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan3

在代償不全肝硬化的病人使用短期氫 離子幫浦阻斷劑與肝性腦病變的風險 黃洸偉1 官怡君2 高嘉鴻3 台北市北投健康管理醫院胃腸科1 衛生福利部雙和醫院神經內科2 中國醫藥大學核子醫學科3 Background: Recent studies have raised concerns regarding the possible association between proton pump inhibitor (PPI) and hepatic encephalopathy (HE) in patients with cirrhosis.

A window period of approximately 3–6 months is usually adopted in studies that evaluate HE risk in PPI users.

Aims: The HE risk after short-term PPI exposure remains unclear. We explored the effect of shortterm PPI exposure using a case-crossover study design.

Methods: Records of patients with decompensated cirrhosis having HE diagnosis were retrieved from the Registry for Catastrophic Illness Patient Database, a subpart of the Taiwan National Health Insurance Research Database. PPI use rates were compared for case and control with window periods of 7, 14, and 28 days. The adjusted selfmatched odds ratio (OR) and 95% confidence interval (CI) from a conditional logistic regression model were used to determine the association between PPI use and HE risk.

Results: Overall, 13 195 patients were analyzed.

The adjusted OR for HE risk after PPI exposure

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was 3.13 (95% CI=2.33- 4.20) for the 7-day window, 4.77 (95% CI=3.81-5.98) for the 14day window, and 5.60 (95% CI=4.63-6.78) for the 28-day window. All PPI categories, except omeprazole and pantoprazole, were associated with an increased HE risk. Irrespective of other precipitating factors, such as recent gastrointestinal bleeding or infection, PPI significantly increased HE risk.

Conclusions: Short-term PPI use is significantly associated with HE in patients with decompensated cirrhosis. Physicians should use PPI in these patients for appropriate indications and carefully monitor signs of HE even after short-term exposure.

P.110

THE EFFICACY OF SECOND-LINE REGIMENS FOR HELICOBACTER PYLORI ERADICATION TREATMENT: A SYSTEMIC REVIEW AND NETWORK META-ANALYSIS Yen-Lin Chang1, Yu-Chun Tung1,4, Wen-Shyong Liou1, Sz-Iuan Shiu2,3,4 Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taichung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan2 Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan3 Evidence-based Practice and Policymaking Committee, Taichung Veterans General Hospital, Taichung, Taiwan4

第二線幽門螺旋桿菌除菌治療之功效 比較：系統性回顧和網絡統合分析 張雁霖1 董侑淳1,4 劉文雄1 許斯淵2,3,4 臺中榮民總醫院藥劑部1 臺中榮民總醫院內科部肝膽腸胃科2 臺中榮民總醫院重症部3 臺中榮民總醫院實證決策管理委員會4 Background: The prevalence of antibiotic resistance varies greatly among countries and increases gradually in recent years. Declined first-line Helicobacter pylori (H. pylori) eradication rate becomes a significant healthcare burden and challenge for prescribing adequate secondline eradication therapy. Secondary antibiotic resistance to clarithromycin, metronidazole, and levofloxacin were more than 15% after first-line treatment failure. Optimal second-line eradication regimen to achieve best eradication rate remain elusive.

Aims: We conducted a network meta-analysis to compare the relative efficacy of second-line H. pylori eradication among 18 regimens since 2000 to find the favorable regimens in treatmentexperienced patients.

Methods: We reviewed three major bibliographic databases, including PubMed, Embase, and Cochrane Central Register of Controlled Trials, and enrolled relevant randomized trials and

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cohort studies that evaluated second-line H. pylori eradication rate between January 2000 and September 2018. We performed network meta-analysis by WinBUGS and STATA software and assessed the quality of enrolled articles with RoB 2.0 tool for randomized trials and ROBINS-I tool for non-randomized studies of interventions. The odds ratio (OR) was calculated for the comparative treatment effects between second-line therapies when compared to 7-days clarithromycin-based triple therapy as well as in subgroup analysis.

Results: In our study 66 trials with 10582 treatment-experienced participants were recruited in the network meta-analysis. Among all regimens, add-on therapy of probiotics after and/or during second-line antibiotic therapy (OR 4.39, 95% CrI 1.46 - 12.80), quinolone-based sequential therapy for 10-14 days (OR 3.38, 95% CrI 1.29 - 8.65), quinolone-based quadruple therapy for 10-14 days (OR 3.32, 95% CrI 1.28 - 8.47), addon therapy of probiotics before and/or during second-line antibiotic therapy (OR 3.12, 95% CrI 1.01 - 9.32), and add-on therapy of probiotics during second-line antibiotic therapy (OR 3.03, 95% CrI 1.09 - 8.22) had greater efficacy with statistical significance. Besides regimens with longer duration tend to show higher efficacy of eradication compared with regimens with shorter duration.

Conclusions: In our meta-analysis we found add-on therapy of probiotics before/during/after second-line antibiotic therapy, quinolone-based sequential therapy for 10-14 days, and quinolonebased quadruple therapy for 10-14 days are superior to the rest of regimens in treatmentexperienced patients. In addition, extending the duration of regimens achieved higher efficacy of eradication rate than those with shorter duration.

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USE OF PROTON PUMP INHIBITOR AND THE RISK OF DEMENTIA: SYSTEMATIC REVIEW AND METAANALYSIS Tien-En Chang1, Yi-Shin Huang1, Shuo-Ming Ou2, Chin-Lin Perng1, Yi-Hsiang Huang1, Ming-Chih Hou1 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2

質子幫浦阻斷劑與癡呆症之風險：系 統性回顧與統合分析 張天恩1 黃以信1 歐朔銘2 彭清霖1 黃怡翔1 侯明志1 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院內科部腎臟科2 Background: Proton pump inhibitor (PPI) is one of the most common use drugs. Recent studies have shown that PPI may increase the risk of dementia, but it is still inconclusive.

Aims: The aim of this study was to evaluate this association through a systematic review and meta-analysis.

Methods: All qualified literatures with the subject terms “dementia”, “Alzheimer’s disease” and “proton pump inhibitor” in the major medical databases were reviewed.

Results: Eleven studies were eligible for meta-analysis, which has shown PPI was not associated with dementia (risk ratio [RR]=1.04, 95% CI: 0.93 – 1.17, p=0.45), or with Alzheimer’s disease (RR=0.99, 95% CI: 0.81 – 1.21, p=0.90).

Subgroup analysis revealed PPI use was not related to dementia in either prospective studies (RR=1.31, 95% CI: 0.91 – 1.89, p=0.14) or in case-control studies (RR=0.94, 95% CI: 0.85 – 1.05, p=0.27). Furthermore, cumulative dose of PPI was not associated with the risk of dementia in both linear (RR=1.00, 95% CI: 0.99 – 1.00, p=0.42) and curvilinear models.

Conclusions: PPI does not increase the risk of dementia or Alzheimer’s disease. However, further pharmacovigilance to this important issue should be continued.

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P.112

THE PREVALENCE AND RISK FACTORS FOR CANDIDA ESOPHAGITIS IN HIV NEGATIVE GENERAL POPULATION IN TAIWAN Chia-Ming Lu1, Ping-I Hsu1,3, Kung-Hung Lin1,2,4, Hsien-Chung Yu1,2, Wen-Chi Chen1,3, Yan-Hua Chen1,2,4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 Health Evaluation Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan2 National Yang Ming University, Taipei, Taiwan3 Department of Nursing, Meiho University, Pingtung, Taiwan4

念珠菌食道炎在台灣一般族群的流行 病學及危險因子 呂家名1 許秉毅1,3 林恭弘1,2,4 余憲忠1,2 陳文誌1,3 陳彥樺1,2,4 高雄榮民總醫院內科部胃腸肝膽科1 高雄榮民總醫院健康管理中心2 國立陽明大學3 美和科技大學4 Background: Candida esophagitis is a fungal infection of the esophagus caused by Candida species. It is one of the most common esophageal infection and opportunistic gastrointestinal disorder among human immunodeficiency virus (HIV)-positive population. The epidemiology and endoscopic finding of Candida esophagitis among healthy individuals in Taiwan is rarely reported before.

Aims: The aims of this study were (1) to evaluate the prevalence of Candida esophagitis, and (2) to determine the risk factors for Candida esophagitis in health check-up population in Taiwan.

Methods: Between 2015 January and 2018 December, all consecutive outpatients who underwent routine esophagogastroduodenoscopy (EGD) examination as part of a health checkup at their own expense at the Health Evaluation Center of the Kaohsiung Veterans General Hospital, Taiwan, were included in this study.

Clinical data including personal information, medical history, symptoms from questionnaire,

laboratory data, body weight, body mass index (BMI), body fat percentage, endoscopic report, and pathology report were collected by retrospective chart review method. Candida esophagitis was suspected when white plaques coating over esophageal mucosa was identified endoscopically and cannot be washed away. The diagnosis was confirmed by endoscopic biopsy for pathological assessment with hematoxylin and eosin and Periodic Acid-Schiff staining.

Subjects with history of HIV infection, with positive HIV antibody blood tests, or refusing biopsy examination were excluded.

Results: A total of 11802 outpatients receiving EGD examination were included in this study.

Candida esophagitis was diagnosed and confirmed by histology examination in 47 individuals, with an overall prevalence of 0.4%.

The mean age was significantly higher in individuals with Candida esophagitis than in those without Candida esophagitis. Alcohol consumption and chronic kidney disease (CKD) were more common among Candida esophagitis subjects.

Multivariate analysis revealed that older age (odds ratio [OR], 1.029; 95% confidence interval [CI], 1.003–1.056; P=0.029), alcohol consumption (OR, 2.103; 95% CI, 1.150–3.846; P=0.016), and CKD (OR, 12.605; 95% CI, 4.289–37.043; P＜ 0.001) were significant risk factors for Candida esophagitis.

Conclusions: Current prevalence of Candida esophagitis is 0.4% in Taiwan HIV-negative general population. Old age, alcohol consumption, and CKD were significant risk factors for Candida esophagitis.

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ASSOCIATION BETWEEN ANTIBIOTIC RESISTANCE AND ERADICATION RATE OF HELICOBACTER PYLORI IN CHILDREN IN TAIWAN Da-Jyun Su1,2, Mei-Hwei Chang1, Yen-Hsuan Ni1, Huey-Ling Chen1, Hong-Yuan Hsu1, Jia-Feng Wu1 Department of Pediatrics, National Taiwan University Children Hospital, Taipei, Taiwan1 Department of Pediatrics, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan2

台灣孩童幽門桿菌抗藥性及其除菌成 功率之相關性研究 蘇大鈞1,2 張美惠1 倪衍玄1 陳慧玲1 許宏遠1 吳嘉峯1 台大醫院小兒部1 輔仁大學附設醫院兒童醫學部2 Background: Eradication of Helicobacter pylori is becoming an important issue of children. It was associated with antimicrobial susceptibility of the region according to previous studies.

Aims: Our study aim to investigate the antibiotic resistance of Helicobacter pylori among children in Taiwan and the association between antibiotic resistance and eradication rate of different therapeutic regimens.

Methods: We enrolled 61 treatment-naïve children with positive Helicobacter pylori culture result from January 2009 to November 2018 retrospectively. The differences of antibiotic resistance between 2009-2013 and 20142018 were compared. Only 46 patients were treated with either triple therapy for either 7 days or 14 days, or 14 days of sequential therapy, and completed the required exam to evaluate the eradication success. Eradication success was defined as negative 13C-Urea breath test, histology or culture result performed at least 4 weeks after the end of treatment.

Results: 61 children (40 males, mean age 13.2 years) whose culture of Helicobacter pylori was positive were enrolled in this study. The overall antibiotic resistance of clarithromycin, metronidazole, levofloxacin and amoxicillin were 23%, 23%, 6.5% and 2.1% respectively.

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Clarithromycin resistance decreased from 25% in 2009-2013 to 20% in 2014-2018, and metronidazole resistance increased from 19.4% to 28% between these two periods. In the subgroup of patient who received treatment and completed the evaluation of eradication, we found clarithromycin resistance was associated with the failure of 7-day and 14-day triple therapy (p=0.001 and 0.038, respectively) but not 14-day sequential therapy (p=0.16). Besides, metronidazole and levofloxacin resistance were not associated with failure of any therapeutic regimens.

Conclusions: In our study, clarithromycin resistance was associated with eradication failure of triple therapy but not sequential therapy in Taiwanese children.

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THE EFFICACY OF DEXLANSOPRAZOLE MR-BASED NON-BISMUTH QUADRUPLE (CONCOMITANT) THERAPY FOR FIRST LINE HELICOBACTER PYLORI ERADICATION: A PROSPECTIVE RANDOMIZED TRIAL Tzu-Hsin Huang1, Wei-Chen Tai1,2, Chih-Ming Liang1, Keng-Liang Wu1,2, Pin-I Hsu3, Deng-Chyang Wu4, Seng-Kee Chuah1,2 Division of Hepatogastroenterology; Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Chang Gung University College of Medicine, Kaohsiung, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan3 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan4

雙重劑型釋放 Dexlansoprazole MR 使用於「不含鉍劑四合療法」在第一 線幽門螺旋桿菌除菌治療之療效：前 瞻性隨機試驗 黃子昕1 戴維震1,2 梁志明1 吳耿良1,2 許秉毅3 吳登強4 蔡成枝1,2

dependent dissolution profiles.

Aims: We performed a prospective, randomized controlled study to assess the efficacy of Dexlansoprazole MR-based Concomitant therapy and investigate the influencing clinical factors.

Methods: We recruited 202 out of 248 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 7-day Dexlansoprazole MRbased Concomitant therapy (Dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily. and metronidazole 500 mg twice daily for 7 days, DACM group) or a 7-day lansoprazole-based Concomitant (Lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days, LACM group). Urea breath tests were followed-up 8 weeks later.

Results: The eradication rates for DACM and LACM groups were 86.1% (95% CI=77.8%92.2%) and 90.1% (95% CI=82.6%-95.2%) (p=0.384) in ITT analysis; 90.6% (95% CI=82.9%95.6%) and 92.6% (95% CI=85.5%-96.9%) (p=0.572) in PP analysis. The adverse event rates were 11.5% versus 10.2% in the 2 groups (p=0.779). The H. pylori culture positive rate was 90.5%. The antibiotic resistance rates were amoxicillin (0%), clarithromycin (21%) and metronidazole (26.32%).

Conclusions: Dexlansoprazole MR-based Concomitant therapy achieves a high PP eradication rate for the first-line anti-H. Pylori therapy comparable to 7-day Lansoprazole-based Concomitant therapy.

長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系1 長庚大學醫學院2 高雄榮民總醫院內科部胃腸肝膽科3 高雄醫學大學附設中和紀念醫院內科部胃腸內科4 Background: Non-Bismuth containing quadruple therapy (Concomitant therapy) can achieve a promising success rate of＞90-% in the presence of clarithromycin resistance. High dose PPI is needed with a dosage of twice daily but when a dual delayed release formulation PPI in capsules for oral administration (Dexlansoprazole MR), a once daily dose may be need only. The capsules contain dexlansoprazole in a mixture of two types of enteric-coated granules with different pH-

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SURVEY THE UPDATED PREVALENCE OF H. PYLORI INFECTION IN TAIWAN Mei-Jyh Chen 1, Yu-Jen Fang2, Ming-Shiang Wu1, Chieh-Chang Chen1, Wen-Hao Hu3, Jyh-Ming Liou1 National Taiwan University Hospital, Taipei, Taiwan1 National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan2 National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan3

台灣地區幽門螺旋桿菌盛行率之更新 調查 陳美志1 方佑仁2 吳明賢1 陳介章1 胡文皓3 劉志銘1 台大醫院1 台大醫院雲林分院2 台大醫院新竹分院3 Background: The reported prevalence of Helicobacter pylori (H. pylori) infection in Taiwan was 54.4% in 1992. An updated prevalence of H. pylori infection in asymptomatic adults is lacking in Taiwan.

Aims: We aimed to assess the updated agestandardized prevalence of H. pylori infection in asymptomatic subjects and in patients with dyspepsia and to assess the accuracy of H. pylori stool antigen (HpSA) test for screening of H. pylori in Chinese population.

Methods: Asymptomatic adult subjects (N=189) were screened for H. pylori infection using HpSA, serology, and 13C-Urea Breath Test (13C-UBT) in 2016-2017. Adult patients with dyspepsia (N=145) were screened for H. pylori using 13C-UBT, HpSA, serology, rapid urease test, and histology during 2016-2018. Two types of HpSA, including the Diagnostec® HpSA ELISA Kit (HpSA ELISA) and Rapid Test Kit (HpSA Rapid) were used in this study. Sensitivity, specificity and accuracy of the HpSA tests were calculated using the 13C-UBT as golden standard test.

Results: The un-adjusted prevalence of H. pylori was 21.2% in asymptomatic adults and 37.9% in patients with dyspepsia (p＜0.001). The agestandardized prevalence of H. pylori was 28.9% in asymptomatic adults in Taiwan. Of the 334 patients included for analysis, the area under

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the curve of HpSA ELISA test was 0.978, and the optimal cut-off value of OD was 0.03. The sensitivity, specificity, and accuracy of the HpSA ELISA were 0.929, 0.983, and 0.967, respectively.

The sensitivity, specificity, and accuracy of the HpSA Rapid were 0.929, 0.958, and 0.949, respectively.

Conclusions: The prevalence of H. pylori infection has decreased in Taiwan. HpSA test is an accurate tool for screening of H. pylori for Chinese population.

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THE ROLE OF INSULIN-LIKE GROWTH FACTOR AXIS IN THE PROGRESSION AND SURVIVAL IN GASTRIC CANCER Tzu-Chan Hong1, Jyh-Ming Liou1, Kun-Feng Tsai2, Jaw-Town Lin3, Ming-Shiang Wu1 Department of Internal Medicine, National Taiwan University Hospital, Taiwan1 Department of Internal Medicine, Gastroenterology and Hepatology Section, An Nan Hospital, China Medical University, Tainan, Taiwan2 Center for Digestive Medicine, China Medical University Hospital, Taiwan3

類胰島素生長因子軸在胃癌的預後和 存活角色分析 洪子瞻1 劉志銘1 蔡坤峰2 林肇堂3 吳明賢1 台大醫院內科部1 臺南市立安南醫院消化內科2 中國醫藥大學附設醫院消化醫學中心3 Background: Insulin-like growth factors (IGFs) play an important role in tumor growth, survival and metastatic activities. Their effects are regulated by the homeostasis of IGFs and their binding proteins (IGFBPs). The overexpression of IGFs and IGFBPs has been reported to be associated with the progression and survival of several cancers. However, their roles in the progression of gastric cancer remain poorly understood.

Aims: We aimed to assess the impact of circulating levels of IGFs (IGF1, IGF2) and IGFBPs (IGFBP1, IGFBP2, IGFBP3) and the expression of IGFBP2 in gastric cancer tissues on the progression and survival of gastric cancer.

Methods: A total of 481 gastric cancer patients were enrolled in this prospective hospital-based cohort study. Another 114 subjects without gastric cancer were recruited as control group.

Plasma levels of IGF1, IGF2, IGFBP1, IGFBP2, and IGFBP3 were determined by commercially available enzyme-linked immunosorbent assay or radioimmunoassay kits. Expression of IGFBP2 was assessed by immunohistochemical stains.

Their impacts on gastric cancer survival were analyzed by log-rank test and Cox proportional

hazards regression models.

Results: Plasma levels of IGFBP2 was significantly higher in patients with gastric cancer as compared to healthy controls (p＜0.001).

Plasma levels of IGFBP2 was also significantly higher in patients with more advanced AJCC stages (p＜0.001). However, the plasma levels of IGF1, IGF2, IGFBP1, and IGFBP3 were not significantly differed in gastric cancer patients and controls. Patients with the highest tertile of IGFBP-2 levels were associated with a worse overall survival compared to those with the lowest IGFBP2 tertile levels (Hazard Ratio=1.51, 95% CI=1.19-1.92, p=0.001) after adjustment for age, gender, location, histology type, depth of invasion, and nodal metastasis. Higher expression of IGFBP2 in gastric cancer tissues was also associated with a worse overall survival than those with lower expression of IGFBP2, after adjustment of the above variables. In contrast, the plasma levels of IGF1, IGF2, IGFBP1, and IGFBP3 were not correlated with the overall survival in gastric cancer patients.

Conclusions: IGFBP2 plasma level, but not IGF1, IGF2, IGFBP1, or IGFBP3 levels, was higher in patients with gastric cancer and correlated with stage and survival. Higher expression of IGFBP2 in gastric cancer tissues also correlated with a worse overall survival. The finding lends support that IGFBP2 is a potential therapeutic target for gastric cancer.

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Jyong-Hong Lee, Chi-Chieh Yang, Kwei Ming Chen

Jeng-Shiann Shin, Jen-Chieh Huang, Cheng-Chi Lee , Chi-Hung Chen, Yi-Chih Wen, Hung-Yao Chen-Cheng

ENDOSCOPIC SUBMUOSAL DISSECTION FOR SUPERFICIAL PHARYNGEAL SQUAMOUS CELL CARCINOMA Division of gastroenterology, Department of internal medicine, Show Chwan Memorial Hospital, Changhua, Taiwan

內視鏡黏膜下剝離術治療表淺咽喉麟 狀上皮細胞癌 李炯宏 楊基滐 陳奎閔 秀傳醫療社團法人秀傳紀念醫院肝膽胃腸內科 Background: The early detection rates of superficial pharyngeal squamous cell carcinoma (SPSCC) by using narrow-band imaging is increasing. Importantly, endoscopic submucosal dissection (ESD) provides promising outcomes by experienced endoscopists.

Aims: The aims of this study were to clarify the feasibility of ESD for SPSCC and its safety and outcomes.

Methods: In total, 10 patients with 11 lesions were treated by ESD between January 2015 and June 2019. We assessed tumor size, macroscopic type, endoscopic methods, procedure time, histopathologic results, resection results, local recurrence, and adverse events.

Results: En bloc resection rate and complete resection rate are 91% (10/11) and 36% (4/11) respectively. Two patients encountered laryngeal edema and one had subcutaneous emphysema.

All the three patients recovered after conservative treatment and discharged uneventfully. There was one patient with local recurrence but all ten of our patients survives (100%) during follow-up.

Conclusions: ESD for superficial pharyngeal cancer is a safe and feasible treatment with excellent outcome.

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CLINICAL EXPERIENCE OF COLD SNARE POLYPECTOMY IN MANAGEMENT OF SPORADIC GASTRIC POLYPOSIS

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cheng Ching General Hospital, Taichung, Taiwan

冷勒除器切除多發性胃息肉症息肉的 臨床使用經驗 辛政憲 黃仁杰 李政祺 陳季宏 溫弈志 陳鄭弘堯 澄清綜合醫院胃腸肝膽科 Background: Gastric polyps are usually found incidentally during esophago-gastroduodenoscopy (EGD) for related or unrelated indication. Approximately 6% or lower rate of EGD procedure was reported in different countries. Sporadic gastric polyposis shares high percentage in those polyp subgroup. Although only in rare cases cause symptoms, the diagnosis and appropriate management are important as its malignant potential and bleeding risk. In recent years, cold snare polypectomy CSP) technique is more extensively applied to remove the diminutive or small colon polyp with ease and safety.

Aims: Clinical characters of sporadic gastric polyposis The safety and completeness of CSP in managing sporadic gastric polyposis.

Methods: During June 01, 2016 to December 31, 2018, all the EGD endoscopy was reviewed to identify the cases of sporadic gastric polyposis received CSP from the executive health management center of Cheng Ching General Hospital. Age, gender, co-morbidity, polyp characters (size, number, Paris classification and location), CSP procedure (number of polypectomy in each session, complication and pathology), Helicobacter pylori (H.P) infection and colonoscopy result are all the variables. The CSP technique is the same as in removing colon polyp in the literature except traditional endoscopic snare (Olympus, Co.Ltd) being applied. After CSP, PPi, H2- blocker or sucralfate suspicion were prescribed for 3-7 days. Complication including bleeding, pain or perforation is followed up by

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phone within 3 days in outpatient case.

Results: Total fourteen sporadic gastric polyposis who had received CSP were identified with age (33-64 years old, mean 49.9), gender (male:female=3:11), co-morbidity (1/14, cervical cancer), the mximal polyp size in each case (4-20 mm, mean 7.1 mm), polyp number by decade units (1-4 decades, mean 3.1 decades), Paris classification (0-Isp: 0-Is+ -Isp 1:13), polyp location (body: antrum: fundus+body: body+antrum=7:4:3), total number of polyps of each CSP session (3-35, mean=13.6), complication (0), pathology (fundic, hyperplastic, fundic + hyperplastic=11:1:2), H.P infection (0) and colonoscopy (4/12 with hyperplastic or tubular polyp).

Conclusions: (1) Sporadic gastric polyposis is female predominant and polyps majorly distribute at the body and antrum. (2) With the predominant Paris classification 0-Is or -Isp morphology of polyp, CSP is a favourable technique to perform polypectomy without bleeding or perforation. (3) CSP by traditional polypectomy snare is a safe and quick technique to remove polyp without number limitation in each session. (4) Most sporadic gastric polyposis is belong to fundic gland type. But, mixed hyerplastic and fundic polyposis (15%) is firstly reported in this study. (5) Eradication of polyp in sporadic gastric polyposis

by CSP should be performed in the future for clinical and pathological reason. (6) Sporadic gastric polyposis is negative prediction of H.P infection.

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INCREASING ANTIMICROBIAL RESISTANCES IN PEDIATRIC HELICOBACTER PYLORI INFECTION IN SOUTHERN TAIWAN: A COMPARISON BETWEEN TWO DECADES Chi-Wen Hung1,4, Fu-Ping Lai1, Hsiao-Yu Lo1,3, Yao-Jong Yang1,3, Bor-Shyang Sheu2,3 Departments of Pediatrics, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan1 Departments of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan2 Departments of Institutes of Clinical Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan3 Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan4

台灣南部地區兒童胃幽門螺旋桿菌抗 藥性攀升：過去二十年之比較 洪綺彣1,4 賴馥蘋1 羅筱淯1,3 楊燿榮1,3 許博翔2,3 成功大學醫學院附設醫院小兒部1 成功大學醫學院附設醫院內科部2 成功大學醫學院附設醫院臨床醫學研究所3 高雄榮民總醫院兒醫部4 Background: Antimicrobial resistance of H. pylori reduces the eradication rate.

Aims: This study aimed to investigate changes in antimicrobial susceptibility of H. pylori isolated from children in Taiwan in the past two decades.

Methods: We enrolled children receiving esophagogastroduodenoscopy for upper gastrointestinal diseases in a tertiary referral centre from 1998 to 2018. H. pylori infection was diagnosed by culture. The minimal inhibitory concentrations (MICs) of antibiotics were tested using the E-test. The rates of antimicrobial resistance and MICs of amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were compared between 1998-2008 and 2009-2018.

Results: A total of 70 Helicobacter pylori isolates (29 from 1998-2008 and 41 from 2009-2018) were

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identified. The esophagogastroduodenoscopy findings included duodenal ulcers (n=31), gastric ulcers (n=9), and gastritis (n=30).

The overall antimicrobial resistance rates of amoxicillin, clarithromycin, metronidazole, and levofloxacin were 2.9%, 22.9%, 21.4%, and 8.3%, respectively. The dual resistance rate to clarithromycin and metronidazole was 10%. None of the isolates were resistant to tetracycline.

Compared with the isolates from 1998-2008, those from 2009-2018 had higher resistance rates to clarithromycin (26.8% vs. 17.2%, P=0.35) and metronidazole (26.8% vs. 13.8%, P=0.19), but not levofloxacin (9.8% vs. 5.3%, P=1.0). However, emerging resistance to metronidazole/levofloxacin (4.9%) occurred in 2009-2018.

Conclusions: The antimicrobial resistance rates of pediatric H. pylori isolates to clarithromycin and metronidazole increased during the past decade.

The selection of antimicrobial agents other than clarithromycin and metronidazole is crucial to increase pediatric H. pylori eradication rates.

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RISK FACTORS AND CLINICAL OUTCOMES OF ESOPHAGEAL CANDIDIASIS – A SINGLE HOSPITAL EXPERIENCE Yu-Xiang Shen, Chia-Long Lee, Chih-Sheng Hung, Tien-Chien Tu, Chi-Kun Chiang, Ting-Chun Huang, Hsin-Yu Chen Cathay General Hospital, Taipei, Taiwan

食道念珠菌感染之相關危險因子及預 後 沈煜翔 李嘉龍 洪志聖 涂天健 江技坤 黃鼎鈞 陳信佑 國泰醫療財團法人國泰綜合醫院 Background: Esophageal candidiasis is a common fungal infection in immunocompromised patients. However, some patients, who had no systemic immune deficiency, may have esophageal candidiasis due to systemic or topical steroid use, antibiotics, DM or esophageal dysmotility and so on.

Aims: We studied the immunocompetent patients, who had esophageal candidiasis proven by pathological report in the past 10 years in Cathay general hospital, for the demographics, risk factors and clinical outcomes after anti-fungal treatments were prescribed or not.

Methods: Inclusion: patients who are suspected with esophageal candidiasis by endoscopy, proven by biopsy. Exclusion: no detailed medical record. Group stratification: Asymptomatic (group 1), symptomatic (group 2). Statistical analysis: Chi-square Test.

Results: Ninety-nine patients were included in this study for demographic, risk factors and clinical outcomes. 88 of the 99 patients are asymptomatic (group 1) as esophageal candidiasis was diagnosed. 52 patients were treated with antifungal medication (51 patients were still asymptomatic after treatments). 36 patients were not treated with anti-fungal medication (36 patients were asymptomatic at last follow-up).

There were only 11 patients in group 2. Anti-fungal treatments were prescribed with Fluconazole or Nystatin for 7 to 14 days if the patients were treated. The patients in the group 1 without antifungal treatments were all asymptomatic at

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last follow-up. After analysis of risk factors, the proportions of esophageal dysmotility and cancer history were higher in group 2 (esophageal dysmotility: 5.7% (asymptomatic) vs. 27.2% (symptomatic), p=0.038; cancer history: 14.8% (asymptomatic) vs. 45.5% (symptomatic), p=0.022). The underlying causes of group 1 and group 2 had no significant difference (p=0.074).

The endoscopic findings of group 1 and group 2 also had no difference (p=0.059) but a trend of higher proportion of erosions/ulcers in group 2.

Conclusions: The proportions of esophageal dysmotility and cancer history were higher in symptomatic candidiasis. Asymptomatic esophageal candidiasis may not be treated with anti-fungal medication.

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ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCERS Le Quang Nhan3, Tran Ly Thao Vy3, Ho Le Minh Quoc5, Vo Pham Phuong Uyen2, Dang Minh Luan2, Mai Vien Phuong3, Ngo Hoang Minh Thien5, Tran Thai Ngoc Huy 4, Vu Quang Hung1, Le Dinh Quang2, Pham Minh Hai4, Hoang Danh Tan1,5, Le Quang Nghia1 General Surgery Department, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam1 Internal Medicine Department, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam2 Endoscopy Department, University Medical Center at Ho Chi Minh City, Vietnam3 Deparment of Hepatobiliary and pancreatic Surgery, University Medical Center at Ho Chi Minh City, Vietnam4 Digestive Surgery Department, University Medical Center at Ho Chi Minh City, Vietnam5 Background: Gastric cancer is the third leading cause of cancer death. In the last decade, early gastric cancer (EGC) has been reported by using narrow-band imaging (NBI) magnifying endoscopy and endoscopic submucosal dissection (ESD) was performed for these early gastric cancers.

Aims: To assess the initial results of ESD for EGC in Vietnamese patients.

Methods: This is a case series study of 50 Vietnamese patients. These patients were treated

by ESD from Jan 2015 to Dec 2018 in the GI endoscopy department of University Medical Center, Ho Chi Minh city.

Results: There were 50 cases of EGC. Of them, there were 1 case of low grade dysplasia, 47 cases of high grade dysplasia and 2 cases of welldifferentiated adenocarcinoma in the stomach.

There were 41/50 (82%) cases of intramucosal cancers (Tis) and the type 0-IIa+IIc lesions (Japanese classification of early gastrointestinal cancers) was predominant type (58%). There were no complications such as perforation or bleeding. 10 first cases have been following up 36 months and 19 other cases have been following up 24 months without any recurrence.

Conclusions: Our study shows that ESD was the effective and safe for early gastric cancers in Vietnamese patients.

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ENDOSCOPIC SUBMUCOSAL DISSECTION APPLICATION ON SUBEPITHELIAL TUMOR: EXPERIENCE IN A SINGLE MEDICAL CENTER Wang-De Hsiao, An-Ti Chang, Chi-Ting Yang, Chun-Fu Ting, Wen-Hsin Huang Department of Gastroenterology and Hepatology, China Medical University Hospital, Taichung, Taiwan

內視鏡黏膜下剝離術（ESD）應用在 上皮下腫瘤：在單一醫學中心的經驗 蕭望德 張安迪 楊其穎 丁俊夫 黃文信 中國醫藥大學附設醫院內科部消化系 Background: Endoscopic submucosal dissection (ESD) is a minimal invasive endoscopic procedure to deal with early gastrointestinal tumor. Initial, it was developed to resect mucosal neoplasm since 2000 and extended the application to subepithelial tumor in following years. Althrough the similar skills of ESD for subepithelial tumor compared to mucosal lesion. There was some opposition or question of the indication of ESD to subepithelial tumor.

Aims: The objective of the study was to evaluate the safety and efficacy of the procedure of ESD in subepithelial tumor.

Methods: In this retrospective study, we reviewed all patients who underwent endoscopic submucosal dissection for subepithelial tumor in China Medical University Hospital from January 2017 to May 2019.

Results: A total 131 neoplastic lesion in 128 patients of mean age 54.9±33.1years (range, 22-88 years) were enrolled. A total of 16 esophageal lesion (including 10 leiomyoma, 3 cystic lesion, 1 gastrointestinal stromal tumor, 1 Melanoma, 1 Granular cell tumor), 110 gastric lesion (56 gastrointestinal stromal tumor, 36 leiomyoma, 6 heterotopic pancreas, 7 lipoma, 2 schwannoma, 1 neuroendocrine tumor, 1 paraganglioma, 1 angiolipoma), 2 duodenal lesion (all showed neuroendocrine tumor), 3 Rectal lesion (all showed neuroendocrine tumor) were resected with ESD. The mean size of tumors was 18.1±17.6 mm (range, 5-80 mm).The mean operation time was 41±32 minutes (range, 9-200

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minutes).There was one ESD-related signification complication as delayed bleeding requiring endoscopy for hemostasis (gastric lesion). Two cases were unsuccessful to resect the tumor under ESD. One, located in less curvature of stomach, was failed because there was severe hiatal hernia with hardly approach even long loop of endoscopy, and then shift to surgical intervention. One, located in cardia, was deeply invasive to muscle that full wall resection was necessary for en bloc resection but we expected the wound post ESD would hardly close. There was no procedure-related mortality.

Conclusions: The ESD is a safe and effect procedure for subepithelial tumor. The procedure time and perforation are related to tumor location, tumor size, the cross section of muscle and if deep invasion of tumor. Before the procedure, the most crucial topics are to predict if full wall resection and possibility of closing wound.

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EFFICACIES OF TAILORED THERAPY VERSUS GUIDELINERECOMMENDED EMPIRICAL THERAPIES FOR ERADICATION OF HELICOBACTER PYLORI – A TREND SURVEY OVER 20 YEARS IN TAIWAN (1999-2018) Chien-Chih Tung1,2, Chi-Tan Hu3, I-Nan Kuo4, Bor-Ru Lin1,2, Hong-Long Wang5, Jin-De Chen6, Mu-Liang Cheng7, Chia-Tung Shun8, Ming-Jium Shieh2, John Y. Kao9, Jyh-Chin Yang2 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hosipital, Taipei, Taiwan1 Department of Internal Medicine, National Taiwan University Hosipital, Taipei, Taiwan2 Department of Medicine, Buddhist Tzu Chi General Hospital and University, Hualien, Taiwan3 Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan4 Department of Statistics, National Taipei University, New Taipei City, Taiwan5 Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan6 Department of Medicine, Mennonite Christian Hospital, Hualien, Taiwan7 Department of Forensic Medicine and Pathology, National Taiwan University Hosipital, Taipei, Taiwan8 Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, United States9

一份從西元 1998 到 2018 在台灣 20 年的趨勢研究：比較根除幽門桿菌治 療使用精準療法和指引推薦的經驗療 法之效力 董建志1,2 胡志棠3 郭怡男4 林伯儒1,2 王鴻龍5 陳錦得6 鄭穆良7 孫家棟8 謝銘鈞2 高永忠9 楊智欽2 台大醫院綜合診療部1 台大醫院內科部2 花蓮慈濟醫院醫學部3 台大醫院新竹分院內科部4

國立臺北大學統計學系5 台大醫院北護分院內科部6 花蓮基督教門諾醫院醫學部7 台大醫院病理部8 美國密西根大學9 Background: The empiric therapies for H. pylori infection in clinical guidelines have been widely used for the past 20 years. However, the cure rate of this infection is decreasing likely attributed to the increase of antibiotic resistance. The importance of antimicrobial susceptibility test (AST) has been documented in many consensus reports. However, the effect of tailored therapy remains controversial because the AST is rarely offered in most areas.

Aims: To compare the evolution of treatment efficacy among tailored therapy and some recommended empiric therapies through a trend survey from 1999 to 2018.

Methods: This retrospective trend survey was performed at 2 medical centers and 3 community hospitals in Taiwan. A total of 16,370 treatment naïve or failure patients who were treated for H. pylori infection and underwent eradication testing were recruited. Successful H. pylori eradication was defined as a negative 13C-UBT result. The regimens for empiric first-line treatment include tailored therapy, clarithromycin-containing triple therapy (CLA-TT), sequential therapy (ST), bismuth-containing quadruple therapy (BQT), and high-dose dual therapy (HDDT). The regimens for empiric rescue treatment include tailored therapy, levofloxacin-containing triple therapy (LEV-TT), BQT, and HDDT. We divided the 20 years of follow-up time into 4-year periods in order to evaluate the trend of treatment efficacies over time. The E-test was performed to evaluate H. pylori resistance to 5 key antibiotics. For the tailored therapy, CLA-TT, LEV-TT, BQT, or HDDT was chosen by the resistance pattern of each patient based on the MIC values of these antibiotics.

Results: The efficacies of tailored therapy and recommended empiric therapies are listed in Table 1. Tailored therapy, HDDT, and BQT maintain a stable and high efficacy in both firstline and rescue treatment during the study period.

However, the efficacies of CLA-TT, ST, and LEVTT are decreasing year by year. The eradication rate of tailored therapy is significantly higher than that of CLA-TT, ST, LEV-TT, and BQT (p＜0.001,

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0.01, or 0.05) in recent 4-year period. However, there is no significant difference between the efficacy of tailor therapy and HDDT. The prevalence of H. pylori resistance to CLA and LEV was found to be increasing. (Table 2) In contrast, there is no significant change to AMO and TET and both remain low. We found the efficacy of CLA-TT, ST, and LEV-TT is impacted by higher prevalence of antibiotic resistance.

Conclusions: Over the past 20 years, we found that the efficacy of tailored therapy remains relatively stable and is higher than empiric CLATT, ST, LEV-TT, and BQT regimens, all of which showed a trend of lower therapeutic efficacies over time except BQT. Of the recommended empiric therapies, HDDT and BQT have stable therapeutic efficacies and are good choice of empiric treatment at present.

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IMPACTS OF H. PYLORI ERADICATION WITH REVERSE HYBRID THERAPY AND BISMUTH QUADRUPLE THERAPY ON THE THE GUT MICROBIOTA Feng-Woei Tsay1,2,6, Kuo-Wang Tsai3,6, Chao-Yu Pan4,6, Jin-Shiung Cheng1, Deng-Chyang Wu5,6, Ping-I Hsu1,2,6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National YangMing University, Kaohsiung, Taiwan1 Diagnostic and Therapeutic Endoscopic Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan2 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan3 Institute of Biomedical Informatics, National Yang-Ming University and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan4 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan5 Taiwan Acid-related Disease and Microbiota (TARD-M) Consortium6

探討「反轉式混合療法」與「含鉍劑 4 合療法」二種胃幽門螺旋桿菌除菌治 療對腸內菌的影響 蔡峯偉1,2,6 蔡國旺3,6 潘昭宇4,6 鄭錦翔1 吳登強5,6 許秉毅1,2,6 高雄榮民總醫院胃腸肝膽科暨國立陽明大學醫學 系1 高雄榮民總醫院內視鏡診斷治療中心2 高雄榮民總醫院教學研究部3 國立陽明大學生物醫學資訊研究所暨中央研究院 生物醫學科學研究所4 高雄醫學大學附設醫院胃腸科暨高雄醫學大學5 台灣胃酸相關疾病暨微菌叢研究群6 Background: Anti-H. pylori therapy may lead to the growth of pathogenic or antibiotic-resistant bacteria in the gut.

Aims: The study aimed to compare the impacts

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of H. pylori eradication with reverse hybrid therapy and bismuth quadruple therapy on the components and macrolide resistance of the gut microbiota.

Methods: H. pylori-related gastritis patients were randomly to receive either 14-day reverse hybrid or 14-day bismuth quadruple therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3-V4 region of the bacterial 16S rRNA gene in fecal specimen was amplified by polymerase chain reaction and sequenced on Illumina Miseq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed.

Results: Reverse hybrid therapy (n=12) resulted in decreased relative abundances of Firmicutes (P＜0.001) and Actinobacteria (P=0.032) and increased relative abundance of the relative abundance of Proteobacteria (P=0.002) at the end of therapy. Bismuth quadruple therapy (n=11) led to decreased relative abundances of Bacteroidetes, Actinobacteria and Verrucomicrobia (P=2.491E-05, 0.03792 and 0.034, respectively) and increased relative abundances of Proteobacteria and Cyanobacteria (P=1.28E-05 and 0.003, respectively).

Nonetheless, the relative abundances of all phyla at week 48 were not significantly different from those at baseline in both groups. At the end of eradication therapy (week 2), reverse hybrid group had a lower relative abundance of Cyanobacteria than bismuth quadruple group (0.012% vs 0.444%; P=0.034). However, there were no differences between groups in the relative abundances of any phyla at week 8 and week 48. With regard the macrolide resistance, the two patient groups had comparable amounts of fecal erm(B) gene before treatment and at week 2. However, reverse hybrid group had a higher amount of fecal erm(B) gene than bismuth quadruple group at week 8 (P=0.023). There were no differences in the amount of fecal erm(B) gene between groups at week 48.

Conclusions: Different anti-H. pylori therapies can result in different impacts on the components and erm(B) gene amount of gut microbiota during eradication therapy. The majority of changes in the components of gut microbiota during H. pylori eradication therapy can restore to initial status 1 year post-treatment.

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FEASIBILITY AND SAFETY OF ENDOSCOPIC ULTRASOUNDGUIDED FINE NEEDLE BIOPSY OF SOLID LIVER LESIONS Weng-Fai Wong2, Shih-Jhe Chen2, Yu-Ting Kuo1,2, Ming-Lun Han1,2, Chieh-Chang Chen2, Tsu-Yao Cheng2, Wei-Chih Liao2, Hsiu-Po Wang1,2 Division of Endoscopy, Department of Integrated Diagnostics Therapeutics, National Taiwan University Hospital, Taipei, Taiwan1 Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2

探討內視鏡超音波指引細針切片對於 診斷肝臟實質性病灶的可行性及安全 性 黃永輝2 陳世哲2 郭雨庭1,2 韓明倫1,2 陳介章2 鄭祖耀2 廖偉智2 王秀伯1,2 台大醫院內視鏡光學診斷暨治療中心1 台大醫院內科部2 Background: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) sampling is a safe and effective technique for diagnosis of pancreatic lesions. However, data are limited in its role in solid liver lesions.

Aims: In this study, we aim to compare the diagnostic accuracy and safety between EUSFNB, EUS-guided fine needle aspiration (EUSFNA) and trans-abdominal ultrasound (US)guided percutaneous biopsy for solid liver lesions.

Methods: The patients who underwent EUS-FNB, EUS-FNA or US-guided biopsy for diagnosis of solid liver lesions were prospectively enrolled and retrospectively analyzed. The primary outcome was the diagnostic accuracy. The secondary outcomes were the median numbers of passes required to establish a diagnosis and complication rate. The baseline characteristics between the 3 groups were compared by Fisher exact test for categorical variables and by Mann-Whitney U test for continuous variables. Statistical analyses were performed using Stata version 14 (StataCorp, Col- lege Station, TX). All tests were 2-tailed, and differences were considered significant if P＜0.05.

Results: Total ninety-five patients with solid liver

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lesions who visited National Taiwan University Hospital between December 2017 and April 2019 were prospectively recruited for this study.

Thirty patients underwent EUS-FNB, 30 patients underwent EUS-FNA and 35 patients underwent US-guided biopsy. Patient characteristics, sampling accuracy and median numbers of passes were not significantly different between the three groups. In EUS-FNB group, sensitivity, specificity and accuracy for solid liver lesions were 96.4%, 100% and 96.7%, respectively. In EUSFNA group, sensitivity, specificity and accuracy for solid liver lesions were 96.3%, 100% and 96.7%, respectively. In US-biopsy group, sensitivity, specificity and accuracy for solid liver lesions were 100%, 62.5% and 91.4%, respectively. The mean number of needle passes was 2.3±0.7, 2.1±0.8 and 2.1±0.5 in EUS-FNB, EUS-FNA and USbiopsy group, respectively. No any complications were seen among the three groups.

Conclusions: Compared to EUS-FNA and USguided biopsy, EUS-FNB can be a safe and efficient alternative method for diagnosis of solid liver lesions.

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GASTRIC NEUROENDOCRINE NEOPLASM: A RETROSPECTIVE STUDY ON CLINICAL PROGNOSIS AND SURGICAL INTERVENTION Sheng-Chieh Lin, Jin-Ming Wu, Po-Jen Yang, Po-Chu Lee, I-Rue Lai, Chiung-Nien Chen, Ming-Tsan Lin Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

胃神經內分泌腫瘤的預後與手術治療 林聖傑 吳經閔 楊博仁 李柏居 賴逸儒 陳炯年 林明燦 台大醫院外科部一般外科 Background: Neuroendocrine neoplasm (NEN) is the third common type of gastric malignancy.

While diagnostic techniques improving, the overall incidence of NEN also increased. Despite disease progression varied in patients with gastric NEN, studies focusing on prognostic factors of gastric NEN are still limited.

Aims: The aim of this study is to identify the prognostic factors and understand the role of surgical intervention.

Methods: We retrospectively included gastric NEN cases diagnosed at the National Taiwan University Hospital during January 2013 to May 2019. Pathology was classified according to 2010 WHO classification. We stratified patients by their pathology grade, tumor size, advanced status, tumor location, and distant metastasis. Using Kaplan-Meier methodology, we evaluated their overall survival (OS) and disease free survival (DFS).

Results: 31 patients were included in our study (male: 15, female: 16). Mean age was 60.6±15.2 years old. Of these patients, 15 had no specific initial symptoms. 5 patients had GI bleeding, 7 had epigastric pain, and 4 had abdominal distension. Curative resection was performed in 27 patients, in which 14 received surgical intervention and 13 patients received endoscopic resection. In pathology, there were 14 patients classified as grade 1 (G1) neuroendocrine tumor (NET), 5 as G2 NET, and 12 as G3 neuroendocrine cancer (NEC). The mean of OS was 57.7 months±5.4 months. The estimated 1- and 3-year OS rates for all patients were

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83% and 75%. Poor prognosis was observed in pathology G3 (1-year survival 54%, p＜0.001), distant metastasis (1-year survival 44%, p＜ 0.001), and tumor size＞5 cm (1-year survival 51%, p=0.002). Distant metastasis was found at diagnosis in 8 patients. Among them, surgical resection of primary tumor was performed in 5 patients, whose OS was longer than that of those who did not receive operation (mean OS 27.5 vs.

4.7 months).

Conclusions: Curative resection is the main treatment for gastric NEN. Pathology G3, distant metastasis, and tumor size＞5 cm are important poor prognostic factors. We suggested that palliative surgery may still benefit patients with distant metastasis.

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UNEXPECTED HIGHER GASTRIC POLYPS DETECTION RATE DURING SEDATIVE ENDOSCOPY Chi-Yi Chen, Ming-Tse Hsu, Tsung-Jung Tsai, Yu-Min Feng, Chien-Chung Fang, Po-Yueh Chen Division of Gastroenterology, Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan

無痛麻醉胃鏡檢查可以找到更多的胃 瘜肉 陳啟益 許銘澤 蔡崇榮 酆裕民 方建忠 陳柏岳 嘉義基督教醫院胃腸肝膽科 Background: Esophagogastroduodenoscopy (EGD) is an important tool for diagnosis of UGI disease. Peptic ulcer, GERD and gastric polyps were common abnormal findings in EGD. Sedative endoscopic examination offer good quality of examination without pain and fear.

Unexpected higher detection rate of gastric polyps was noted during sedative endoscopy recently.

Aims: To investigate the detection rate of gastric polyp, detected size of gastric polyp, detected numbers of gastric polyp, location of gastric polyp between sedation and non-sedation examination.

Methods: We collected 8923 patients who received EGD examination between January 1, 2019 and June 28, 2019 at Chia-Yi Christian hospital. There were 3865 patients received intravenous general anesthesia and 5058 patients did not sedation. The data collected included demographics (age and sex); parameters of the polyp (number, size, site); and pathology of polyp.

Results: We found that 40% of EGD examination received sedation. Good endoscopic quality resulted in more small gastric lesion detection and delicated tissue biopsy. The sedative group had significantly higher overall polyp detection rate (21.5% vs 5.7%, P＜0.001). The detected number of gastric polyps were not significant difference between two groups. Better detection of small gastric polyp (size less than 0.5 cm) was noted in sedative group. (P＜0.01) There were more gastric polyp detection at gastric body in sedative group than non-sedative group. Two GIST and two NET noted as small polyps (less than 0.5 cm) were detected in sedative group. Complete

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cold snare polypectomy were achieved with good pathological confirmation.

Conclusions: Small gastric polyp (less than 0.5 cm) located in gastric body were found to have better detection rate in sedative EGD. Complete endoscopic polypectomy with cold snare in sedative EGD were achieved to diagnosis and treat small GIST and NET. In sedative EGD, we can find more polyps, see more small tumor, and treat more early gastric lesion with cold snare polypectomy. We collected more early GIST and NET in spite of more fundic gland polyposis and hyperplasia polyp.

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THE RELATIONSHIP OF NUTRITIONAL MANAGEMENT OF ESOPHAGEAL CANCER PATIENT TO INCREASE SURVIVAL RATE Mei-Chen Chen, I-Hao Tseng, Szu-Jen Wang, Meng-Shun Sun, Hsi-Jung Chen, Ching-Yang Tsai Department of Internal Medicine and Section of Gastroenterology, Yuan’s General Hospital, Kaohsiung, Taiwan

營養介入對於食道癌存活率的提升 陳美蓁 曾逸豪 王嗣仁 孫盟舜 陳錫榮 蔡青陽 阮綜合醫院消化內科 Background: Esophageal cancer is one of the most fatal cancers worldwide. It ranked the ninth for cancer death of Taiwan in 2018. The incidence of esophageal cancer increased in these 20 years, and the age of esophageal cancer decreased. The poor nutritional status of the late stage of esophageal cancer patients is often related to the presence of cancer cachexia and tissue wasting. Malnutrition in the patient of esophageal cancer affects quality of life, worsens patient’s tolerance to chemotherapy and surgery, and accounts for lower survival.

Aims: Nutritional management included proper nutritional assessment and different ways of nutritional support. The purpose of this study is to review the nutritional status and the nutritional support of esophageal cancer patients of Yuan’s general hospital. Different nutritional intervention affected the results of the body weight and albumin level, and the survival of these patients.

Methods: We review the medical records of 71 patients with esophageal cancer patients of Yuan’s general hospital since January 2016 to December 2018. The review included the stage of the esophageal cancer, the nutritional status, and nutritional support of esophageal cancer patients of Yuan’s general hospital. The nutritional status was screening with Eastern Cooperative Oncology Group (ECOG) and Nutrional Risk Screening-2002, and others.

The nutrition management was intervened by the dietian’s evaluation and suggestion of daily calories supply. The ways of nutritional support were divided to oral feeding, nasogastric tube

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feeding, gastrostomy feeding and jejunostomy feeding. Treatment outcome and survival rate were retrospectively evaluated.

Results: With a median follow up of 15 months (range, 0-36 months), patient’s one year overall survival (OS) rate was 60.58% and the median survival time was 14.49 months. The median survival time of oral feeding was 18.73 months.

The median survival time of gastrostomy feeding was 9 months. The median survival time of jejunostomy feeding was 17.4 months. NG feeding was only three cases and two cases expired within 2 months. One case is undertreatment currently.

Conclusions: When esophageal cancer patients are unable to maintain optimal nutrition supply, various feeding tubes could be considered. The benefit of the nutritional intervention should be weighed against the possible complications, especially those with late stage disease and poor short term survival. Careful observation and clinical nutritional support are required for patients with advanced esophageal cancer patients.

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THE EFFECTIVENESS OF ESOPHAGOGASTRODUODENOSCOPY IN PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING WITHIN ACUTE CORONARY ARTERY DISEASE Chao-Feng Chang, Hsuan-Hwai Lin, Yu-Lueng Shih, Tsai-Yuan Hsieh, Hsin-Hung Huang Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

探討上消化道內視鏡介入於冠狀動脈 併消化道出血患者的預後因子 張肇丰 林煊淮 施宇隆 謝財源 黃信閎 三軍總醫院胃腸肝膽科 Background: Upper gastrointestinal tract bleeding (UGIB) is critical disease. Clinically, it should be managed immediately to prevent following adverse events. There were prior studies indicated that UGIB patients had twice risk for subsequent acute CV events. UGIB contributes to hypovolemia, hypotension, declined hemogolobulin level and decreased oxygen-carrying capacity, and it further leads to myocardial ischemia. Hence, the impact of UGIB is great in acute CV events. There is a dilemma about utility of esophagogastroduodenoscopy (EGD) with acute cardiovascular event having overt UGIB can present a challenge.

Aims: We aimed to analyze the effectiveness of esophagogastroduodenoscopy in patients with upper gastrointestinal bleeding within acute coronary artery disease.

Methods: Our study was a retrospective cohort design. We recruited selected 35382 individuals in NHIRD between 2000 and 2013 in Taiwan. The inclusion criteria of acute Coronary artery disease receiving blood transfusion in case group were confirmed by ICD-9-CM 203.0. We excluded 1870 individuals diagnosed as MM before index date, those patients sustained mortality before tracking, those patients’ age lower than 20 years old and unknown gender. The selected cases were divided into receiving EGD and not receiving EGD in one month.

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Results: In our study, we analyzed the Length of hospital stay, Mortality rate and recurrent episode of acute CAD. There was no significant difference in mortality in one year (p=0.433), and there was no significant difference in CAD recurrence in one month (p=0.782). However, there was obviously significance of the length of hospital stay (p＜ 0.001).

Conclusions: Our study revealed that the utility of EGD in acute CAD patients with overt UGIB was available in clinical practice. It resulted in fewer deaths and fewer recurrent CAD episodes.

As to those patients with acute CAD combined with overt UGIB, timely EGD was considered, and it lowers the complication and improve the patient’s outcome. The length of hospital stay was remarkably shorter, and it may decrease the payment of hospitalization. However, risk stratification is important, must explained the possible risks such as acute MI, arrhythmia or death to the patient or family before examination

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ENDOSCOPIC RESECTION FOR GASTRIC SUBEPITHELIAL TUMOR ORIGINATING FROM THE MUSCULARIS PROPRIA LAYER – A SINGLE CENTER EXPERIENCES Chi-Ying Yang1, Chun-Fu Ting1, Wen-Hsin Huang1, Chun-Lung Feng2, Cheng-Kuo Chen3, Wang-De Hsiao1 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan3

內視鏡切除源自固有肌層的胃黏膜下 腫瘤—一個醫學中心的經驗 楊其穎1 丁俊夫1 黃文信1 馮俊龍2 陳政國3 蕭望德1 中國醫藥大學附設醫院消化系1 中國醫藥大學新竹附設醫院肝膽腸胃科2 亞洲大學附設醫院肝膽腸胃科3 Background: Gastric subepithelial tumor was usual incidentally found during endoscopy. The subepithelial tumor was considered benign, but gastrointestinal stromal tumors (GISTs), neuroendocrine tumors, glomus tumor and metastatic tumors had malignancy potential, especially originated from muscularis propria (MP) layer. The endoscopic ultrasound was used to evaluate SETs. It was still a challenge to diagnose the hypoechoic SETs originating from MP layer by endoscopic ultrasound. Removal of gastric SETs and histopathologic confirmation should be considered when malignant potential tumor was suspected.

Aims: To evaluate and compare the pathology of gastric hypoechoic subepithelial tumor originating from the MP layer.

Methods: A retrospective analysis was performed from April 2013 to April 2019. One hundred thirty-seven patient with hypoechoic gastric subepithelial tumor originated from MP by endoscopic ultrasound in our hospital

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and performed endoscopic submucosa dissection (ESD) were enrolled. Tumor location, characteristics, complete resection rate were analyzed.

Results: One hundred thirty-seven patients with 140 lesions were eligible for inclusion in this study. The mean age of the patients was 56.4 (range 26 - 88) years, and the male/female ratio was 0.67:1 (men: 51; female: 76). The mean tumor size was 16.89±10.54 mm (range 2.4 mm - 67 mm). Three patients (2.2%, 3/137) hold ESD procedure (one patient was perforation and switched to surgical resection; 1 patient was too large wound to closure; other one was hold due to rapid heartbeat). The pathology of 4 lesions were not complete analyzed due to huge tumor sizes (range 48 mm - 61 mm) and were difficult to remove totally. The gastric SETs from MP layer were most common in the body (47%, 66/140), followed by cardia (29%, 41/140), fundus (19%, 26/140), antrum (4%, 6/140) and angularis (1 %, 1/140). The pathological diagnoses were GIST (62.1%), leiomyoma (30%), Schwannoma (2.1%), heterotropic pancreas (1.4%), paraganglioma (0.7%), fibroma (0.7%). The GISTs were located at body (46%, 40/87), fundus (28.7%, 25/87), cardia (18.4%, 16/87), antrum (5.7%, 5/87) and angularis (1.2%, 1/87). Leiomyomas were located at cardia (52.3%, 22/42), body (45.2%, 19/22) and fundus (2.5%, 1/42). Eighty-four of 87 GISTs (96.6%) were successful resection and the R0 resection rate was 70.2% (59/84). The GIST less than or equal to 2 cm, the R0 resection rate was 82.3% (42/51). If the size of GISTs more than 2 cm, the R0 resection rate was 51.5% (17/33).

Conclusions: The ESD is an effective and relatively safe means for diagnosing and treating gastric SETs originating from the MP layer. Large tumor size was difficult to remove specimen. The most common gastric SETs from MP layer are GISTs and leiomyomas. The GISTs from MP layer are usually noted at body, fundus and cardia; the leiomyomas from MP layer are usually noted at cardia and proximal body. In our study, the prevalence rate of GIST and leiomyoma from MP layer were almost the same in the gastric cardia.

Low R0 resection rate (51.5%) was noted when the size of GIST was more than 2 cm. But the recurrence rate was still need to long term followup. In this study, it was retrospective, a single hospital clinical experience and needed more data to further evaluate.

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EFFICACY AND SAFETY OF THE BRAVO™ 96 HOUR PH MONITORING SYSTEM: AN EXPERIENCE OF YUAN-SHENG GERD CENTER IN TAIWAN Wen-Chieh Wu GERD Center, Yuan-Sheng Hospital, Changhua, Taiwan

96 小時無線酸鹼膠囊的有效性與安全 性：台灣員生胃食道逆流中心的經驗 吳文傑 員生醫院 Background: The Bravo™ 96 hour pH monitoring system is just available in Taiwan one year ago and still not common in hospitals. However, it is an important diagnostic test for GERD disease, especially for patients with refractory GERD symptoms.

Aims: Evaluate the efficacy and safety of the Bravo™ 96 Hour pH monitoring system.

Methods: The study included patients underwent the Bravo™ 96 Hour pH monitoring system for refractory GERD and LPR symptoms from June 2018 to June 2019 in Yuan-Sheng GERD Center in Taiwan. The primary outcome is safety including immediate or delayed bleeding and pneumonia. The second outcome is efficacy, including diagnosing fake GERD and true GERD without good medicine control.

Results: Totally 56 patients underwent the Bravo™ 96 Hour pH monitoring system were analyzed. The results are male (53.57%) and in conscious sedation procedure (100%). The post-procedure discomfort included chest pain (3.57%) and throat sore (5.35%). No immediate complication or late complication happened.

Bravo capsule early drop off (within 96 hours) is 3.57% and delayed drop out (longer than 28 days) is 1.78%. The final diagnosis is pathologic GERD (25%), esophageal hypersensitivity (3.57%) and other etiology (71.5%). All patients with a diagnosis of other etiology stop PPI medicines and surgery treatments. Manometry is arranged.

Conclusions: Bravo™ 96 Hour pH monitoring system is a safe procedure and efficient to diagnose patients presenting with refractory GERD and LPR symptom.

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OUTCOME OF ENDOSCOPIC RESECTION OF EARLY GASTRIC CANCER: OUR EXPERIENCE IN TAIPEI TZU-CHI HOSPITAL Wen-Yi Chang, Jiann-Hwa Chen, Tsung-Hsien Hsiao, Lung-Yuan Hsu, You-Chen Chao, Wei-Chih Su Division of Gastroenterology Hepatology, Department of internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan

早期胃癌經內視鏡治療之預後：本院 經驗 張文毅 陳建華 蕭宗賢 徐榮源 趙有誠 蘇偉志 台北慈濟醫院內科部胃腸肝膽科 Background: Gastric cancer is one of the most common cancers in Taiwan. Surgical resection plus lymph node dissection is standard therapy. However, surgical treat carried risk of perioperative complication and post-gastrectomy syndrome dose influence quality of life. Early gastric cancer has low lymph node metastasis rate and endoscopic resection had become treatment of choice in eastern country. Compare with surgery, endoscopic resection is a less invasive treatment and had better functional preservation of stomach. However, some studies showed patient who receive endoscopic therapy have higher recurrence and metachronous cancer risk.

Aims: To evaluate outcome of the early gastric cancer patients who received endoscopic therapy at Taipei Tzu Chi Hospital.

Methods: We reviewed patient’s data who received endoscopic resection of early gastric cancer between June 2011 and Oct. 2018 in Taipei Tzu Chi Hospital. Demographic data including age, sex and co-mobility were recorded.

We also collected pre-resection evaluation results including conventional endoscopic finding (lesion size, localization, morphology), pathology, H. pylori status, computerized tomography and endoscopic ultrasound. Endoscopic resection method, peri-operative complication and pathology staging were recorded. Follow-up endoscopy and CT were scheduled within 6 months after ESD then depended on the decision of attending physician. Survival status and

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endoscopic finding were checked by medical record and telephone tracking.

Results: Twelve early gastric cancer including 9 males and 3 females received endoscopic treat between June 2011 and Oct. 2018. The age is 66.7±9.5 with range from 48-82 years old. Eight patients had underlying co-morbidity (5 hypertension, 4 diabetes, 2 coronary arterial disease, 1 hepatitis B, 1 hepatitis C) and one of the patients had history of breast cancer. Six patients had H. pylori infection and two were eradicated before. Pre-treat pathology were at least severe dysplasia. The clinical stages of the cases were T1N0, except one suspected T2 lesion which was noticed by EUS. ESD was used as endoscopic tumor resection method to all 12 lesions. Eleven of 12 lesions were en-bloc resected. Post ESD pathology results were in curative criteria designed by Japan Gastroenterological Society except one T2 lesion. The patient with deep tumor invasion refused gastrectomy. We follow up clinical condition 46.3±29.9 month (range 7-91).

All cases were alive except one patient died due to ampulla of Vater cancer 32 months after ESD. There was no local recurrence/ metachronous after ESD by endoscopic follow up 35.2±23.4 months (max 79 months).

Conclusions: Our study shows good disease free and recurrent free survival for patients with early gastric cancer who was treated by endoscopic tumor resection. The risk of metachronous lesion was low with the max duration of endoscopic follow 71 months. Endoscopic treatment of early gastric cancer can maintain the quality of life after treatment while maintaining the effectiveness of cancer treatment.

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DRASTIC CHANGES OF HELICOBACTER PYLORI ERADICATION RATE – RESULTS OF TREATMENT FROM A GENERAL HOSPITAL AT CENTRAL TAIWAN Kuan-Fu Liao1,2,3, Sung-Mao Tsai1, Wai-Keung Chow1, Chung-Yi Lin1,2, Chi-Ming Lin1, Yu-Hung Kuo3 Division of Gastroenterology and Hepatology, Department of Medicine, Taichung Tzu Chi Hospital, Taichung, Taiwan1 College of Medicine, Tzu Chi University, Hualien, Taiwan2 Department of Research, Taichung Tzu Chi Hospital, Taichung, Taiwan3

and levofloxacin one week and two weeks. The outcome measure was negative of urea breath test (UBT) 4 to 6 weeks after treatment.

Results: The first line triple therapy success rate were 83.80% in one week regimen and 88.80% in two weeks regimen (P=0.036). The second line triple therapy success rate was 86.4% in one week regimen and 88.0% in two weeks regimen (P=0.4).

Conclusions: Two weeks of first line triple therapy regimen was effective and better than one week. But the same effective as two weeks and one week in the second line triple therapy.

劇變中的幽門桿菌根除率—一中部醫 院的治療結果 廖光福1,2,3 蔡松茂1 周偉強1 林忠義1,2 林志明1 郭育紅3 台中慈濟醫院內科部胃腸肝膽科1 慈濟大學醫學系2 台中慈濟醫院研究部3 Background: For the last two decades, the recommended treatment for Helicobacter pylori (H. pylori) eradication is the standard triple therapy (proton pump inhibitor, combined with clarithromycin and amoxicillin or metronidazole).

The efficacy of these triple regimens has decreased lately to rates lower than 70%, due to H. pylori resistance to key antibiotics, mainly clarithromycin, but also metronidazole and levofloxacin.

Aims: Prospective evaluation of H pyloric eradication rates with different regimens and duration.

Methods: This is a prospective phase IV randomized controlled study conducted From May. 2016 to June. 2019 at a mid Taiwan general hospital. Enrolled were 986patients who had a positive rapid urease test (CLO test) or histology on endoscopic biopsy. Patient were randomized to 2:1 first line triple therapy combining proton pump inhibitor (PPI), amoxicillin, clarithromycin one week and two weeks. Patients who failure to first line triple therapy were randomized to second line triple therapy combining with PPI, amoxicillin

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THE EFFICACY OF CONTRASTENHANCED HARMONIC ENDOSCOPIC ULTRASOUND ON DETECTION OF EXISTENCE OF MALIGNANCY IN THE AMPULLARY TUMORS Yen Wan1, Hsuan-Ho Lin1, Yu-Ting Kuo1,2, Kuan-Chih Chen4, Chih-Hsiang Chen1, Wei-Yuan Chang1, Po-Yen Jung1, Ko-Han Chao1, Shih-Che Chen1, Wei-Chih Liao1, Tsu-Yao Cheng1,3, Chieh-Chang Chen1, Ming-Lun Han2, Hsiu-Po Wang1,2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan1 Department of Intergrated Diagnostics and Therapeutics, Division of Endoscopy, National Taiwan University Hospital ,Taipei, Taiwan2 Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan3 Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan4

對比顯影劑內視鏡超音波對於偵測壺 腹腫瘤惡性存在有效性之研究 萬儼1 林宣合1 郭雨庭1,2 陳冠至4 陳至翔1 張為淵1 戎伯岩1 趙珂漢1 陳世哲1 廖偉智1 鄭祖耀1,3 陳介章1 韓明倫2 王秀伯1,2 國立臺灣大學醫學院附設醫院內科部1 國立臺灣大學醫學院附設醫院綜合整療部內視鏡 科2 國立臺灣大學醫學院附設醫院檢驗醫學部3 亞東紀念醫院內科部4 Background: Ampullary tumors are increasingly diagnosed due to advances in imaging technology. Endoscopic papillectomy has been applied on ampullary adenoma without malignancy and without bile and pancreatic duct invasion. However, there is a high percentage of malignancy unable to be acquired before resection. Several modalities have been proposed for increasing the predictive rate of malignancy,

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including PET scan, EUS elastography and contrast enhanced harmonic EUS (CEH-EUS).

Aims: We conducted a retrospective study to check the efficacy of differentiate non-malignant from malignant ampullary tumors by CEH-EUS. Methods: Between April, 2018 to June, 2018, total 20 patients who had ampullary tumor and received CEH-EUS with final pathology result (either surgical or endoscopic papillectomy) were enrolled. CEH-EUS was performed during the EUS staging of ampullay tumors. The contrast used was Sonazoid with injection dose 0.5 cc for each checking and observation time was 2 minutes under setting of ME2, Olympus UCT260 echoendoscope. The CEH-EUS pattern was graded as hypoenhancement and Iso-/ hyperenhancement. The pattern of CEH-EUS was compared between non-malignant and malignant ampullary tumors. T-test and Chi-Square were used for statistical analysis by SPSS software (Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc).

Results: 16 patients (6 males) were ampullary adenocarcinoma and the other 4 patients (4 males) were non-malignant lesions. The mean age of malignant group was 69.7 years old and of non-malignant group was 66.3 years old (p=0.523). The mean tumor size of malignant group was 2.25 cm and of non-malignant group was 1.84 cm (p=0.279). Hypoenhancement of the ampullary lesions under CEH-EUS were shown on 8 of 16 patients (50%) with malignancy and 1 of 4 patients (25%) with non-malignant lesions.

There was no statistically significant difference between CEH-EUS enhancement pattern between ampullary non-malignant and malignant tumors (Fisher’s Exact Test, p=0.591).

Conclusions: There was no difference in CEH-EUS enhancement pattern between ampullary non-malignant tumors and ampullary adenocrcinoma. Considering the small sample size, more cases to confirm the final conclusion is needed.

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THE CLINICAL FEASIBILITY AND OUTCOMES OF ENDOSCOPIC FULL THICKNESS RESECTION WITH LAPAROSCOPIC SURGERY FOR LOCALIZED DUODENAL NEUROENDOCRINE NEOPLASMS Jae Yeong Cho, Dae Young Cheung, Jin Il Kim, Soo-Heon Park Department of Internal medicine, The Catholic University of Korea College of Medicine, Seoul, Korea

experienced perforation and underwent surgery.

Tumor recurrence and metastasis were not reported during the study period in all patients.

Conclusions: EFTRLS provides a precise and secure safety margin of tumor resection and abolishes the risk of uncontrolled bleeding and perforation. EFTRLS has the advantage in the oncological completeness and patient safety over either endoscopic resection alone or surgery alone.

Background: The duodenal neuroendocrine tumors (dNETs) are arising from the cell of the mucosal layer and often small and confined to the superficial layer. Surgery and endoscopic resection are both considered appropriate; however, there are critical hurdles to both modalities in real practice. Laparoscopic surgery has a difficulty to determine precise tumor location, and endoscopic resection has high risks for bleeding, perforation, and incompleteness.

Aims: In our study, we compared the treatment outcomes of endoscopic full-thickness resection assisted laparoscopic surgery (EFTRLS).

Methods: The electronic medical record database was reviewed at a university hospital (Yeouido St. Maryâ&#x20AC;&#x2122;s Hospital), Seoul, Korea. A total of 36 patients were found to be diagnosed during the last 15 years, from Jan 2004 to Dec 2018.

Results: Among the 36 patients with dNETs, 12 were excluded, follow-up loss (3), transfer-out (2), treatment refusal (2), invisible after forceps biopsy (2), poorly diďŹ&#x20AC;erentiated histology (2), and the presence of metastatic lesion (1). Twentyfour patients who showed well-differentiated histology, less than 2 mitosis per 10 HPF and less than 3 Ki-67 index, underwent excision of tumors.

Fifteen were treated with endoscopic resection, and 4 were with surgery. Five were with EFTRLS. Resection margin involvement was none in the EFTRLS group compare to other single modality groups (0% [0/5 cases] vs 13% [2/15 endoscopic resection] vs 25% [1/4 surgery only]). One endoscopically treated patient had a macroscopic residual tumor and needed additional surgery.

Two patients of endoscopic resection group

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PROPHYLACTIC CLIPPING FOR THE PREVENTION OF DELAYED COMPLICATION AFTER ENDOSCOPIC RESECTION FOR SUPERFICIAL NON-AMPULLARY DUODENAL TUMOR Oong-Hee Shin1, Jee-Young An1, Byung-Wook Kim1, Jae-Myung Park2, Tae-Ho Kim3, Jae-Sin Lee3 Department of Internal Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Korea1 Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea2 Department of Internal Medicine, Bucheon St Mary’s Hospital, The Catholic University of Korea, Bucheon, Korea3 Background: Although endoscopic resection (ER) has been accepted as a standard treatment modality for superficial non-ampullary duodenal tumor (SNADT) recently, it can cause adverse events such as perforation and bleeding.

Aims: The effect of prophylactic mucosal closure after ER is controversial. The aim of this study was to investigate the efficacy of prophylactic clipping for the prevention of delayed complications.

Methods: We retrospectively reviewed medical records of patients who underwent ER for SNADT from 4 centers. Patients were divided into 2 groups, immediate clipping group (ICG) vs. no clipping group (NCG). Baseline characteristics and factors associated with delayed complications such as size of the lesion, tumor location, histologic types, and co-morbidities were compared between the two groups. Statistical analysis was performed using SPSS. Results: A total of 99 lesions from 99 patients were included in this study. Six patients underwent ESD and 93 patients underwent EMR. 52 patients were allocated into ICG and 47 patients were allocated into NGC. Delayed bleeding occurred in 1 patient (1.9%) and delayed perforation occurred in 1 patient (1.9%) among ICG. Delayed bleeding occurred in 8 patients (17.0 %, p=0.012) and delayed perforation occurred in 3 patients (6.4%,

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p=0.343) in NCG. Delayed perforation were managed by laparoscopic simple closure and delayed bleeding were managed by endoscopic hemostasis. There was no procedure related death.

Conclusions: Although prophylactic clipping showed a tendency of low complication rates, further studies with prospective design is anticipated.

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P.137 N O R M AT I V E VA L U E S F O R 2 4 - H O U R S AMBULATORY ESOPHAGEAL IMPEDANCE AND PH MONITORING IN HEALTHY MALAY COHORT

Mohammad Majharul Haque1, Thung Su Fui2, Lee Yeong Yeh3 Dhaka medical college, Dhaka, Bangladesh1 Hospital University Sains Malaysia, kelantan, Malaysia2 Hospital University Sains Malaysia, Kelantan, Malaysia3

for percentage of total time with pH <4 and DeMeester score were 5.1 and 10.3 respectively.

Conclusions: The number of total reflux episodes in the Malay population was similar to that in the Western population but weakly acidic refluxes were predominant in Malay population unlike acidic refluxes in Western population. Gender, BMI and region of study made difference in impedance parameters but not in pH parameters.

Background: Current normative values for 24-hours ambulatory esophageal impedance and pH have been derived from Western populations.

Normative data for Asian population is currently lacking. Moreover, no data are available regarding factors influencing these values.

Aims: 1. To determine normative values of esophageal impedance and pH in Malay population. 2. To evaluate factors affecting these values.

Methods: We conducted a cross sectional study where healthy Malay volunteers of more than 18 years old with no significant present and past medical history were enrolled in two university hospital of Malaysia( HUSM and HUKM) using GERDQ questionnaire. Data were obtained using the Multi-channel Intra-luminal Impedance Ambulatory System [Sandhill Scientific and Medical Measurement System (MMS)].

Results: Eighty three (28 males, 55 females) healthy Malay volunteers were recruited for the study. 95th percentile value for the total number of impedance reflux events over 24 hours was 107, of which 31 % events were acid-related and 69 % events were non-acid related. Impedance reflux events were more in the upright compared to supine position (85 vs 18) and weakly acidic refluxes were predominant. Male had significantly higher total reflux episodes than female (56.5 vs 39, p=0.007) while overweight participants had significantly higher total reflux and weakly acidic reflux episodes. Participants from urban hospital (HUKM) had significantly higher total reflux and acidic reflux than those from rural hospital (HUSM). The 95th percentile values

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REAL-WORLD MANAGEMENT OF LOSS OF RESPONSE TO BIOLOGICS IN INFLAMMATORY BOWEL DISEASE Wei-Chen Lin1, Chen-Wang Chang1, Ming-Jen Chen1, Tzu-Chi Hsu2, Horng-Yuan Wang1 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan1 Division of Colon and Rectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan2

真實世界在發炎性腸炎疾病對生化製 劑喪失效果之處置 林煒晟1 章振旺1 陳銘仁1 許自齊2 王鴻源1 台北馬偕紀念醫院胃腸肝膽科1 台北馬偕紀念醫院大腸直腸外科2 Background: Biological therapy has revolutionized the treatment of inflammatory bowel disease (IBD). In practice and clinical trials, 20–40% of IBD patients do not show clinical response or loss of response (LOR) to biologics therapy.

Aims: Assessment of drug levels and antibodies have been proposed for managing LOR. However, therapeutic drug monitoring is not available in Taiwan.

Methods: A retrospective analysis of data on IBD patients suffering from LOR to biologics at the MacKay memorial hospitals was conducted. The definition of LOR was those patients who did not respond to the induction therapy or lose response during the biologic treatment.

Results: There were 14 patients suffered from LOR under biologics therapy. Four patients were female and mean age was 42 year old (range 21-73). Four patients were ulcerative colitis (UC) and 8 patients were Crohn’s disease (CD).

Adalimumab was the most common used and LOR agent (87.2%; 85.7%, respectively). Two patients (14.3%) were primary non-responder.

During biologic therapy, the rate of combination medication of steroid, immunomodulator and mesalazine were 42.9%, 42.9% and 57.1%. For management of LOR, adding steroid (57.1%) was the most common method, following by adding mesalazine (21.4%). In UC patients, the common

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method was add-on steroid (60%). Among CD patients, adding steroid (66.7%) and mesalazine (33.3%) were two common methods.

Conclusions: Despite advancements of IBD therapy in the last decade, a substantial number of patients are not fully responsive to treatment or lose efficacy over time. Optimization of biologic therapy in conjunction with other medication in IBD patients with LOR is an important issue in the real-world practice.

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COMBINING ALVARADO AND ULTRASOUND TO DIAGNOSE ACUTE APPENDICITIS Chen-Ta Yang, Wei-Wen Su Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

運用 Alvarado Score 和超音波診斷闌 尾炎

performance to rule out appendicitis if score is less than 3 and to diagnose appendicitis if higher than 7. Futher CT scan is still needed if intermediate Alvarado score and inconclusive sonographic report.

Conclusions: Ultrasound showed 80% diagnostic accuracy when Alvarado score ranging 3~7. Futher CT scan is still needed if intermediate Alvarado score and inconclusive sonographic report.

楊承達 蘇維文 彰化基督教醫院胃腸肝膽內科 Background: Sonogram was utilized to diagnose acute appendicitis but carried lower sensitivity and inconclusive findings when comparing to CT scan.

Aims: Combining Alvarado score and ultrasound finding may be a good way to diagnose acute appendicitis.

Methods: Sonographic examination was applied to the patients who clinically suspected as acute appendicitis (but low or intermediate likelihood) by the ED physicians. CT scan was applied as first modality if highly suspicious of acute appendicitis.

The sonographic findings were categorized to 4 groups (category 1: normal appendix, category 2: partial or poor visualization of appendix without secondary signs, category 3: partial or poor visualization of appendix with secondary signs, category 4: definite appendicitis). Appendectomy was performed if appendicitis was confirmed by image study (sonographic category 4, or diagnosed by CT or MRI scan). Alvarado score were calculated retrospectively.

Results: From April/01/2017 to November/30/2018, total 92 patients underwent ultrasound as the initial image modality for suspected acute appendicitis.

There were 26 men (28%) and 66 (72%) women (14 pregnancy) with mean age 39.8 years-old (range: 20-89 years). The median of Alvarado score were 4 (range 2-7) for patients without appendicitis and 5 (range 3-8) for histologically proved appendicitis.

The CT/MRI scan was peformed in 35% of patients.

The diagnostic accuracy of ultrasound is 80% (sensitivity 85%, specificity 80%, NPV 97% and PPV 41%). There was limited value of Alvarado score if the score was ranging from 3 to 7 but good

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GASTROINTESTINAL ADVERSE EVENTS-INDUCED BY SODIUM POLYSTYRENE SULFONATE (KAYEXALATE) AND CALCIUM POLYSTYRENE SULFONATE (KALIMATE) USE: A LITERATURE REVIEW Yi-Hua Wu1, Jen-Wei Chou1, Tsung-Wei Chen2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Department of Pathology, China Medical University Hospital, Taichung, Taiwan2

Sodium Polystyrene Sulfonate （Kayexalate 順鉀美散）and Calcium Polystyrene Sulfonate（Kalimate 加 利美粉）所引發的腸胃道之副作用 吳宜樺1 周仁偉1 陳宗偉2 中國醫藥大學附設醫院肝膽腸胃內科1 中國醫藥大學附設醫院病理科2 Background: Hyperkalemia is a common electrolyte adverse event in patients with chronic kidney disease and can result in fatal cardiac arrhythmias. Sodium polystyrene sulfonate (Kayexalate) is a cation-exchange resin that is widely used in treating hyperkalemia. It exchanges sodium for potassium in the large bowel to promote potassium loss in the stool.

But, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Calcium polystyrene sulfonate (Kalimate), an analogue of kayexalate, is also used to treat hyperkalemia clinically. However, only a few cases of Kalimate-induced gastrointestinal tract injuries have been reported in the literature.

Aims: The aim of this study was to investigate the gastrointestinal adverse events treated by Kayexalate and Kalimate.

Methods: We systematically reviewed eligible case reports of gastrointestinal adverse events associated with Kayexalate and Kalimate use from the PubMed. The age, sex, symptoms, location of gastrointestinal injuries and risk factors of these patients were analyzed.

Results: Sixteen case reports and case series describing 78 cases of gastrointestinal adverse

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events-induced by Kayexalate and Kalimate use were identified (Kayexalate use: 73 cases; Kalimate: 5 cases). There were 54 preparations containing sorbitol (54/78, 69.3%), and 24 preparations without sorbitol (24/78, 30.7%) in these cases. Among patients who experienced gastrointestinal side effects, the mean age was 58.45±16.18 years (ranging from 18 years to 91 years). Regarding the sex, 52.6% of all patients were male. In the predisposing factors of hyperkalemia: 74.3% had a history of kidney disease (chronic kidney disease or end-stage renal disease on dialysis), 14.1% of patients had a prior solid organ transplant, and 23.0% had recently undergone an operative procedure. The mean usage time of Kayexalate and Kalimateinduced gastrointestinal adverse events was 5.4 days Only ten patients received Kayexalate or Kalimate for more than 1 month. The route of administration was administered via the oral route in 91% of cases and via the rectal route in 30.7% of cases. The presenting gastrointestinal symptoms were abdominal pain and distension (61.5%), gastrointestinal bleeding (35.8%), diarrhea (15.3%), and nausea and vomiting (7.6%). The colon was the most common involved site of the gastrointestinal tract (70.5%), followed by the small intestine (20.5%), sigmoid/rectum/ anus (15.3%), cecum (8.9%), stomach (6.4%), and the esophagus (3.8%). Histopathologic findings associated with sodium polystyrene sulfonate or use were necrosis (53.8%) of the bowel wall, ulceration (52.5%), perforation (11.5%), and hemorrhagic duodenitis (1.2%). Kayexalate or Kalimate crystals were histopathologically proven in 92.3 % of all patients. Mortality was reported in 26.9% of these cases due to gastrointestinal injuries.

Conclusions: Kayexalate and Kalimate use, both with and without sorbitol, may be associated with fatal gastrointestinal injuries. The predisposing factors are uremia, post-operation and transplantation. The most common site of Kayexalate or Kalimate-induced gastrointestinal injuries is the colon, followed by the small bowel, stomach and esophagus. Therefore, physicians should be carefully to assess the patient’s bowel motility, history of medications, comorbidity and surgery before prescribing Kayexalate or Kalimate for the management of hyperkalemia, particularly in patients with end-stage renal disease.

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RESULTS FROM 10 YEARS’ EXPERIENCE OF SINGLE BALLOON ENTEROSCOPY IN A REGIONAL HOSPITAL Hung-Da Chen1, Jiann-Hwa Chen1,2 , Tsung-Hsien Hsiao1, Wei-Chih Su1, Jueng-Yuan Hsu1,2, You-Chen Chao1,2 Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan1 School of Medicine, Tzu Chi University, Hualien, Taiwan2

單氣囊小腸內視鏡，台北慈濟醫院十 年經驗 陳泓達1 陳建華1,2 蕭宗賢1 蘇偉志1 徐榮源1,2 趙有誠1,2 台北慈濟醫院腸胃科1 慈濟大學醫學系2 Background: The invention of capsule endoscopy (CE) increased the need for study of small bowel disease. However, the application of CE was limited in several aspects, such as inability to take tissue sample and handling of this device. The single balloon enteroscopy (SBE) system was launched in 2007. SBE has been proved to be a novel modality for diagnosis and treatment for small bowel diseases.

Aims: The aim of the study was to evaluate the performances, diagnosis yield rate, and complications of SBE in a regional hospital.

Methods: Retrospective analysis of all SBE procedures during a 10 years period from July of 2009 to June of 2019 in Taipei Tzu Chi Hospital, a regional hospital in Northern Taiwan. Data was collected from electronic medical records and endoscopy records. All patients who underwent SBEs included in the analysis. Written informed consents were obtained before SBEs. SBEs were carried out using an Olympus enteroscope (SIF-Q260) and single balloon splinting tubes (Olympus SBST-1) by three endoscopists. All procedures were performed under deep sedation or conscious sedation. Patients and procedures characteristics were recorded. Depth of insertion was recorded according to endoscopy report as anatomic regions. Immediate complications were identified from the endoscopy report and nursing

records; delayed complications were identified by medical records as admissions within 30 days after procedures. The study was approved by IRB of Taipei Tzu Chi Hospital.

Results: A total of 28 SBE procedures were performed during the study period; seventeen procedures were antegrade and eleven were retrograde. Twenty-one patients underwent SBE: twelve patients were women and nine patients were men. One patient underwent three SBE procedures, and five patients underwent two SBE procedures, and others underwent one. The clinical indications of SBEs: mostly was obscure GI bleeding (OGIB), in twenty-three procedures.

Other indications included unexplained abdominal pain, in four procedures; chronic diarrhea, in one procedure. None of these patients had capsule endoscopy exam before SBE. The diagnostic rate was: twelve out of twenty-eight procedures: 42.8%. In twenty-three SBE procedures for OGIB, four procedure had spotted bleeding sites or lesions with stigmata of recent hemorrhage; all of them underwent hemostasis procedures, three succeeded and one failed; two procedures identified small bowel submucosa tumors with ulcers, and later laparoscopic surgery was performed: tumors pathology proved to be gastrointestinal stromal tumor, GIST. Immediate complication developed in only one patient, who developed acute respiratory failure after the procedure (antegrade SBE). None had delayed complication.

Conclusions: In our experience, SBE appears to be a relatively safe and efficient modality for diagnosis and treatment of small bowel diseases.

Careful examinations and detail explanation before procedure is needed especially in patients in old age.

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BENEFIT OR RISK FOR FOOD ALLERGY IN VEGETARIAN DIET? Chih-Kang Huang 1, Shih-Kuan Li 1,3, Ying-Chi Wong1, Zhe-Ying Liu1,2, Tzee-Chung Wu1, Ching-Feng Huang1 Division of Pediatric Gastroenterology Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan2 Department of Pediatrics, Yonghe Cardinal Tien Hospital, New Taipei, Taiwan3

素食者減少食物過敏或增加風險？ 黃治綱1 李士寬1,3 黃映齊1 劉喆瑩1,2 吳子聰1 黃清峯1 臺北榮民總醫院兒童醫學部兒童胃腸科1 臺北醫學大學– 北醫．萬芳醫院小兒科2 財團法人天主教永和耕莘醫院小兒科3 Background: Intake of vegetarian diet is common in Taiwan. Prevalence of food allergy is increasing gradually in these decades. Symptoms of food allergy in vegetarian were not elucidated previously.

Aims: The aim of our study was to evaluate benefit or risk of food allergy in vegetarians.

Methods: This is a nationwide, cross-sectional, randomized questionnaire survey conducted in 2012. Atopic symptoms of vegetarians (including vegans and lacto-ovo-vegetarains) and omnivores were analyzed.

Results: Total 9,160 questionnaires were enrolled. In the respondents, 280 persons were vegetarians (3.06%). Among the vegetarians, 27.86% of them claimed history of allergic symptoms. Meanwhile, 26.41% out of the omnivores had history of atopic symptoms.

Vegetarians had more frequent allergic symptoms in gastrointestinal tract including diarrhea and abdominal pain (16.67% & 11.54%) than those had omnivorous diet (14.54% & 8.06%, respectively). In addition, vegetarian also had more complaints for respiratory symptoms for allergy including sneezing and rhinorrhea (30.77% & 20.51%) than omnivores (20.47% & 16.08%, respectively). However, vegetarian had less cutaneous lesion such as itchy and rashes (56.41% & 38.46%) than omnivores (65.11%

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& 45.46%, respectively). Furthermore, eight vegetarians (10.26%) experienced difficult of breath, which was 5.7% in omnivores. One case in vegetarian group suffered from anaphylactic shock.

Conclusions: Vegetarians did not reduce the risk for food allergy. Even, they had a little higher prevalence than those in omnivorous diet. They also had higher tendency of gastrointestinal and respiratory allergic symptoms, but less cutaneous complaints than omnivores. Severe atopy such as difficult of breath and anaphylaxis were also possible under vegetarian diet.

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CLINICAL EXPERIENCE OF PUSH ENTEROSCOPY: 15-YEAR EXPERIENCE FROM A SINGLE MEDICAL CENTER Kuo-Chang Lee, Hsu-Heng Yen, Yang-Yuan Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

push enteroscpy in our series was 43%. There is no procedure related mortality.

Conclusions: Push enteroscopy remains an important diagnostic tool in the area of deep enteroscopy with a overall diagnostic rate of 43% in our series. The data suggests push enteroscopy may be performed before deep enteroscopy as an initial investigation tool in Taiwan.

在單一醫學中心：推入式小腸鏡臨床 15 年的臨床經驗 李國彰 顏旭亨 陳洋源 彰化基督教醫院肝膽腸胃內科 Background: The small intestine is difficult to investigate because of the inability to reach by upper endoscopy or colonoscopy. Although deep enteroscopy provides higher diagnostic yield, its cost is expensive and not yet covered by the insurance system in Taiwan. Push enteroscopy can provide diagnosis and treatment for proximal small intestinal lesions.

Aims: To investigate the clinical utility of push endoscopy after the development of deep enteroscopy.

Methods: From April 2004 to June 2019, a total of 303 patients received push endoscopy in our institution during the period. We analyze the demographic information, indication, treatment, final diagnosis, diagnosis made, and complication of the endoscopic treatment in our hospital.

Results: There are 303 patients received push endoscopy in Changhua Christian Hospital. The mean age of the patients is 62 year-old. There are 174 male patients (57%), and 129 female patients (43%). The indication for enteroscopy includes occult GI bleeding (67.6%), diarrhea (2.3%), chronic abdominal pain (5.6%), GI obstruction (6.3%), suspected small bowel tumors (7.6%), suspected inflammatory bowel disease (1.6%), for evaluation for polyposis (1.6%) and others (7.3%). The diagnosis after enteroscopy include ulcers (14.2%), angiodysplasia (4.3%), diverticulum (non-Meckel’s) (8.9%), non-specific enteritis (5.6%), benign tumors (2.5%). The findings of mliagnant tumors includes GIST (3%), lymphoma (1.3%), adenocarcinoma (4.6%), metastatic (10.2%). The overall diagnostic rate of

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THE CLINICAL CHARACTERISTICS OF SMALL BOWEL LIPOMAS DIAGNOSED BY DOUBLEBALLOON ENTEROSCOPY: ONE SINGLE-CENTER EXPERIENCE Gin-Shen Su1, Chia-Hsi Chang1, Ken-Sheng Cheng 1, Tsung-Wei Chen2, Jen-Wei Chou1,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Department of Pathology, China Medical University Hospital, Taichung, Taiwan2 Taiwan Association for the Study of Small Intestinal Diseases3

經由雙氣囊小腸鏡診斷之小腸脂肪瘤 臨床分析：一醫學中心之經驗 舒敬軒1 張家熙1 鄭庚申1 陳宗偉2 周仁偉1,3 中國醫藥大學附設醫院內科部消化系1 中國醫藥大學附設醫院病理部2 台灣小腸醫學會3 Background: Gastrointestinal (GI) lipomas are benign, usually single, slowly growing subepithelial tumors. They are most commonly found in the colon, but it can also be found in the esophagus, small bowel, and very rarely in the stomach. Many studies have recommended that endoscopic treatment of GI lipomas is an effective alternative to surgical resection. However, all these studies either involve a small series of patients or only have experiences of lipomas in the upper GI or lower GI tract. Thus, the experience is still lacking in treating small bowel lipomas.

Aims: Our present study aimed to share our experience, and assess the efficacy, safety and short-term follow-up prognosis of small bowel lipomas diagnosed by double-balloon enteroscopy.

Methods: From 2007 to 2018, we retrospectively reviewed 12 patients who were diagnosed of small bowel lipomas via double-balloon enteroscopy. The age, sex, symptoms, location of lipomas, lipoma size, imaging findings before enteroscopy (capsule endoscopy, abdominal computed tomography), treatment methods, and complications of these patients were analyzed.

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Results: A total of 12 patients with small bowel lipomas were diagnosed by double-balloon enteroscopy treated in China Medical University Hospital. Regarding as for the gender, 66.7% of all patients were male. The mean age was 61.8±15.6 years (ranging from 27 years to 83 years). Only one patient (8.3%) was below 40 years, 25% patients were between 40-60 years, and 66.7% patients were above 60 years.

Regarding as for the enteroscopic indications: 66.7% patients had suspected small bowel bleeding, 33.3% patients had suspicious small bowel tumors, 16.7% patients had small bowel mechanical obstruction, and 8.3% patients had unexplained abdominal pain. The location of small bowel lipomas: 16.6% patients were found in the duodenum, 41.7% patients in the jejunum, and 41.7% patients in the ileum. The mean size of small bowel lipomas was 2.5 cm; 46.2% of lipomas were less than 2.0 cm in size, 7.6% of lipomas were between 2.0-3.0 cm in size, and 46.2% of lipomas were larger than 3.0 cm in size. In the analysis of imaging studies before enteroscopy: capsule endoscopy showed 100% detection rate (4 out of 4), abdominal computed tomography showed 57.1% detection rate (4 out of 7). In the treatment methods: one patient (1/12, 8.3%) received conservative treatment, ten patients (10/12, 83.4%) received endoscopic resection, and only one patient (1/12, 8.3%) received surgical resection. None of the patients had complications after endoscopic resection or surgical resection (perforation, bleeding or sepsis).

Conclusions: Our study demonstrated that lipomas were the most common benign tumors of the small bowel. Male patients accounted for the majority of all small bowel lipomas. GI bleeding is the major presentation of symptomatic small bowel lipomas, especially when the small bowel lipomas were greater than 3.0 cm in size. We recommend that endoscopic treatment of small bowel lipomas can be a safety and effective alternative to surgical resection.

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INTESTINAL MALROTATION CAUSED BY LADD’S BAND IN ADULTS: A SYSTEMIC REVIEW IN THE LITERATURE Jia-Hung Ma1, Li-Ying Huang1, Jen-Wei Chou2 Department of Education, China Medical University Hospital, Taichung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2

由 Ladd’s Band 引起之成人腸道轉位 異常：文獻病例之回顧與探討 馬嘉宏1 黃俐穎1 周仁偉2 中國醫藥大學附設醫院教學部1 中國醫藥大學附設醫院內科部消化系2

(92%). In imaging examinations, fifteen patients (15/25, 60%) were diagnosed by abdominal computed tomography, but no patient was diagnosed by esophagogastroduo-denoscopy.

Two patients (2/25, 8%) received conservative treatment because of no symp-toms. Laparotomy was performed in nineteen cases (19/25, 76%), laparoscopy in 4 cases (4/25, 16%). Twentyfour cases experienced resolution of symptom and only one case ex-pired after surgical management.

Conclusions: From our present reviewing study, intestinal malrotation should be considered in patients with abdominal pain and sign of obstruction. Plain abdominal radiography should be per-formed first. We suggested laparoscopic Ladd’s procedure for adult patients with intestinal malrotation caused by Ladd’s band. The longterm follow-up after surgery is needed.

Background: Intestinal malrotation caused by Ladd’s band is a rare event in adult patients.

Most patients with this disease may have acute obstruction or chronic abdominal symptoms.

Ladd’s pro-cedure is the first choice to relieve symptoms and the patients have good prognosis after surgical treatment.

Aims: The aim of this study was to investigate the clinical characteristics, treatment methods, and treatment outcomes of published cases in the literature and our case report.

Methods: We present a case of a 47-year-old female presenting with tarry stool for 2 weeks in our hospital. Intestinal malrotation caused by Ladd’s band was incidentally diagnosed by abdominal computed tomography, small bowel series, and capsule endoscopy. Conservative treatment was performed because of no abdominal pain or vomiting. Moreover, we also searched case reports in PubMed using the following keywords: “intestine malrotation” AND (“Ladd’s procedure” OR “Ladd’s band”). The definition of adult patients is equal or greater than 18 years old.

Results: Twenty-six adult patients (14 males, 11 females) with intestinal malrotation caused

by Ladd’s band, including our case report and the previous published studies, were enrolled in our present study. The mean age of all patients was 38.72±15.33 years (ranging from 18 to 75 years old). Abdominal pain accounted for the most common symptoms in 23 out of 25 patients

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SHORT-TERM PROGNOSTIC FACTORS FOR ISCHEMIC COLITIS Takeo Watanabe, Shigeto Ikeda, Kenji Hirano, Hisato Maekawa Department of Gastroenterology ,Tokyo Takanawa Hospital, Tokyo, Japan Background: Ischemic colitis is a common disease, but there are few reports about not severe cases.

Aims: We evaluated the short-term prognostic factors of mild and moderate ischemic colitis.

Methods: We examined patients with ischemic colitis who were hospitalized in Tokyo Takanawa Hospital between March 2017 and April 2019. We analyzed the relationship between parameters (age, sex, WBC, CRP, bowel wall thickening (BWT), symptoms on admission), and period of not eating and hospital stay. We measured the most thickened bowel portion by CT scan. About symptoms, we divided patients into all symptoms group (All-S) with all three symptoms (blood stool, abdominal pain and diarrhea) or partial symptoms group (Partial-S). We excluded severe cases.

Results: Fifty patients with ischemic colitis were hospitalized (18 males and 32 females, mean onset age 62.9 years), and we excluded only one case who underwent a surgery during hospitalization due to bowel perforation. Age, sex, WBC and CRP were not significantly associated with period of not eating and hospital stay. The period of not eating and hospital stay correlate significantly with BWT. The coefficients of correlation were 0.424 (p=0.002) and 0.469 (p<0.001) respectively. All-S had 28 cases and Partial-S had 21 cases. The period of All-S were significantly shorter than that of Partial-S (not eating: 4.1 days vs. 6.4 (p<0.001), hospital stay: 7.8 days vs. 11.7 (p<0.001)). CRP and BWT of Partial-S were significantly worse than those of All-S (CRP:4.0 mg/dl vs. 1.1 (p=0.04), BWT: 14.6mm vs. 12.7 (p=0.04)), but there was no significant difference about WBC (p=0.473).

Conclusions: BWT was a good predictor for short-term prognosis of ischemic colitis. Patients with all symptoms had a better prognosis than patients with partial symptoms.

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STAT3 DECREASED MIR-30A-5P TO INCREASE ERRFI1 LEVELS FOR MAINTAINING COLORECTAL CANCER CELLS-DERIVED CANCER STEM-LIKE TUMORSPHERES Chun-Chia Cheng1, Yi-Fang Chang2, Bi-Ling Yang3, Hsin-Chi Lin3, Chun Yeh3, Chung-Te Hsu3, Ai-Sheng Ho3 Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan1 Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan2 Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan3

STAT3 降低 MIR-30A-5P 進而增加 ERRFI1 表現以維持大腸癌類幹細胞的 增生與形成 程俊嘉1 張義芳2 楊必玲3 林信吉3 葉淳3 許重得3 何愛生3 國家衛生研究院竹南分院分子與基因研究所1 馬偕紀念醫院血液腫瘤科2 振興醫院胃腸科3 Background: STAT3 is a transcriptional factor involving in tumorigenesis and initiation of cancer stemness property. Previously, we have demonstrated that STAT3 is a potential therapeutic target against EGFR-positive colorectal cancers (CRC) and figured out STAT3 exacerbates the survival of colorectal cancer stem-like tumorspheres (Cheng et al. Journal of Biomedical Science (2018) 25:60). However, the detailed mechanism of STAT3 on regulating gene and microRNAs (miRNAs) in the formation of CRC-derived tumorsphere is obscure.

Aims: In this study, RNAseq and small RNAseq was used to uncover the potential genes and miRNAs involving in the formation of colorectal HCT116- and HT29-derived stem-like tumorspheres that expressing LGR5 stemness marker.

Methods: STAT3 was knockdowned and analyzed consequently by RNAseq and small RNAseq for picking up the STAT3-mediated genes and miRNAs.

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Results: We found that 654 genes and 646 genes were up-regulated in HCT116- and HT29derived tumorspheres, respectively. There were 103 genes simultaneously increased in both CRC tumorspheres, including STAT3 selected as a driver gene by NetworkAnalyst (https:// www.networkanalyst.ca/). Moreover, there were 139 genes down-regulated in HT29shSTAT3 cells compared to HT29shLuc, 12 of the genes were overlapped, including NDRG1, ALDOC, BHLHE40, ATF3, C6orf223, JUND, ERRFI1, HK2, ITPKA, PLOD2, IDI1, S100A14. Among them, overexpression of NDRG1, JUND, and HK2, were associated with patient’s overall survival probability in rectum cancer according to the dataset in Kaplan-Meier plotter (http://kmplot.com/ analysis/). Furthermore, small RNAseq analysis indicated that 3 miRNAs increased in CRC tumorspheres but decreased in HT29shSTAT3 cells, including hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p. Meanwhile, miR-30a-5p decreased in CRC tumorspheres but increased in HT29shSTAT3. The hsa-miR-4521 was associated with worse overall survival probability but miR-30a-5p was associated with better overall survival probability in patients with rectum cancer. In addition, ERRFI1 was the miR-30a5p target according to comparative analysis from TargetScan (http://www.targetscan.org/vert_72/), that participated in cell proliferation.

Conclusions: We found that STAT3 mediated the formation of CRC stemness tumorspheres, and STAT3-downstram JUND as a prognostic marker using RNAseq with bioinformatics analysis.

Moreover, we discovered hsa-miR-4521 and miR30a-5p were mediated by STAT3 analyzed using small RNAseq, and the results suggested that ERRFI1 was a target of miR-30a-5p that was potential for maintaining cancer stemness.

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PRE-OPERATIVE ANTI-TNF THERAPY IN CROHN’S DISEASE IS ASSOCIATED WITH INCREASED COMPLICATIONS FOLLOWING ELECTIVE SURGERY Yang-Sheng Lin1,2,3, Ming-Jen Chen 2,3,4, Wei-Chen Lin2,3,4, Yuan-Hung Wang1,5, Chiehfeng Chen1,6 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan2 MacKay Medical College, New Taipei City, Taiwan3 MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan4 Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan5 Department of Public Health, School of Medicine, College of Medicine, and Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan6

克隆氏症術前抗 TNF 治療與選擇性手 術後併發症的增加有關 林揚笙1,2,3 陳銘仁2,3,4 林煒晟2,3,4 王淵宏1,5 陳杰峰1,6 臺北醫學大學臨床醫學研究所1 馬偕紀念醫院胃腸內科2 馬偕醫學院3 馬偕醫護管理專科學校4 衛生福利部雙和醫院醫學研究部5 臺北醫學大學公共衛生學科暨台灣考科藍研究中 心6 Background: Regarding the post-operative complications with anti-TNF agents preoperatively in Crohn’s disease (CD) are still debated. And the postoperative risk in CD patients following elective surgery might be different.

Aims: We aim to distinguish the associated risk of post-operative complications with preoperatively used anti-TNF agents in CD patients who underwent emergent or elective abdominal

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surgeries.

Methods: We performed a systematic review with meta-analysis from databases of MEDLINE, Embase, Cochrane Library, and Scopus. The enrolled CD patients who had preoperatively exposed anti-TNF agents 8 weeks to 12 weeks for abdominal surgeries. A subgroup analysis, according to the percentage of emergent surgery, was performed.

Results: The studies were classified into solely elective surgery (n=6), a low proportion of emergent surgery (n=6;＜20%), and a higher proportion of emergent surgery (n=1;＞75%).

The remaining studies were classified as nonreported (n=6). The results showed decreased heterogeneity in elective surgery (emergent surgery=0%) with post-operative infectious complications. The association between antiTNF agents and complications are significantly higher in CD patients who underwent an elective surgery (unadjusted OR, 1.80; 95% CI, 1.12–2.87; p=0.014) and in the non-reported group (unadjusted OR, 2.47; 95% CI, 1.40–4.37; p=0.002), but were insignificant in the emergent surgery groups.

Conclusions: There may be some increased risk of post-operative infection in patients exposed to anti-TNF agents before elective surgery.

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HEAT SHOCK PROTEIN 27 INFLUENCES THE INHIBITORY EFFECT OF CURCUMIN IN COLON CANCER CELLS Hung-Hua Liang, Yu-Jia Chang Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

熱休克蛋白 27 於薑黃素治療大腸癌細 胞扮演的角色 梁宏華 張育嘉 臺北醫學大學臨床醫學研究所 Background: Colorectal cancer (CRC) is high prevalence and death rate in Taiwan. Traditional treatments of CRC are surgical resection followed with adjuvant chemotherapy and/or radiotherapy.

Natural products have shown to be less toxic than synthetic compounds, and they have attracted much interest in recent research. Curcumin possesses antioxidant, anti-inflammation and is a promising anti-cancer agent.

Aims: We hypothesize that HSP27 levels may influence the cytotoxic effect of curcumin in CRC. Methods: We focus on the role of HSP27 in curcumin treatment of CRC. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting.

Results: It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in antiapoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen species, superoxide and

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autophagy induction levels in the HSP27-KD cells as compared to the control cells.

Conclusions: All these laboratory findings indicated that HSP27 can be a good predictive biomarker for curcumin resistance in CRC. With observation and modulation of the biomarkers, we can predict therapeutic efficacy and develop personalized therapy in the future.

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OUR EXPERIENCE OF EMERGENCY HERNIOPLASTY WITH LAPAROSCOPIC TEP OF AN INGUINAL INCARCERATED HERNIA, RETROSPECTED DATA ANALYZED IN TAICHUNG HOSPITAL, MINISTRY OF HEALTH AND WELFARE Chung-Hsiang Liu, Yu-Shyong Tong, Chin-Hung Tsai Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan

衛生福利部台中醫院回朔性資料分 析，腹膜外疝氣修補術於坎頓型鼠蹊 部疝氣運用之及經驗分享 劉中祥 唐于雄 蔡金宏 衛生福利部臺中醫院 Background: The definition of incarcerated hernia is If the contents of the hernia become trapped in the weak point in the abdominal wall, it can obstruct the bowel, leading to severe pain, nausea, vomiting, and the inability to have a bowel movement or pass gas. We provided an experience, laparoscopic TEP management of incarcerated hernia, a retrospective data reviewed and analyzed the difference between open and laparoscopic method hernioplasty in an incarcerated hernia, diagnosis in ED, which can’t be reduced initially. the emergency surgical intervention was planning with open or laparoscopic hernioplasty was design upon the hernia content could be reduced under anesthesia or not.

Aims: We provided an experience, laparoscopic TEP management of incarcerated hernia, a retrospective data reviewed and analyzed the difference between open and laparoscopic method hernioplasty in an incarcerated hernia.

Methods: We collected the data from 2012, January to 2018 December, a total of 41 patients, the total emergency hernioplasty is 41 cases, the 5 patients were not included (an incarcerated hernia could not be reduced and hemodynamically unstable status). male 31, female 5, mean age: 49.5 years old (from 3 to 96 years old), mean operative time is 87.509 minutes. The open hernioplasty is 31 cases, it was done when the patient either more than 70-yearold associated with other comorbidities and, or the hernia content could not be reduced under

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anesthesia even the young age. The laparoscopic hernioplasty is 10 cases; the 4 cases are TAPP, the 6 cases are TEP. the laparoscopic hernioplasty with TAPP was performed when the hernia content could not be reduced under anesthesia, the discomfort is less than 6 hours and there is no toxic sign was noted. The laparoscopic hernioplasty with TEP method was carried on when the hernia content could be reduced under anesthesia, the discomfort is less than 6 hours and there is no toxic sign was noted. All laparoscopic hernioplasty was performed in hernia content was reduced, tension free mesh repaired and an Fr.7 CW drainage tube was placed in the dependent site for drainage purpose. After TEP, then we checked the content is viable or not by a transperitoneal method. The mean operative time is no obvious differences between TAPP and TEP, mean operative time is 70. minutes in TAPP, 72 minutes in TEP. the postoperative followed up period is 2 years, including the postoperative wound pain, retractive discomfort, recurrent hernia the preoperative and postoperative pain score is recorded by VAS pain score (preoperative: VAS is 8-9, 1st postoperative day, the VAS in open method is 7-8 ,there are no obvious differences in laparoscopic hernioplasty with mesh repaired, VAS is 3-4 (VAS in TEP is 3-4, VAS in TAPP is 3-4), the hospital day; the open method was discharged in 7 days postoperative, the laparoscopic hernioplasty with mesh repaired was discharged in 4 days after procedure. the early return to daily activity was observed 2 months after the open hernioplasty, there’s one and half months after laparoscopic procedure who were went back to daily activity.

Results: The incarcerated type of inguinal hernia is an emergency condition and should be repaired with either open or laparoscopic method with or without mesh repaired immediately. In our experience and retrospected data analysis showed there’s no difference of postoperative satisfactory between the laparoscopic (TEP, TAPP) hernioplasty and open hernioplasty with mesh repaired in an incarcerated hernia, but the postoperative pain score and hospital day were short in the laparoscopic group.

Conclusions: The laparoscopic TEP hernia repair can be another choice in an incarcerated inguinal hernia. It could be performed safely and the recurrence rate is no difference compared to the open method.

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THE OCCURRENCE OF INTERVAL COLORECTAL CANCER: A TERTIARY HOSPITAL REPORT Shao-Ming Chiu, Lung-Sheng Lu, Wei-Chen Tai, Chih-Ming Liang, Shih-Cheng Yang, Cheng-Kun Wu, Chih-Chien Yao, Cheng-En Tsai, Seng-Kee Chuah, Yi-Chun Chiu, Keng-Liang Wu Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

間隔性大腸直腸癌之發生率及危險因 子：單一南部醫學中心之報告 邱紹銘 盧龍生 戴維震 梁志明 楊世正 吳鎮琨 姚志謙 蔡承恩 蔡成枝 邱逸群 吳耿良 高雄長庚紀念醫院胃腸肝膽科 Background: Colorectal cancer (CRC) remains the leading cause of death in Taiwan despite the efforts of CRC screening program. Early detection by regular surveillance are key points of prevention. But development of CRC between period of follow-up remains an unmet need that challenges the health and economic burden of Taiwanese.

Aims: To investigate the relationship of time to progression to interval CRC and identify the potential risk factors.

Methods: This is a retrospective chart review study which reviewed 464 CRC patients between 1st January to 31st December 2018 in our hospital and identify interval CRC among them. Interval colorectal cancer is defined as pathological diagnosed colorectal cancer within 5 years of last colonoscopy which was negative for malignancy.

Those patients with incomplete chart recording were excluded. We further analyze the potential risk factors relevant to interval CRC such as sex, age, underlying disease, previous pathologic type of polyps by univariate and multivariate analysis.

Results: A total of 15 patients were defined as interval CRC were identified in this study (3.23%, 5 males and 10 females, mean age: 69.4±7.34 (male) and 65.5±7.68 (female) years old). Ten patients were from the Proctologist division and five from the Gastroenterology

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department. The mean interval time of diagnosis were 1231.6±504.6 days in male patients and 809.2±609.8 days in female patients. Negative finding of polyp in last colonoscopy before diagnosis of colorectal cancer was found in 5 of these 15 interval CRC patients. Multivariate analysis showed that right side colon polyp demonstrated independent risk factors of interval colorectal cancer development in our observation.

Conclusions: The prevalence of interval CRC is 3.23%. Location of polyps over the right colon is relevant to the occurrence of interval CRC.

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PURELY LAPAROSCOPIC FEEDING JEJUNOSTOMY: A SINGLE SURGEON’S EXPERIENCE Ta-Chun Chou1, Ming-Chin Yu2,3, Chun-Nan Yeh2,3, Chao-Wei Lee2,3 Department of Surgery, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan1 Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Chang Gung University, Taoyuan, Taiwan3

腹腔鏡空腸造廔管：單一外科醫師的 經驗分享 周大鈞1 游明晉2,3 葉俊男2,3 李兆偉2,3 基隆長庚紀念醫院外科部1 林口長庚紀念醫院外科部2 長庚大學3 Background: For patients intolerable to per oral feeding such as advanced esophageal cancer, oropharyngeal cancer, or old cerebrovascular insult with recurrent aspiration pneumonia, feeding jejunostomy is indicated to maintain adequate enteral nutrition. Owing to advancement in laparoscopic surgery, we can now perform purely laparoscopic feeding jejunostomy with intracorporeal sutures. In the current study, we attempted to compare the outcome of laparoscopic feeding jejunostomy performed by a single surgeon with that of conventional open approach and describe our standard procedure of this approach.

Aims: we aimed to share our experiences on totally intracorporeal laparoscopic jejunostomy by a single surgeon compared to open method.

Methods: This retrospective study compared the variables including surgical indication, preoperative nutritional status, operation time, post-operative pain score, short-term and long-term post-operative outcome between conventional open and laparoscopic feeding jejunostomy between December 2012 and January 2019.

Results: A total of 30 patients who received laparoscopic feeding jejunostomy and 90 patients who underwent conventional open approach were included into the current study. All of the laparoscopic operations were performed by a single surgeon. Statistical analysis demonstrated

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that there were no significant differences in terms of surgical indication and postoperative outcome including bowel recovery, early or late postoperative complications between the two groups. The laparoscopic approach carries the inherent advantage of better postoperative cosmetics, lesser postoperative pain, and earlier postoperative ambulation.

Conclusions: Compared with conventional open surgery, laparoscopic feeding jejunostomy can be performed safely with comparable outcome.

Furthermore, it can provide young surgeons an opprtunity to excel laparoscopic technique and intracoporeal sutures. Further large scale prospective studies are warranted to validate our findings.

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DETECTION AND MANAGEMENT OF COLORECTAL SUPERFICIAL LESIONS ≦1.0 CM AS QUALITY INDICATORS OF COLONOSCOPY Meng-Yu Chen1, Yun-Liang Chang1, Hung-Chuen Chang1,2, Lee-Won Chong1,2, Yu-Hwa Liu1, Cheuk-Kay Sun1, Kou-Ching Yang1, Yu-Min Lin1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 School of Medicine, Fu Jen Catholic University, Taipei, Taiwan2

分析「大直腸瘜肉≦1.0 cm 篩檢及處 理方式」 ：大腸鏡品質評估 陳孟妤1 張允亮1 張鴻俊1,2 張麗文1,2 劉玉華1 孫灼基1 楊國卿1 林裕民1,2 新光吳火獅紀念醫院胃腸肝膽科1 輔仁大學醫學系2 Background: Identification of adenoma is important for the colorectal cancer (CRC) prevention.

Aims: We aimed to evaluate the detections and managements of small colorectal polyps to understand the quality of colonoscopy.

M e t h o d s : We r e t r o s p e c t i v e l y e v a l u a t e d individuals with colonoscopy in a single hospital between January 2015 and December 2018.

For cases with at least one small polyp (≦1.0 cm) detected by colonoscopy were enrolled for analysis. We reviewed the endoscopy reporting system and determined the quality of colonoscopy according to the metrics as follows: SADR (small adenoma detection rate): at least one small adenoma detected/ all colonoscopies.

SSDR (small SSA/P detection rate): at least one SSA/P detected/ all colonoscopies. PBR (polyp biopsy rate): small polyp removed by biopsy/ colonoscopies with small polyps. PPR (polyp polypectomy rate): small polyp removed by polypectomy/colonoscopies with small polyps.

CSR (cold-snaring rate): small polyp removed by cold snare polypectomy/colonoscopies with small polyps.

Results: A total of 24733 colonoscopies were done between January 2015 and December 2018. After 7769 cases were excluded due to

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nonstandard report, 16964 cases were enrolled for analysis. The colonoscopy numbers by year were 2338 (2015); 4395 (2016); 5240 (2017); and 4991 (2018). The SADR were 49.4%, 50.0%, 48.1% and 46.5% by year. The SSDR were 1.0%, 0.8%, 1.0% and 1.2% by year. The PBR were 35.2%, 35.4%, 34.3% and 30.2% by year.

The PPR were 66.4%, 68.7%, 72.2% and 77.8% by year. The CSR were 0.5%, 0.3%, 5.5% and 14.7% by year.

Conclusions: The SADR achieved the benchmark and the SSDR slightly increased by year, which suggest an adequate screening colonoscopy quality. A decreasing trend of PBR and an increasing trend of PPR and CSR were observed in small polyps management, which suggest the competent polypectomy is improving. Our results indicate that adequate adenoma detection rate does not guarantee a competent ability to remove the polyps, accordingly, development of novel metrics is necessary to determine the quality of polypectomy.

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CLINICAL AND PATHOLOGICAL FEATURES OF SUPERFICIAL COLORECTAL LESIONS WITH IIC COMPONENT IDENTIFIED BY COLONOSCOPY Yun-Liang Chang1, Guan-Hong Lai1, Chun-Yao Liao1, Hung-Chuen Chang1,2, Lee-Won Chong1,2, Yuh-Hwa Liu1, Cheuk-Kay Sun1, Kou-Ching Yang1, Yu-Min Lin1,2 Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 School of Medicine, Fu Jen Catholic University, Taipei, Taiwan2

大直腸凹陷型病灶之臨床與病理特性 分析 張允亮1 賴冠宏1 廖俊堯1 張鴻俊1,2 張麗文1,2 劉玉華1 孫灼基1 楊國卿1 林裕民1,2 新光吳火獅紀念醫院胃腸肝膽科1 輔仁大學醫學系2 Background: Identification of colorectal superficial depressed lesions are important because they usually carry more advanced features.

Aims: We aimed to evaluate the clinical and pathological pictures and the managements of colorectal superficial lesions with depressed component (IIc).

Methods: We retrospectively enrolled individuals with colonoscopy in a single hospital between January 2014 and December 2018. We identified colorectal superficial depressed lesion according to the colonoscopy reports. All the endoscopic photos of the superficial depressed lesions were subsequently reviewed by 2-3 experienced endoscopists to confirm the diagnosis on the basis of Paris classification. Age, gender, clinical, pathological pictures and managements of these IIc lesions were subsequently analyzed.

Results: A total of 66 superficial depressed lesions were identified among 31457 colonoscopies.

After reviewing process, 9 cases did not exhibit superficial IIc pictures and were excluded.

Remained 57 (0.18%) were enrolled for subsequent analysis. The mean age was 62 years old. Male gender was dominant (42 of 57; 74%).

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Their median diameter was 5.6mm. About 38.6% of these IIc-component tumors were located at proximal colon. The managements of these lesions included: biopsy (8.9%), polypectomy (40.4%), EMR (35.1%) and operation (5.8%).

Histological pictures of these depressed lesions revealed a significant proportion of malignant transformation, approaching to 18% (10 of 57). Among these 10 cancers with superficial IIc components, the proportion of submucosal invasion was as high as 70%.

Conclusions: The estimated prevalence of colorectal superficial depressed lesions was rare, but, have their specific tumor behaviors such as high proportions of proximal location, advanced histology and relatively deep invasion.

Managements of IIc lesions remained a critical challenge, accordingly, every endoscopist should have a better understanding of the presentations of IIc lesions.

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VEGETABLES AND FRUITS ARE COMMON AND IMPORTANT FOOD ALLERGENS IN TAIWAN Ying-Chi Wong1, Zhe-Ying Liu1,2, Chih Kang Huang1, Shih Kuan Li1,3, Tzee-Chung Wu1, Ching-Feng Huang1 Division of Pediatric Gastroenterology Nutrition, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Pediatrics, Taipei Municipal Wanfang Hospital, Taipei, Taiwan2 Department of Pediatrics, Yonghe Cardinal Tien Hospital, New Taipei City, Taiwan3

蔬菜與水果為台灣重要食物過敏原 黃映齊1 劉喆瑩1,2 黃治綱1 李士寬1,3 吳子聰1 黃清峯1 臺北榮民總醫院兒童醫學部兒童胃腸科1 臺北市立萬芳醫院小兒科2 天主教耕莘醫療財團法人永和耕莘醫院小兒科3 Background: Food allergy (FA) is a rising concern worldwide. Amongst the variety of foods in the common Asian diet, shellfish is a wellknown food allergen, while the role of fruits and vegetables on atopic diseases are usually underestimated.

Aims: To investigate the influence of fruits and vegetables on atopic diseases.

Methods: This is a nationwide, cross-sectional, randomized questionnaire survey conducted in 2012. Interviewee and their family members were enrolled. Atopic diseases including allergic rhinitis (AR), asthma, atopic dermatitis (AD) and urticaria were diagnosed according to the International Study of Asthma and Allergies in Childhood (ISAAC) criteria. The diagnosis of FA was established only if respondents reported doctordiagnosed FA. Results: Total of 9,160 questionnaires were enrolled. There were 415 respondents with fruit allergy (4.51%) and 270 were allergic to vegetables (2.94%). Shrimp and crab were the top two allergens in patients with AR, asthma, AD and urticaria. Fruits was the third leading allergen in these 4 atopic diseases (7.5%, 10.3%, 13.8% and 12.5%, respectively). Vegetables was the fourth commonly associated food allergen related with AR and urticaria (4.8% and 8.0%) and

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the fifth common association with asthma and AD (8.3% and 9.3%). In respondents with fruit allergy, 7.5% had AR, which was comparable to respondents whom reported allergy to vegetable, shrimp and crab allergy (4.8%, 15.4% and 9.9%, respectively). Similar to the condition of AR, interviewee reported close correlation of fruit, vegetable, or shellfish allergy to asthma, AD, and urticaria. Cases with shellfish allergy (total of 1,197) were related to 1.03±0.97 types of atopic diseases. Those with vegetable and fruit allergy had 1.17±0.84 and 1.16±0.86 kinds of atopic disorders, respectively. The association between vegetable and fruit allergy to atopic diseases including AR, asthma, AD, and urticaria demonstrates similarity to that of allergy to shellfish.

Conclusions: Fruits and vegetables are common and major allergens, no less than shellfish.

Compared to shellfish, both fruits and vegetables were associated with similar percentage and types of allergic diseases. Adequate evaluation and education regarding fruits and vegetables allergy should be provided to patients with atopic disorders.

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THE DIFFERENT TRANSITION MODES OF GUT DYSBIOSIS IN THE HOSPITALIZED PATIENTS DURING ANTIBIOTIC THERAPY Tien-Ching Lin1, Chiung-Yu Chen1, Jhen-Wei Ruan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan1 Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan2

接受抗生素治療之住院患者其腸道菌 相失調的不同變遷模式 林典慶1 陳炯瑜1 阮振維2 國立成功大學醫學院附設醫院內科部消化內科1 國立成功大學醫學檢驗生物技術學系2 Background: Many significant modulators interfere with human commensal gut microbiota in the hospitalized patients, especially antibiotic use. Furthermore, antibiotic-induced dysbiosis has been evaluated in the studies regarding the associated illnesses, such as Clostridium difficile infection; however, a prospective real-word cohort demonstrating the detailed mechanism of antibiotic-induced dysbiosis in Taiwan is lacking.

Aims: To evaluate the alternation of gut microbiota longitudinally in the hospitalized patients with two different modes of antibiotic exposure.

Methods: This was a prospective real-word cohort for proof of concept in a Taiwan tertiary medical center. We collected a series of fecal samples from the hospitalized patients with different modes of antibiotic exposure at the given time points. The collected stool specimens were processed and analyzed through nextgeneration sequencing for total (16S ribosomal DNA) and active (16S ribosomal RNA) microbiota. Afterwards, we compared the different components of the gut microbiota in each patient, and the therapy-related alternation with time.

Results: We enrolled four patients prospectively regarding two different modes of antibiotic exposure for investigating the effects on the homeostasis of gut microbiome; the two modes

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were either short-term (less than 10 days) or long-term (more than 12 days). (Table 1; Figure 1) There were two distinct patterns depicting the alternation of microbiota respectively, in both of which a major shift occurred more significantly at the level of species, rather than family or phylum. Under the short-term antibiotic exposure, the most representative gut microbes can be quickly restored within one to two weeks after antibiotic cessation. (Figure 2) In contrast, the long-term antibiotic exposure had altered the bacterial community gradually and finally the species richness dived abruptly; moreover, the microbial regrowth was relatively rapid after the adaptive species were selected out. (Figure 3) Notably, we found that the genera Bifidobacterium and Faecalibacterium played critical roles in the reconstitution of the homeostatic microbial intestinal ecosystem after antibiotic-induced dysbiosis.

Conclusions: The profound shits of original gut microbial species were not observed until a longer and vigorous antibiotic treatment course. Besides, the resilience of indigenous gut microbiome is significant than that in the previous reports and some allegedly beneficial microbes, such as Bifidobacterium, would survive better than other species. Moreover, the essential alternation of gut dysbiosis during or after antibiotic therapy seems to be different form that in the previous studies, and the advanced analytical techniques may contribute to this new observation. Our investigation could provide key elements for exploring dysbiosis associated disease and relevant therapy, such as fecal microbiota transplantation.

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HYBRID ENDOSCOPIC SUBMUCOSAL DISSECTION BY USING DISPOSABLE SNARE HAD HIGH R0 RESECTION RATE FOR RECTAL NEUROENDOCRINE TUMORS Wen-Hsin Hsu, Kai-Ting Ting, Dave (Chih-Wei) Huang Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

使用拋棄式內視鏡電刀圈實施混合型 內視鏡黏膜下剝離術對於直腸神經內 分泌腫瘤有極高的標本無殘留切除率 許文欣 丁楷庭 黃至偉 阮綜合醫院消化內科 Background: Previous literatures found that modified endoscopic mucoresecomy (M-EMR) for removal of rectal neuroendocrine tumor (NET) had good R0 resection rate and more reasonable cost and procedure time when comparing with endoscopic submucosal dissection (ESD).

Nevertheless, it inevitably needs to exchange to other scope or withdraw the scope for installation of devices such as band or cap. These devices often havelimit to single-user only and would be an extra medical expense. Hybrid ESD by using a disposable snare which is reimbursed by national health insurance system could perform resection of rectal NET at a single procedure. However, its complete resection rate is not yet clearly evaluated.

Aims: To study efficacy of hybrid ESD for NET at rectum.

Methods: The definition of hybrid ESD is in accordance with Japanese guideline for colorectal ESD. We used a 15 mm snare (ASM-1-S, COOK, Ireland) to perform all hybrid ESD. At first, circumferential mucosal incision was performed by snare tip. Different from precutting EMR, partial dissection at submucosal layer was necessary and was also done by using the snare tip. When the anchorage of the lesion was loosened and isolated well, it was snared tightly and deeply to ensure complete removal.

Results: From 2017/07 to 2019/05, a total of 11 rectal NET were resected by hybrid ESD,

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including two previous R1 resection lesions.

Male:Female=7:4 , Age=53.91±13.77 yrs , Size: 4.86 mm±2.03 mm. Tumor grade: G1=10; G2=1, En bloc resection rate: 100%. R0 resection: 10/11 (90.9%); The patient with pathologically R1 resection did not show any residual tumor at 3-months and 15-months colonoscopy followup. Two previous R1 resection lesion was also resected completely by hybrid ESD. Procedure time (if we excluded the two complicated cases)=318.1±79.8 seconds. Neither acute perforation nor delayed bleeding case was noted.

Conclusions: Hybrid ESD using a disposable snare had comparable high R0 resection rate with current recommended procedure. It was also effective as a salvage treatment. Owing to the efficacy, cost and procedure time, hybrid ESD by using snare tip should be considered first for rectal NET.

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BASELINE CHARACTERISTICS OF PATIENTS TREATED WITH VEDOLIZUMAB IN TAIWAN: REALWORLD EVIDENCE FROM TSIBD REGISTRY Wei-Chen Lin1, Chung-Hsin Chang2, Chia-Hung Tu3, I-Che Feng4, Jen-Wei Chou5, Chen-Shuan Chung6, Ming-Jium Shieh7, Hsu-Heng Yen8, Yuh-Hwa Liu9, Wei-Chen Tai10, Deng-Chyang Wu11, Wen-Hung Hsu11, Chien-Yu Lu11, Lung-Sheng Lu10, Tzung-Jiun Tsai12, Shu-Lun Tang13, Peng-Wen Pao13, Pei-Wen Lien13, Yizhou Ye14, Paul Dolin14, Shu-Chen Wei3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan3 Division of Gastroenterology and Hepatology, Chi Mei Medical Center, Tainan, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei city, Taiwan6 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan7 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan9 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan10 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan11 Division of Gastroenterology and Hepatology, 289

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Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan12 Medical Affairs, Takeda Pharmaceuticals Taiwan, Ltd.13 Epidemiology, Takeda Pharmaceutical Company Ltd.14

台灣接受 Vedolizumab 治療患者之基 本特質：台灣發炎性腸道疾病學會登 錄系統之真實世界實證 林煒晟1 張崇信2 凃佳宏3 馮意哲4 周仁偉5 鍾承軒6 謝銘鈞7 顏旭亨8 劉玉華9 戴維震10 吳登強11 許文鴻11 盧建宇11 盧龍生10 蔡騌圳12 唐述綸13 鮑鵬文13 連珮雯13 葉一舟14 Paul Dolin14 魏淑鉁3

台北馬偕紀念醫院胃腸肝膽科1 臺中榮民總醫院胃腸肝膽科2 國立臺灣大學醫學院附設醫院內科部3 台南奇美醫院胃腸肝膽科4 中國醫藥大學附設醫院胃腸肝膽科5 亞東紀念醫院肝膽胃腸科6 國立臺灣大學醫學院附設醫院腫瘤科7 彰化基督教醫院胃腸肝膽科8 新光吳火獅紀念醫院胃腸肝膽科9 高雄長庚紀念醫院胃腸肝膽科10 高雄醫學大學附設中和紀念醫院胃腸肝膽科11 高雄榮民總醫院胃腸肝膽科12 台灣武田藥品工業股份有限公司醫藥事務部13 Epidemiology, Takeda Pharmaceutical Company Ltd.14 Background: Vedolizumab (VDZ), the first gut-selective biological therapy approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) in adults, was made available in Taiwan in June 2017. The real-world characteristics of UC and CD patients receiving VDZ in Taiwan remain limited.

Aims: The study aimed to describe the baseline demographics and clinical characteristics of patients treated with VDZ for inflammatory bowel disease (IBD) in Taiwan.

Methods: Data on demographic and baseline characteristics were analyzed from the prospective registry of the Taiwan Society of IBD (TSIBD), in patients who had received ≥1 VDZ infusion. Descriptive statistics were reported.

Results: A total of 109 patients prescribed VDZ

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(UC: n=50 [45.9%]; CD: n=59 [54.1%]) were enrolled in the study between January 2018 and April 2019. Overall, 77 (70.6 %) were male and the average [standard deviation, SD] age at VDZ initiation was 42.0 [15.6] years (UC: 49.2 [15.0]; CD: 35.8 [13.3] years). The median (min-max) disease duration prior to VDZ initiation were 3.9 years (0.04-23.74) in UC and 3.1 years in CD (0.03-13.71). Overall, two-thirds (66.0%) of UC and 49.2% of CD patients were biologic-naïve.

The most common disease location at VDZ initiation in UC was pancolitis (60.4%) and in CD was ileocolonic segment (64.2%). Concerning disease behavior, the inflammatory type of CD was the most common (42.6%). Average (SD) baseline CD active index score was 251.7 (83.8) in CD and in UC, the average (SD) Mayo score was 8.8 (2.3). A total of 35.6% of CD and 6.0% of UC patients underwent prior bowel resection.

The median duration (min/max) from the most recent bowel resection to initiating VDZ were 4.5 (0.2/13.3) years in CD and 0.4 (0.2/8.0) years in UC. Conclusions: Over half of moderate to severe IBD patients initiating VDZ are biologic-naïve in Taiwan in real-world clinical practice, with a greater proportion observed in UC versus CD patients.

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COMPARISON OF DNA STABILIZERS AND STORAGE CONDITIONS ON PRESERVING FECAL MICROBIOTA PROFILES Yi-Ta Chan1,2, Chieh-Chang Chen1,2,3, Wei-Kai Wu4,5, Chih-Min Chang6,7, Suraphan Panyod2,6, Tzu-Pin Lu6,7, Jyh-Ming Liou1,2, Yu-Jen Fang2,8, Eric Y. Chuang6,7,9, Ming-Shiang Wu1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan2 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan3 Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan4 Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan5 Bioinformatics and Biostatistics Core Lab, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan6 Institute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taipei, Taiwan7 Department of Internal Medicine, National Taiwan University Hospital Yunlin branch, Yunlin, Taiwan8 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan9

比較不同 DNA 穩定器與糞便保存狀況 對於維持糞便微生物菌叢之研究 詹易達1,2 陳介章1,2,3 吳偉愷4,5 張智閔6,7 Suraphan Panyod2,6 盧子彬6,7 劉志銘1,2 方佑仁2,8 莊曜宇6,7,9 吳明賢1,2

國立臺灣大學生物資訊暨生物統計核心實驗室6 國立臺灣大學流行病學與預防醫學研究所7 台大醫院新竹分院內科部8 國立臺灣大學生醫電子與資訊學研究所9 Background: Appropriate storage of fecal sample is a critical step for the unbiased analysis of microbial communities in metagenomic studies.

Rapid freezing to – 80° C is usually considered to be the best-practice, but this approach is usually challenging. DNA stabilizing kits may provide a more convenient method to preserve and store clinical samples.

Aims: We evaluated the reliability of two collection kits (Stratec stool collection tube with stabilizer, #1038111200 and OMNIgene.GUT OMR-200) on preserving fecal microbiota.

Methods: Samples were collected from two locations of fecal specimen in four healthy volunteers. The samples were sub-aliquoted and stored in a – 80 ° C freezer, in Stratec and OMNIgene.GUT (incubation at ambient temperature for 0, 3, or 7 days). The fecal microbial composition was assessed by 16S rRNA amplicon sequencing.

Results: We found storage condition did not differ significantly in terms of alpha diversity. Samples stored in DNA stabilizers were still representative of original microbial community after 7 days at ambient temperature. The individual difference has the major contribution to the differences in microbial community composition, rather than storage conditions or sampling location. Sample subjected to stabilizers resulted in microbial community shift, compared with immediately frozen samples. A Linear discriminant analysis Effect Size (LEfSe) analysis revealed Faecalibacterium was significantly higher in samples stored in Stratec kits.

Conclusions: Our study reveals both Stratec and OMNIgene.GUT DNA stabilizers provide good microbiome preservation up to 7 days in the ambient temperature and would be a good alternative for fecal sample collection in large scale population-based studies.

台大醫院胃腸肝膽科1 台大醫院內科部2 國立臺灣大學醫學院臨床醫學研究所3 台大醫院北護分院內科部4 國立臺灣大學食品科技研究所5

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P.160

MESALAZINE MAY BE BENEFICIAL TO PHLEBOSCLEROTIC CASES WITH ACUTE SYMPTOMS Kyent-Yon Yie1, Chi-Su Sun2, Ming-Jen Hsu2, Hsing-Tao Kuo2, Chin-Yi Lin2, I-Che Feng2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Hospital, Chiali Branch, Tainan, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan2

Mesalazine 對於出現急性症狀之靜脈 硬化性大腸炎可能有助益 葉建榮1 孫啟書2 許銘仁2 郭行道2 林勤益2 馮意哲2 佳里奇美醫院胃腸肝膽科1 奇美醫學中心胃腸肝膽科2 Background: Phlebosclerotic colitis is a rare form of ischemic colitis involves the right hemicolon preferentially. It characterized by thread-like calcifications along affected colonic wall and mesenteric vein and colonoscopy showed dark-purple colored mucosa. This disease is non-thrombotic, non-inflammatory stenosis or occlusion of the mesenteric veins but the actual etiology and pathogenesis are not yet fully understood. The majority of cases occurred in patients with Asian background, mostly from Japan, Taiwan and China. Phlebosclerotic colitis may be complicated by colonic hemorrhage, perforation and death. Some reports have suggested that conservative management with bowel rest and hydration are beneficial in stable cases. However, surgery may be necessary when conservative management fails to improve hemorrhage, persistent abdominal pain or obstruction. There remained no effective medications for phlebosclerotic colitis with acute symptoms now. Mesalazine, also known as 5-aminosalicylic acid (5-ASA), is a medication used to treat inflammatory bowel disease.

Aims: The aims of this prelimitary study is to evaluate the effectiveness of mesalazine 2 g daily use (PENTASA ® Sachet, Prolonged Release Granules, 2 g) in case of Phlebosclerotic colitis with acute symptoms of abdominal pain, hemorrhage with or without obstruction.

Methods: Total 6 cases of acute Phlebosclerotic

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colitis with acute symptoms of right abdominal pain, colon hemorrhage with or without obstruction were enrolled. All these 6 patients had long term herbal medicine history. They all received colonoscopy with tissue proof and CT image to confirm the diagnosis. During the acute episode, the empiric antibiotics with adequate supportive treatment were administered since all these patients presented the ER. 3 cases treated with oral mesalazine 2 gm daily to 24 weeks and the other 3 cases without mesalazine treatment as control group.

Results: In the control group, all 3 cases received right colectomy within 4 weeks due to persistent abdominal pain with colon hemorrhage or symptoms of obstruction. All 3 cases with mesalazine treatment had stable conditions and relief of colon hemorrhage within 1 week and relief of right low abdominal pain gradually in the following weeks. The endoscopic follow-up revealed healing of deep ulcers in 20 weeks. No recurrent pain or hemorrhage or obstruciton noted til now.

Conclusions: This prelimitary pilot study suggests that melsalazine may paly role in case of phlebosclerotic colitis with acute symptomes.

However, further large-scale research is warranted to confirm the effectiveness.

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DIFFERENT RISK FACTORS FOR DELAYED POSTPOLYPECTOMY BLEEDING IN PATIENTS WITH A SINGLE POLYPECTOMY VERSUS MULTIPLE POLYPECTOMIES DURING A ONE-TIME COLONOSCOPY Chun-Wei Chen1, Wey-Ran Lin1, Chun-Jung Lin1, Ming-Yao Su1,2, Cheng-Tang Chiu1,2 Department of Gastroenterology Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

在一次性的大腸鏡檢中單次及多次瘜肉 切除後延遲性出血有不同的危險因子 陳俊瑋1 林蔚然1 林淳榮1 蘇銘堯1,2 邱正堂1,2 林口長庚紀念醫院胃腸肝膽科1 長庚大學醫學院2 Background: Colorectal cancer (CRC) is a common and lethal disease. Polypectomy can prevent the development of CRC. Although polypectomy is a safe procedure, there is still 1% bleeding rate after polypectomy. During screening colonoscopy, patients may have more than one colon polyp to remove in one-time colonoscopic procedure. However, data on the rate of delayed postpolypectomy bleeding (PPB) and risk factors for multiple polypectomies during a one-time colonoscopic procedure are limited.

Aims: The aim of the study was to evaluate the risk of delayed PPB of multiple polypectomies in a one-time colonoscopy.

Methods: From Jan 2015, to Jan, 2017, patients who underwent snare polypectomy in a referral center of northern Taiwan for polyp’s size between 6 and 20 millimeters (mm) were enrolled in this study. The PPB event was defined as the presentation of a bloody stool 14 days after the polypectomy and followed by repeat colonoscopic interventions. The demography of patients and the polyp characteristics, including the size, morphology and location, were recorded.

Descriptive statistics and frequency distributions were calculated. The data were analyzed by using either the Mann-Whitney U test for continuous

variables or chi-square test for categorical variables. Univariate and multivariate logistic regressions were used to examine the risk factors of delay PPB. Odds ratios (OR) and 95% confidence interval (CI) were calculated. Statistical significance was defined as p value＜0.05.

Results: A total of 1188 patients were enrolled in this study. 888 (74.8%) patients underwent a single polypectomy during one-time colonoscopy, and 300 (25.2%) patients underwent ≥ 2 polypectomies during a one-time colonoscopy.

There were 616 (69.4%) male patients in the single polypectomy group and 231 (77.0%) in the multiple polypectomies group. The median age in the single polypectomy group was 59 years (range: 19-96 years) and 61 years (range:20-96 years) in the multiple polypectomies group. The mean polyp size in both groups was 8 millimeters without statistically difference. The overall delay PPB was 1.1 %. Compared to the single polypectomy group, the bleeding rate in the multiple polypectomies group was significantly higher. (3.3% vs 0.3%; p=0.02) In the univariate regression analysis for bleeding risk factors, increases in the polyp size were significantly associated with delayed PPB in the single polypectomy group (OR: 1.3, 95% CI: 1.03-1.65, p=0.02). In the multiple polypectomies group, female was significantly associated with delayed PPB (OR: 3.7, 95% CI: 1.05-12.93, p=0.04) and a history of anti-platelet/coagulant agent use was a borderline factor for delayed PPB (OR: 4.85, 95% CI: 0.99-23.69, p=0.05). The patients’ age, polyp location, polyp morphology, polyp pathology, prophylactic hemoclipping, and the endoscopists’ experience were not found to be significant risk factors for delayed PPB in either group. By adjusting for sex, polyp size and history of anti-platelet/coagulant agent use in the multivariate regression analysis, polyp size was still an independent factor for delayed PPB in the single polypectomy group. (OR: 1.30, 95% CI: 1.021.65, p=0.03) Female and history of anti-platelet/ coagulant agent use were independent factors for delayed PPB in the multiple polypectomies group (OR: 4.07, 95% CI: 1.14-14.47, p=0.03; OR: 5.54, 95% CI: 1.09-27.94, p=0.03 respectively).

Conclusions: When performing ≥ 2 polypectomies during a one-time colonoscopic procedure, the rate of delayed PPB significantly increases. Polyp size was a risk factor for delayed PPB in single polypectomy. Female and history of anti-platelet/ coagulant agent use were risk factors for delayed PPB in multiple polypectomies.

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P.162

PROGNOSTIC VALUE OF SARCOPENIA IN PATIENTS WITH SYNCHRONOUS COLORECTAL LIVER METASTASES UNDERGOING HEPATIC RESECTION Chun-Hsien Chen1, Yueh-Wei Liu2, Chien-Chang Lu3, Chih-Chi Wang2, Ko-Chao Lee3, Hong Hwa Chen3, Wang-Hseng Hu3, Ching-Di Chang4, Chao-Hung Hung1,5 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan2 Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan3 Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan4 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan5

肌少症對大腸直腸癌同步肝轉移患者 接受肝切除的預後價值 陳俊憲1 劉約維2 盧建璋3 王植熙2 李克釗3 陳鴻華3 胡萬祥3 常景棣4 洪肇宏1,5 嘉義長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院肝移植中心2 高雄長庚紀念醫院大腸直腸外科3 高雄長庚紀念醫院放射科4 高雄長庚紀念醫院胃腸肝膽科系5 Background: The prognostic significance of sarcopenia has been widely studied in different cancer patients. This study aimed to analyze the influence of sarcopenia on overall survival (OS) in a homogeneous population of colorectal cancer

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patients with synchronous liver metastases undergoing hepatic resection.

Aims: NA Methods: A retrospective analysis of 119 patients who underwent hepatic resection for synchronous liver metastases was performed. Sarcopenia was determined using the Hounsfield unit average calculation (HUAC), a measure of psoas muscle size and density at preoperative abdominal CT scans. Sarcopenia was defined as an HUAC score of less than 22 HU calculated using receiver operating characteristic analysis. The prognostic relevance of clinical variables and OS was evaluated by the log-rank test and by multivariate Cox’s regression analysis.

Results: Patients with sarcopenia were older (p＜ 0.001) and had higher body mass index (p=0.028) and neutrophil-to-lymphocyte ratio (p=0.029) compared to those without sarcopenia. KaplanMeier curves showed that multinodularity (＞3) (p=0.005), tumor size (＞3 cm) (p=0.055), blood loss (＞300 cc) (p=0.027) significantly associated with the poor OS, whereas sarcopenia did not.

Multivariate Cox’s regression analysis showed that multinodularity (＞3) (hazard ratio (HR) 2.87; 95% confidence interval (CI), 1.50-5.47; p=0.001) and tumor size (＞3 cm) (HR 1.93; 95% CI, 1.05-3.57; p=0.035) were independent factors associated with OS. In a subgroup analysis, sarcopenia was a significant factor of poor OS in the patients with multinodularity (p=0.001).

Conclusions: Sarcopenia selectively impacts on OS among patients with multiple synchronous colorectal liver metastases after hepatic resection.

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THE CT FINDINGS OF DENGUE FEVER IN THE ABDOMEN Cheng-Yi Lin1, Pei-Ling Hsieh2 Department of Internal Medicine, Division of Hepato-Gastroenterology, Chi Mei Medical Center, Tainan, Taiwan1 Department of Medical Image, Chi Mei Medical Center, Tainan, Taiwan2

登革熱的腹部斷層掃描表現 林政頤1 謝佩玲2 奇美醫學中心胃腸肝膽科1 奇美醫學中心影像醫學部2 Background: There are few literature with descriptions about the imaging features of dengue fever. Sometimes the deferential diagnosis of dengue fever on CT may be neglected due to the main manifestations were similar to hepatitis.

Aims: To study and analyze the abdominal CT findings of dengue fever.

Methods: Analyze the abdomen CT image of patients who were diagnosed with dengue fever by serology retrospectively.

Results: There were six patient with dengue fever having positive finding on CT image. The main CT features of dengue fever in abdomen were periportal edema, pericholecystic effusion and ascites. Intraabdominal hematoma were also noted on CT study.

Conclusions: The main CT features of dengue fever in abdomen such as periportal edema, pericholecystic effusion and ascites shared the similar imaging features to hepatitis. However, combining with clinical manifestation and serology facilitate more accurate diagnosis of dengue fever.

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A HOSPITAL-BASED STUDY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN CENTRAL TAIWAN Hsiang-Chun Lai1, Chia-Hsi Chang2, Yu-Chuan Hsu2, Ken-Sheng Cheng2, Tsung-Wei Chen3, Jen-Wei Chou2 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2 Department of Pathology, China Medical University Hospital, Taichung, Taiwan3

中台灣一醫學中心的發炎性腸道疾病 病患之臨床研究 賴香君1 張家熙2 許鈺銓2 鄭庚申2 陳宗偉3 周仁偉2 中國醫藥大學附設醫院中醫部1 中國醫藥大學附設醫院消化系2 中國醫藥大學附設醫院病理部3 Background: Inflammatory bowel disease (IBD) is a chronic and relapsing disease of the gastrointestinal tract. The etiology of IBD remains unclear to date. The incidence and prevalence rates of IBD is still low in Taiwan comparing to Western reports.

Aims: The aim of this present study was to investigate the clinical characteristics of IBD patients in a medical center in central Taiwan.

Methods: From January 2000 to January 2019, we retrospectively reviewed patients diagnosed as IBD in our hospital. The diagnostic criteria were based on endoscopic, pathologic findings and peer review. Clinical characteristics including gender, age at diagnosis, alcohol/smoking habits, family history, extra-gastrointestinal tract manifestations, disease phenotype and behavior, colorectal cancer, avascular necrosis of hips, hepatitis B virus (HBV) infection, anti-neutrophil cytoplasmic antibodies (ANCAs), and treatment regimens were collected.

Results: One hundred and ninety patients with IBD were enrolled into our study. There were 80 patients with Crohn’s disease (CD) and 110 patients with ulcerative colitis (UC). We found out male predominance as 71% of all patients

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and the mean diagnostic age of all patients was 38.4 years (CD, 36.0 years; UC, 40.1 years).

The prevalence rates of ever-smoker/current smoker in CD and UC patients were 37.6% and 25.5%, respectively. Only 4.2% of all patients had a family history of IBD. The incidence rates of extra-intestinal manifestations/colorectal cancers/ avascular necrosis of hips were reported by 7.9%, 2.1%, and 3.2%, respectively. The seroprevalence of HBV infection in our study was 13.3%. In UC patients, the prevalence of perinuclear-ANCA (p-ANCA) was 22.2%. In disease phenotype and behavior of CD: L1, L2, L3 and L4 at diagnosis were 57.5%, 7.5%, 33.8%, and 1.3%, respectively; B1, B2, and B3 were 18.8%, 60.0%, and 21.3%, respectively. In disease extension of UC: E1, E2, and E3 at diagnosis were 18.2%, 42.7%, and 39.1%, respectively. In treatment regimens, we prescribed more aminosalicylate drugs in UC patients and more corticosteroids, immunomodulators and biological agents in CD patients. The cumulative bowel resection rate of all IBD patients was 18.4% and CD patients had significantly higher bowel resection rate than UC patients (38.8% vs. 3.6%).

Conclusions: In our present study, IBD patients showed male predominance, lack of familial clustering, lower rate of extra-intestinal manifestations/colorectal cancer/avascular necrosis of hips, and lower prevalence of p-ANCA in UC. In contrast, our IBD patients showed higher prevalence rates of HBV, avascular necrosis of hips and isolated ileal CD, and higher complications of CD at presentation.

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P.165

TREATMENT OF LATENT AND ACTIVE TUBERCULOSIS INFECTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE WITH BIOLOGICAL AGENTS: EXPERIENCE OF A MEDICAL CENTER IN CENTRAL TAIWAN Jen-Wei Chou1, Hsiang-Chun Lai2, Chia-Hsi Chang1, Ken-Sheng Cheng1, Hsing-Hung Cheng1, Tsung-Wei Chen3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan2 Department of Pathology, China Medical University Hospital, Taichung, Taiwan3

發炎性腸道疾病病患接受生物製劑治 療之潛伏性結核與活動性結核感染： 中台灣一醫學中心之經驗 周仁偉1 賴香君2 張家熙1 鄭庚申1 鄭幸弘1 陳宗偉3 中國醫藥大學附設醫院內科部消化系1 中國醫藥大學附設醫院中醫部2 中國醫藥大學附設醫院病理部3 Background: Inflammatory bowel disease (IBD) is a chronic and relapsing disease of the gastrointestinal tract. Comparing with Western countries, low prevalence of IBD and high prevalence of tuberculosis (TB) infection were reported in Taiwan. Biological agents have a great advance in treating patients with IBD, but they can increase the risk of TB infection Aims: The study was to investigate the incidence rate of latent TB and active TB infection in patients with IBD treating by biological agents.

Methods: From January 2000 to January 2019, we retrospectively collected IBD patients treating by biological agents at our hospital in central Taiwan. All patients underwent a QuantiFERONTB Gold (QFT) test to screen for TB infection before starting and during biological treatment course. The diagnostic age, gender, body mass index, types of IBD, comorbidities, laboratory data, type of biological agents, and results of QFT test were analyzed.

Results: One hundred and thirty IBD patients

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treated by biological agents were enrolled. There were 71 patients with Crohn’s disease (CD), and 59 patients with ulcerative colitis (UC). Male patients accounted for the majority in all IBD patients (75%). The mean age at diagnosis of all patients was 37.17 years and the mean age at starting biological therapy of all patients was 41.11 years. The ratio of usage in Adalimumab/ Vedolizumab/Infliximab/Golimumab were 95%, 8%, 5%, and 2% of all IBD patients, respectively.

The mean duration of follow-up was 31.2 months.

The results of QFT test were determinate in 120 cases (92%): ten were positive (8%) and 110 were negative (85%); and indeterminate in ten cases (8%). All patients with positive QFT test were diagnosed as latent TB and treated with prophylactic anti-TB therapy before the initiation of biological agents. The incidence of latent TB infection after biological treatment was 12% (CD, 15%; UC, 8%). Three patients (one CD patient and two UC patients) developed active pulmonary TB after biological therapy. The incidence rate of active TB infection after biologic therapy was 2.3% (CD, 1.4%; UC, 3.4%). All patient with active TB infection received the treatment of anti-TB agents.

Conclusions: Our present study demonstrates the incidence of latent TB is higher in Taiwan than in most Western countries and similar to other Asian countries. However, the incidence of active TB infection after receiving biological therapy is comparable to other Asian reports.

Thus, screening and monitoring of TB infection is needed and important for patients with IBD before starting and during biologic therapy in Taiwan.

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OUTCOME OF PATIENTS WITH COLORECTAL POLYPS THAT CONTAIN ADENOCARCINOMA Jiann Hwa Chen1,2, Wei-Chih Su1, Hung-Da Chen1, Chung-Hsien Li1, Lung-Yuan Hsu1,2, You-Chen Chao1,2 Buddhist Tzu Chi medical foundation, Taipei Tzu Chi Hospital, Taipei, Taiwan1 School of medicine, Tzu Chi University, Hualien, Taiwan2

局部癌化之大腸腺瘤病人的預後：單 家醫療機構十年的經驗 陳建華1,2 蘇偉志1 陳泓達1 李忠憲1 徐榮源1,2 趙有誠1,2 台北慈濟醫院1 慈濟大學醫學院2 Background: The timing of surgical resection in patients from whom polyps with invasive adenocarcinoma were excised has been questioned. Resection was recommended if the polypectomy margins were involved, if invasion extended into the stalk near the line of resection, or if the lesion was sessile and uncertainty existed regarding adequacy of excision.

Aims: To investigate if the sessile adenomatous polyps with focal invasive adenocarcinoma need colectomy.

Methods: This is a retrospective study from reviewing the medical records. A total of 4491 colonic polypectomies is performed in Tzu Chi hospital from June 2009 to May 2019. We classify the morphology of polyps as pedunculate and sessile type. There are total 24 patients to have invasive adenocarcinoma (T1) or adenocarcinoma in situ (AIS) from the endoscopically resected adenomatous polyps. Total Colonoscopy is performed at one- or two-years frequency for surveillance. These 24 patients were analyzed retrospectively, including short-term and long-term outcomes.

Results: Patients’ median age at diagnosis was 59 years (range 37–86 years). The follow up period is 18 to 138 months (median 65 months) Among these cases, there are 24 lesions (0.53%) revealing invasive adenocarcinoma (T1) or adenocarcinoma in situ (AIS), the former includes 10 patients and the latter consists of 14 cases.

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Two of the 10 T1 patients received surgery due that the endoscopic section margin is involved from cancer. Four patients have submucosal invasion. Half of the AIS patients (7/14) reveals sessile type polyps; however, 80% (2/10) of T1 patients showed sessile morphology. All patients, except one who loses follow up, survive disease free without any recurrence.

Conclusions: Surgical resection should be performed and certainly plays a pivotal role in the margin involved polyp, but the polyp with in situ or invasive adenocarcinoma may not be needed for colectomy if endoscopic excision is adequate.

P.167

THE OUTCOME OF STENTING AS A BRIDGE TO SURGERY FOR ACUTE OBSTRUCTIVE COLON CANCER: A SINGLE-CENTER EXPERIENCE Yu-Ting Huang 1, Kuo-Liang Wei1, Yi-Hsing Chen1, Wei-Ming Chen1,2, Kao-Chi Chang1, Cheng-Shyong Wu1 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

支架作為急性阻塞性大腸癌銜接手術 的效果：單一醫院經驗 黃宇庭1 魏國良1 陳奕行1 陳慰明1,2 張國基1 吳正雄1 嘉義長庚紀念醫院肝膽胃腸科1 長庚大學醫學院2 Background: The colostomy is considered the gold standard for emergent relief of malignant colonic obstruction, but stent placement is increasingly performed. This study aimed to share an experience about clinical outcomes for patients initially undergoing stent placement to prepare the afterward surgery.

Aims: To evaluate the efficacy, safety and clinical and oncological results of colonic stents in the initial therapeutic strategy of obstructive colon cancer.

Methods: In a single center. Descriptive and retrospective study (since 2010 December to 2019 June) in patients with clinical and radiological diagnosis of neoplastic obstruction of the colon in whom a colonic stent was indicated, analyzing the groups of stents as bridge to surgery (SBTS) and palliative stent. All cases were applied by non-covered stent and the lesions were from transverse colon to rectum.

Results: The study included 23 patients (10 female and 13 male) were evaluated. The mean age of the patients was 74 years old. For malignant colonic obstruction, the patients who underwent SBTS or palliative stent was 15 and 8, respectively. The site of colonic obstruction in the SBTS group was as follows: transverse colon=1 (6.67%), transverse/descending=1 (6.67%),

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descending colon=2 (13.33%), descending/ sigmoid=1 (6.67%), sigmoid=8 (53.33%), sigmoid/ rectum=1 (6.67%), rectum=1 (6.67%). The site of colonic obstruction in the palliative stent group was as follows: transverse colon=2 (25%), sigmoid=5 (62.5%), rectum=1 (25%). Technical success was achieved in all cases (23/23, 100%).

In the SBTS group, one case was with serosal involvement from surgical pathology specimens; the interval between stenting and the afterward operation was 48.3 days; the negative surgical margin of SBTS group was 93.3% (14/15) and the post-OP course was all smoothly. Besides, there were 2 patients did not receive operation as scheduled.

Conclusions: Initial treatment of neoplastic obstruction of the colon with a stent is an effective strategy in elective surgery and also avoids permanent colostomy in palliative patients.

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THE COMPARISON OF CLINICAL FEATURES OF COLONIC DIVERTICULITIS: DIFFERENCES BY LOCATION Si Hyeong Lee, Yun Jae Shin, Dong Hoon Lee, Tae Young Park, Soo Hyung Ryu, You Sun Kim, Jeong Seop Moon Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea Background: Colonic diverticulitis in Asian populations is observed predominantly in rightsided colon, while left sided-colonic diverticulitis is more frequently observed in Western populations.

There have been few studies comparing left and right-sided diverticulitis in Korea.

Aims: The purpose of this study was to evaluate the clinical features between right and left-sided colonic diverticulitis.

Methods: We retrospectively reviewed medical records of admitted patients who had been diagnosed with diverticulitis from January 2011 to October 2018 in Seoul Paik Hospital. The clinical data were evaluated based on abdomino-pelvic computed tomography (APCT), or colonoscopic findings.

Results: A total of 135 subjects (Male: Female=83 : 52, Age : 19~94 years old, Median age : 48 years old) were enrolled in the study. One hundred sixteen patients (85.9%) were in the right-sided colonic diverticulitis group and 19 patients (14.1%) were in the left-sided colonic diverticulitis group.

In the right-sided colonic diverticulitis group (male 70, 60.3%), the mean age was 45.8 (±11.8) years and it was significantly lower than left-sided colonic diverticulitis group (male 13, 68.4%, 63.2 (±16.7) years) (p<0.001). In addition, the hospital stay was significantly shorter in right-sided colonic diverticulitis group (6.3±3.2 days) comparing to left-sided colonic diverticulitis group (16.5±11.5 days) (p<0.05). There were no significant difference in Body mass index and blood test results (WBC, C-reactive protein, Hemoglobin, ESR) between right and left-sided colonic diverticulitis patients, however perforation (6.0% in right, 47.4% in left), was occurred significantly

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higher in left-sided colonic diverticulitis group (p-value < 0.001).

Conclusions: In Korea, colonic diverticulitis still occurs predominantly in the right-sided colon with mild clinical features. However, left-sided colonic diverticulitis showed more severe clinical features such as frequent perforation and prolonged hospital stay in aged patients.

P.169

NUCLEAR IMAGE TARGETING TO GZMB FOR MONITORING EXHAUSTION OF CD8+ T CELLS WITH LOSS OF ANTI-TUMOR ACTIVITY IN CIGARETTE SMOKERS AND TUMOR PATIENTS Chun-Chia Cheng1, Chung-Te Hsu2, Bi-Ling Yang2, Hsin-Chi Lin2, Cheng-Liang Peng3, Yi-Fang Chang4, Bin-Bin Shih2, Ai-Sheng Ho2, Chun Yeh2 Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan1 Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan2 Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan3 Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan4

靶向 CD8+ T 細胞 GZMB 蛋白進行核 醫造影監測抽菸者及癌病人 CD8+ T 細 胞的免疫活性與抗癌能力 程俊嘉1 許重得2 楊必玲2 林信吉2 彭正良3 張義芳4 施彬彬2 何愛生2 葉淳2 國家衛生研究院竹南分院分子與基因研究所1 振興醫院胃腸科2 核能研究所同位素組3 馬偕紀念醫院血液腫瘤科4 Background: Since the status of CD8+ T cells in patients with cancers play an important role for obtaining the immunotherapeutic success, and smoking has been demonstrated to affect the immunological activity.

Aims: This study aimed to investigate the molecular effect of smoking (nicotine) on exhaustion of CD8+ T cells in healthy volunteer and patient with cancers by targeted imaging to granzyme B (GZMB).

Methods: RNAseq and qPCR were utilized to search for the driver genes maintaining the activity of CD8 + T cells. Then the humanized tumor xenografts were used for validating the peripheral blood mononuclear cells (PBMCs)mediated anti-tumor effect through targeting to GZMB by nuclear imaging platform.

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Results: We found that CD8 T cells lost antiHCC827 cells in vitro in the healthy cigarette smokers. The RNAseq and qPCR data revealed that IL2RB and GZMB decreased in CD8+ T cells from a smoker, whereas IL2RB involved in IL2mediated signaling pathway to mediate GZMB expression. We validated that IL2RB and GZMB were diminished by nicotine treatment and in patients with cancers, including stomach cancer, hypopharynx cancer and lung cancer, resulting in decrease of PBMCs-mediated anti-tumor ability.

GZMB-targeted nuclear imaging revealed a lower radioactive signal in nicotine-treated PBMCs from a healthy volunteer and in patients with liver, thymus, and lung cancers.

Conclusions: This study demonstrated that low expression of IL2RB and GZMB caused by nicotine led to loss of anti-tumor effect in CD8+ T cells. Moreover, we validated that granzyme B-targeted radioactive agent was able to measure the cytotoxic activity of CD8+ T cells in a humanized tumor xenograft model, that may be applied for monitoring immunotherapeutic efficacy. +

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RISK FACTORS FOR GALLBLADDER STONES AMONG A HEALTH-CHECKUP POPULATION Cheng-Kun Liu1, Lan-Hsin Lu2, Yu-Te Wen2, Tzu-Yu Wang2, Ming-Hsun Wu2, Ming-Lun Han3 Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan1 Department of Laboratory Medicine, MinSheng General Hospital, Taoyuan, Taiwan2 Department of Integrated Diagnostics Therapeutics, National Taiwan University Hospital, Taipei, Taiwan3

健檢族群中膽結石相關危險因子之研 究 劉承昆1 呂藍欣2 温祐德2 王慈瑜2 吳明訓2 韓明倫3 敏盛綜合醫院內科部1 敏盛綜合醫院檢驗科2 臺大醫院綜合診療部3

Background: Cholelithiasis is a common disease and is associated with many conditions such as age, gender, obesity, dyslipidemia and diabetes.

However, the information about the prevalence and significant risk factors among a health-check up population is limited.

Aims: This study aimed to identify the risk factors of cholelithiasis among a health-checkup population in Taoyuan.

Methods: This study is a cross-sectional study.

We collected clinical data, abdominal ultrasound and laboratory biochemical reports from people who took a health check up in Min-Sheng General Hospital from 2015 to 2018. Logistic regression and stratified analysis were used to find the risk factors of cholelithiasis among a health-checkup population in Taoyuan.

Results: In this study, we totally collected 2,743 health-checkup participants and 170 subjects (mean age: 45.56 years) had cholelithiasis; the prevalence is 6.20%. With multivariable logistic regression analysis, age [odds ratios (OR): 1.308, 95% confidence interval (CI): 1.147-1.493], fasting blood glucose (OR: 1.009, 95% CI: 1.005-1.013), and HDL (OR: 0.983, 95% CI: 0.970-0.996) were significantly associated with cholelithiasis.

Stratified analysis with age showed, for the group of people＜50 years old, cholelithiasis was significantly associated with HDL (OR: 0.976,

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95% CI: 0.958-0.995); for the group of people ≧50 years old, cholelithiasis was significantly associated with BMI (odds ratios: 1.071, 95% CI: 1.011-1.133) and fasting blood glucose (OR: 1.013, 95% CI: 1.008-1.018). Stratified analysis with gender showed that the cholelithiasis was significantly associated with elder age (OR: 1.339, 95% CI: 1.115-1.609), waist circumference (OR: 1.029, 95% CI: 1.006-1.052) and fasting blood glucose (OR: 1.009, 95% CI: 1.004-1.014) in men.

In women, the cholelithiasis was associated with age (OR: 1.266, 95% CI: 1.048-1.529), fasting blood glucose (OR: 1.009, 95% CI: 1.001-1.016) and HDL (OR: 0.972, 95% CI: 0.953-0.993).

Conclusions: Based on the results of this study, we identified elder age, high BMI, high fasting blood glucose and low HDL as the important risk factors of cholelithiasis in a health-checkup population.

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TIMP-1 EXPRESSION IN BILE DUCT REGENERATION IN COMMON BILE DUCT LIGATION RATS Chi-Yi Peng1, Yii-Jim Yang2, Yii-Wen Hung3, Chiann-Yi Hsu3, Shu-Peng Ho1, Yen-Chun Peng4,5 Department of Veterinary Medicine, Taichung, Taiwan1 Division of neurosurgery, Center of Neuroscience Taichung Veteran General Hospital, Taichung, Taiwan2 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan3 Department of Internal Medicine, Chiayi Branch of Taichung veterans General Hospital, Chiayi, Taiwan4 Division of gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan5

金屬性蛋白酶之組織抑制因子在膽道 增生的表現探討 彭啟益1 楊怡津2 洪義文3 徐倩儀3 何素鵬1 彭彥鈞4,5 中興大學獸醫學系1 臺中榮民總醫院神經外科2 臺中榮民總醫院醫學研究部3 臺中榮民總醫院嘉義分院內科4 臺中榮民總醫院胃腸肝膽科5 Background: TIMP-1 has been identified as multifunctional molecule with divergent functions.

It participates in wound healing and regeneration, cell morphology and survival, tumor metastasis, angiogenesis, and inflammatory responses. An imbalance of MMP/TIMP regulation has been implicated in several inflammatory diseases.

In the process of liver fibrosis and bile duct regeneration, as a results of recurrent healing and regeneration, and thus TIMP-1 could be considered with an important role.

Aims: We aimed to determine the role of TIMP-1 in the CBDL mouse model.

Methods: Male Sprague-Dawley rats were divided into four groups: sham, sham plus amiodarone, CBDL, and CBDL plus amiodarone.

Amiodarone treatment was given in a daily dose of 10 mg/kg by body weight by means of intragastric gavage, beginning 5 days after CBDL.

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At 2 weeks after surgery, the animals in each group were sacrificed by introducing 100% carbon dioxide (CO2) gas in the euthanasia chamber at a flow rate of 20–30% chamber volume per minute.

Rat cytokine array were evaluated including TIMP-1 and other cytokines.

Results: Liver injury and fibrosis were exacerbated in CBDL rats with amiodarone. Both CBDL and amiodarone-treated CBDL rats showed bile duct regeneration. Mir-21 was significantly expressed in CBDL and amiodarone-treated CBDL rats. Amiodarone treatment augmented CBDL-induced TIMP-1.

Conclusions: CBDL alone resulted in greater overexpression of TIMP-1 compared with amiodarone alone. Amiodarone treatment augmented CBDL-induced TIMP-1.

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SAFETY OF ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION MORE THAN 15 MM ‒ A SINGLE MEDICAL CENTER EXPERIENCE FROM TAIWAN Chien-Yu Lin, Yao-Sheng Wang, Chien-Jui Huang, Ying-Jung Wu, Chiung-Yu Chen Division of Gastroenterology and Hepatobiliary, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

大於 15 mm 之內視鏡乳突大氣球擴張 術之安全性探討—台灣單一醫學中心 研究 林建佑 王堯生 黃千睿 吳瓔蓉 陳炯瑜 成功大學醫學院附設醫院內科部胃腸肝膽科 Background: Endoscopic papillary large balloon dilation is defined as balloon dilation larger than 12 mm, which is safe procedure comparing to traditional endoscopic sphincterotomy. However, safety of endoscopic papillary large balloon dilation more than 15 mm is still concerned from some experts for risks of bleeding, perforation or pancreatitis. Larger than 15 mm Endoscopic papillary large balloon dilation is still lacking much evidence.

Aims: To evaluate complications of equal to or more than 15 mm endoscopic papillary large balloon dilation comparing to less then 15 mm.

Methods: 231 patients from July 2013 to June 2018 underwent endoscopic papillary large balloon dilation (EPLBD) in our hospital were retrospectively analyzed. 13 patients were excluded due to unknown precise size of papillary balloon dilation, total 218 patients performed ERPLBD were enrolled finally. Patient backgrounds, indications, technique success rate, balloon dilation sizes, procedure complications were recorded. Balloon dilation catheter was used CRE from Boston Scientific Corporation.

Results: The mean age of patients was 73±15.4 y/o [11-105 y/o] with 96 men and 122 women (44%:56%). Indications of EPLBD were acute cholangitis (38.5%, n=82), choledocholithiasis (59.7%, n=138), biliary pancreatitis (0.9%, n=2), and bile duct dilation (0.9%, n=2). Technical

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successful rate for endoscopic papillary large balloon dilation was 100%. Balloon sizes were present as CRE 12-15 mm (60.6%, n=132), 1518 mm (28%, n=61), 18-20 mm (11.4%, n=25).

Balloon size＜15 mm were 39.4 % (n=86) compared to which size ≧ 15 mm as 60.6% (n=132). Complications of EPLBD between these different sizes showed 1.5% (n=2) v.s. 0.0% (n=0), p=1.0 in pancreatitis; 1.5% (n=2) v.s. 2.3% (n=2), p=0.5 in cholangitis, 3.0% (n=4) v.s. 2.3% (n=2), p=1 in bleeding, 0% (n=0) v.s. 1.2% (n=1) in perforation, 6.1% (n=8) v.s. 5.8% (n=5), p=1 in overall complications.

Conclusions: Endoscopic papillary large balloon dilation is safe procedure and acceptable complication rate no matter in different sizes. The upper limit of balloon size depending on diameter of upstream bile duct is still been followed. More cases still need to be enrolled in this series in the future.

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CLINICAL SIGNIFICANCE OF POSTENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) HYPERAMYLASEMIA Han-Jung Lin, Jian-Han Lai, Ming-Jen Chen, Cheng-Hsin Chu, Chih-Jen Chen, Ching-Chung Lin Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

內視鏡逆行性膽胰攝影術後高澱粉酶 血症之臨床意義 林瀚榮 賴建翰 陳銘仁 朱正心 陳志仁 林慶忠 馬偕紀念醫院胃腸肝膽科 Background: Post ERCP pancreatitis (PEP) was defined by abdominal pain with Amylase at least 3 times normal which had sometimes fetal complication. However, transient elevation in Amylase level without abdominal pain was known as post ERCP hyperamylasemia (PEH) which is frequently encountered in practice, but its clinical significance is unknown.

Aims: This study was to investigate the clinical significance between PEP and PEH by cannulation strategies, hospital stay, amylase level and Inhospital mortality.

Methods: From June 2016 to November 2017, the patients without acute or chronic pancreatitis before ERCP who was prevented PEP with rectal indomethacin in Mackay Memorial Hospital were enrolled retrospectively.

Results: A total of 162 patients were included. 9 patients (5.5%) were diagnosed with PEP, while 34 patients (20.1%) were diagnosed with PEH. Patients with PEP had higher percentage (more than 8 times) cannulations compared with PEH, but there is no significant difference (44.4% vs 26.5%, P=0.323). Amylase level in patients with PEP was higher than the PEH group (1934.6 vs 976.4 IU/ ml, p=0.000). Hospital stay in patients with PEP was also higher than PEH group (13.8 vs 7.4 days, p=0.083). There is no statistical difference of Inhospital mortality between patients with PEP and PEH (11.1% vs 2.9%, p=0.301).

Conclusions: Multiple cannulations might increase the incidence of PEP; the patients with PEH had shorter hospital stay and lower amylase level than the PEP group.

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THE EFFICACY AND ACCURACY OF ENDOSCOPIC ULTRASOUND (EUS) FOR DETECTING CBD STONES IN HIGH-RISK PATIENTS WITH NON-DIAGNOSTIC CT/MRCP Seng-Gaip Lem, Szu-Jen Wang, I-Hao Tseng, Meng-Shun Sun, Hsi-Jung Chen, Ching-Yang Tsai Divisionof Gastroenterology and Hepatology,Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

內視鏡超音波在診斷膽總管結石上的 準確性和優勢—與傳統影像 CT/MRCP 的比較 林成業 王嗣仁 曾逸豪 孫盟舜 陳錫榮 蔡青陽 阮綜合醫療社團法人阮綜合醫院消化內科 Background: Choledocholithiasis, or Common bile duct (CBD) stones are found in 10~15% of patients with symptomatic gallstone disease.

They may not cause symptoms for months or even years until they lodged in the duct and become obstructed, leading to severe complications such as cholangitis, pancreatitis, obstructive jaundice and sepsis, which might be fatal, if underdiagnosed or left untreated. In most circumstances, abdominal ultrasound (US) and computed tomography (CT) scan are the standard imaging studies used for detection of suspected CBD stones in patients presented with clinical features of abdominal pain, fever and jaundice. However, various studies showed that the sensitivity of abdominal ultrasound for detection of choledocholithiasis is as low as 26%, whereas the diagnostic rate of CT scan is only 56.5% in patients with CBD stones less than 5 mm. Nevertheless, MRI/MRCP has been widely used as a diagnostic tool in detecting CBD stones in the past decades, for its favorable sensitivity (85~92%) and specificity (93~97%) as compared to abdominal ultrasound and CT, in additionally, less invasive as compared to ERCP. However, the detection rate decreased to 33~71% in patients with small choledocholithiasis (＜6 mm). As such, we reported our experience with the diagnostic accuracy of Endoscopic Ultrasound (EUS) for detecting CBD stones in clinically suspicious patients, after non-diagnostic CT/MRCP.

Aims: In this study, we sought to assess the diagnostic performance of Endoscopic Ultrasound (EUS) for detecting CBD stones in high risk patients, after non-diagnostic CT/MRCP, with features of unexplained proximal CBD dilatation (＞6 mm).

Methods: This was a retrospective study, in which we reviewed 92 patients who received EUS studies in our institution during the period from January 2011 to May 2019, after nondiagnostic CT/MRCP with features of unexplained proximal CBD dilatation (＞6 mm), with or without jaundice. The patients in whom a diagnosis has been provided by prior imaging studies (CT/ MRCP/US), those with EUS diagnosis other than choledocholithiasis (such as CBD tumor or ampulla vater tumor), those with no further intervention (ERCP/surgery) or failure of ERCP after EUS diagnosis of CBD stones, and those who lost follow up after negative findings of EUS, were excluded from this study. The patients were selected as positive EUS results of CBD stones only if, stones could be seen endoscopically being extracted out of ampulla following the basket/ balloon sweep during ERCP procedure or, stones was successfully removed from bile duct during surgical choledocholithotomy. The patients with negative findings for CBD stones on EUS, were followed up with imaging studies (CT/MRCP/US) and liver functions tests for a period of 2 ~ 24 months.

Results: A total of 33 out of 92 patients was diagnosed with CBD stones on EUS, after nondiagnostic CT/MRCP, of which 30 patients underwent ERCP with stones withdrawal using basket/balloon sweep, and 3 patients received cholecystectomy + choledocholithotomy with stones removal, after failure of ERCP or patient choice. There were 2 cases with positive findings for CBD stones on EUS initially but ended up with negative findings on subsequent ERCP procedure. 57 patients with negative findings for CBD stones on EUS received regular follow-up with a period of 2 to 24 months, and showed no significant change in subsequent imaging studies (CT/MRCP/US) or biochemistry, additionally, remained clinically asymptomatic. In our study, EUS showed a high sensitivity (100%) and specificity (96.6%), for there were only 2 false positive cases, as well as impressive positive predictive value (94.3%) and negative predictive values (100%) for the detection of CBD stones.

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The positive likelihood ratio (LR+) was 29.5 and the negative likelihood ratio (LR-) was 0.

Conclusions: In our study, EUS has shown its superiority (sensitivity: 100%, positive predictive value: 94.3%) in the detection of common bile duct stones in high risk patients with nondiagnostic CT/MRCP. And patients with positive EUS findings (presence of CBD stones) should undergo endoscopic removal (ERCP) or surgical extraction (choledocholithotomy) of CBD stones, for the intention of relieving clinical symptoms (abd pain, jaundice) and preventing further complications (sepsis). Those with negative EUS findings do not need further invasive procedures (ERCP, surgery) but only close follow-up with US/CT/MRCP and biochemical tests, as in our study, the negative predictive value was 100%.

Further investigations will be indicated only if clinically symptomatic or disease progression.

Undoubtedly, MRCP/CT will be the first choice of examination scheduled for clinically suspected choledocholithiasis following abdominal ultrasound, because they were the least invasive among all. However, when CT/MRCP is negative, EUS is recommended to check for possible overlooking small CBD stones, before undergoing ERCP, a more invasive procedure which would lead to undesirable complications, such as pancreatitis (4%), cholangitis (1%), papillary bleeding (1%), perforation (0.5%).

EUS is a minimally invasive procedure with a procedural risk that identical to gastroendoscopy.

In our study, EUS has shown its efficacy and accuracy in examining and detecting common bile duct with small stones, bile sludge or even microlithiasis. Though, as a general rule, patient at high risk of choledocholithiasis are best treated by proceeding directly to endoscopic retrograde cholangiopancreatography (ERCP), for its concomittant diagnostic and therapeutic ability. For exception in whom prior attempts of unsuccessful ERCP, those at high risk of pancreatitis, those should be avoided of radiation exposure, elderly patients with severe comorbidities, pregnant women and those who might not tolerate such invasive procedure, EUS should therefore be considered as an alternative tool prior to ERCP, for its less invasive character and favorable diagnostic accuracy in detecting CBD stones or lesions.

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PRELIMINARY DATA OF CH-EUS (SONAZOID) IN CCH Yen-Chih Lin, Hsu-Heng Yen, Yu-Chun Hsu, Yang-Yuan Chen, Wei-Wen Su Changhua Christian Hospital, Changhua, Taiwan

彰基體系應用 Sonazoid 在 CH-EUS 上的經驗 林彥至 顏旭亨 徐友春 陳洋源 蘇維文 彰化基督教醫院 Background: “Sonazoid” (perflurobutane microbubbles), a second-generation contrast agent, was approved in Japan in 2007.Nowadays, this sonographic contrast agent was available in Taiwan since 2017. Our hospital has applied this agent to convex EUS study since 2018.6.

Aims: To evaluate the utility of new secondgeneration contrast agent”sonazoid” in convex EUS study.

Methods: From 2018.6 to 2019.6, total 27 patients received CH-EUS study using the contrast agent “sonazoid” (Olympus EU-ME2; GF-UCT260), We analysed our preliminary data and reviewed the related literature to improve our clinical technique.

Results: Within 27 patients who received CH-EUS with sonazoid, 23 patients have lesions located over pancreas, 2 patients have lesions over gallbladder, and the remaining 2 lesions are SEL and ampulla vater tumor. Among them. 4 patients received CH-EUS evaluation before or after EUSFNI for inoperable pNET. With the optimal setting of MI (mechanical index), we have proved that CHEUS is a very sensitive tool to distinguish mucin plug from intramural nodule in cases of IPMN. In addition, CH-EUS is useful to guide EUS-FNA, especially when obstructive pancreatitis is present in the background.

Conclusions: CH-EUS can improved the sensitivity and specificity of EUS, and improved the yeiling rate of EUS-FNA. In the future,this technique have potential to differentiate not only pancreatic disease, but biliary disease or SEL.

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COMPARISON OF DUODENAL MUCOSAL CHROMOGRANIN-A EXPRESSION IN NON-ALCOHOLIC FATTY PANCREAS DYSPEPTIC PATIENTS WITH AND WITHOUT ENDOSONOGRAPHY-DIAGNOSED EARLY CHRONIC PANCREATITIS: A CASE SERIES STUDY Chung-Tsui Huang, Tzong-Hsi Lee, Cheng-Kuan Lin Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei, Taiwan

在非酒精性脂肪胰與消化不良患者中 比較有無內視鏡超音波診斷早期慢性 胰臟炎之十二指腸黏膜嗜鉻細胞分泌 素 A 之表現：病例系列報告

group (N=11, pancreatic ARFI: 1.76±0.34 m/s), there were more endosonographic criteria score (2.45 vs 1.61, p=0.002), increased expression of chromogranin-A (p=0.001) and more severe fatty pancreas which defined by pancreatic duct blurring on abdominal sonography (91 % vs 46 %, p=0.062) as compared to non-PF group (N=13, pancreatic ARFI: 1.11±0.09 m/s). A total of 54 endosonographic abnormalities of ECP in these 24 patients showed: head (52%), body (31%) and tail (17%), a location pattern similar to pancreatic adenocarcinoma.

Conclusions: Pancreatic fibrosis and endosonography-diagnosed ECP could be surveyed in dyspeptic patients with NAFP and duodenal mucosa chromogranin-A could be a potential biomarker.

黃種粹 李宗熙 林政寬 亞東紀念醫院肝膽胃腸科 Background: Non-alcoholic fatty pancreas (NAFP) is hypothetically related to progressive fibro-inflammation of pancreas whose exocrine function controlled by enteroendocrine cell (EEC).

Early chronic pancreatitis is a new concept for defining initial stage of chronic pancreatitis with fibrosis. Theoretically, the expression of EEC would be different between fibrosis and nonfibrosis pancreas.

Aims: This study aimed to prove coexistence of NAFP and early chronic pancreatitis (ECP) using acoustic radiation force impulse (ARFI), endosonography and analysis of duodenal mucosa chromogranin-A, a surrogate for EEC. Methods: Dyspeptic patients were surveyed at digestive clinic and received abdominal echo, endosonography and serology tests.

Cases with organic causes of dyspepsia were excluded. Pancreatic fibrosis (PF) was defined as ARFI more or equal to 1.3 m/s. Early chronic pancreatitis was defined by at least 2 scores of Japan endosonographic criteria. Chromogranin-A of duodenal mucosa was analyzed by western blot.

Results: Between Jan and June 2018, 24 patients with NAFP were enrolled among 48 candidates and divided into two groups based on PF. In PF

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P.177

GALNT14 GENOTYPE PREDICTS POSTOPERATIVE OUTCOME OF PANCREATIC DUCTAL ADENOCARCINOMA Chun-Cheng Chiang1, Wey-Ran Lin1,2,3, Chau-Ting Yeh1,2,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Chang Gung University College of Medicine, Taoyuan, Taiwan3

GALNT14 基因型可預測胰臟管狀腺癌 術後的預後 江鈞誠1 林蔚然1,2,3 葉昭廷1,2,3 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院肝病研究中心2 長庚大學醫學系3 Background: Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with poor prognosis. The mainstay of the treatment is surgical resection followed by adjuvant chemotherapy. However, there is no reliable marker to predict the outcome. The single nucleotide polymorphism of N-acetylgalactosami nyltransferase14 (GALNT14) has been proven to predict the progression free survival (PFS), overall survival (OS) and response to chemotherapy in various types of gastrointestinal cancers, including hepatocellular carcinoma, cholangiocarcinoma, colorectal cancer, gastric cancer, and esophageal cancer. However, its role in PDA has not been studied.

Aims: This study aims to investigate whether GALNT14 genotype can be a prognostic marker for PDA. Furthermore, the association between GALNT14 and the clinicopathological parameters, and their predictive values will be evaluated.

Methods: One hundred and three PDA patients with surgical resection were enrolled for GALNT14 genotyping. The baseline characteristics data including age, gender, initial TNM stage, tumor markers, adjuvant chemotherapy and pathological parameters including resection free margin, tumor size, tumor location, tumor grading, peritoneal implantation, lymphovascular

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permeation, and perineural invasion were collected. For comparisons between groups, the Chi-square or Fisher’s exact tests were used for categorical data, and the twosample Student’s t-test or Mann-Whitney U test were used for continuous variables with or without normal distribution. Kaplan-Meier survival analysis with logrank test was used to compare outcomes.

Clinicopathological parameters were analyzed to identify the predictive factors for PFS and OS by univariate and multivariate analysis with Cox proportional hazards regression model. All the statistical analyses were performed with SPSS version 22.0 software (SPSS, Inc., Chicago, IL, USA).

Results: The genotype analysis of 103 PDA patients showed that 19.4%, 60.2% and 20.4% had GALNT14 “TT”, “TG” and “GG” genotypes, respectively. The patients with “GG” genotype had a mean OS time of 82.7 months (95% CI: 52.0-113.3) and “non-GG” genotype had 23.3 months (95% CI: 18.4-28.2). KaplanMeier analysis showed “GG” genotype had a significantly better OS compared to the “nonGG” genotype (p=0.005). However, there was no significant difference between “GG” and “nonGG” genotype in PFS (p=0.172). The baseline characteristics between patients with “GG” and “non-GG” types were compared, and no significant difference was found. Cox proportional hazard model demonstrated GALNT14 “GG” genotype, negative resection margin, and no initial tumor metastasis as independent predictors for favorable OS (p=0.004, p=0.016, p=0.018, respectively). The model also showed that patients underwent adjuvant chemotherapy was related to unfavorable PFS (p=0.042).

Conclusions: In conclusion, the GALNT14 “GG” genotype is associated with favorable OS in patients with resected PDA and could be considered as a prognostic marker.

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CLINICAL EXPERIENCES IN USAGE OF ENDOBILIARY RADIOFREQUENCY ABLATION FROM A MEDICAL CENTER IN TAIWAN Chien-Chih Tung1,2, Ming-Chu Chang2, Yu-Ting Chang2 Departments of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2

在台灣的一家醫學中心使用膽道內射 頻消融術的臨床經驗

and the rest one had the diagnosis of benign disease. All the patient tolerated the ablation successfully without immediate complication including perforation, bleeding or biliary tract infection. Lab data showed stationary hemogram before and after ablation. Only one case had temporarily elevating total bilirubin level, but it soon declined. Three cases had self-limited postprocedure pancreatitis.

Conclusions: Endobiliary radiofrequency ablation might be a promising technique to manage the biliopancreatic disease or disorder. It is easy to preform with acceptable complications. Further study with large number of patients is needed to obtain more useful information.

董建志1,2 章明珠2 張毓廷2 台大醫院綜合診療部1 台大醫院內科部2 Background: Plenty of etiologies may cause the obstruction of biliary tract, which may lead to biliary tract infection. The treatment choice is usually classified as curable surgery or palliative drainage. The palliative drainage included internal and external drainage. Recently, a developing technique of radiofrequency ablation in biliary tract has been reported. However, there is no related data in Taiwan.

Aims: To evaluate the feasibility and safety of a novel technique in management of biliopancreatic diseases by endobiliary radiofrequency ablation.

Methods: It was a retrospective study. Patients with the diagnoses of inoperable disease in biliopancreatic field including malignant and benign causes were enrolled. The procedure was performed by a skilled endoscopist under fluoroscopic guidance. An EndoHPB bipolar radiofrequency ablation catheter with two bare metal electrodes located separately on the tip was inserted through the scope to the lesion.

The energy level was set around 7~10W. Each session of ablation was about 90 seconds.

Blood sampling for hemogram, liver function and pancreatic enzymes were collected peri-ablation.

Results: Totally, 5 patients (male: 3, female: 2) were enrolled during the period from Non. 1, 2016 to Dec. 31, 2017. The median age of these patients is 63.2 years old. Four patients had the diagnoses of malignancy with advanced stage,

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FACTORS IMPACTING RECURRENCE OF CHOLEDOCHOLITHIASIS FOLLOWING ENDOSCOPIC BILE DUCT CLEARANCE Ta-Wei Wang, Shin-Yuan Chen, Chih-Sheng Hung, Ting-Chun Huang, Chi-Hwa Wu Cathay General Hospital, Taipei, Taiwan

內視鏡取石術後影響膽道結石復發的 相關因子探討與分析 王大維 陳世源 洪志聖 黃鼎鈞 吳啟華 國泰綜合醫院 Background: Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) is widely accepted as the modality of choice for the management of common bile duct stones.

One of late complications after endoscopic bile duct clearance is stone recurrence. However, recurrence rate of choledocholithiasis after endoscopic bile duct clearance vary widely among different studies, and no definite risk factors has been established.

Aims: To evaluate the rate of recurrence of choledocholithiasis and identify factors associated with the recurrence of bile duct stones in patient who underwent ERCP and EST with stone extraction.

Methods: All patients who underwent ERCP and EST for bile duct stone disease from January 2015 to December 2018 in the single tertiary hospital were enrolled. Statistical analysis was performed on patients with recurrence or who had undergone at least 6 months of reliable follow-up to detect the risk factors for recurrence.

Group differences in patient characteristics were evaluated using the Chi-square test except for the continuous variables which were tested using the Pair t test.

Results: A total of 38 patients (14.6%) developed recurrence of common bile duct stones after endoscopic bile duct clearance. Factors associated with recurrence were male (P=0.029), duodenal ulcers (P=0.015), larger angulation o f c o m m o n b i l e d u c t ( 1 4 3 . 3 5 ±1 3 . 11 v s 148.55±10.68, P=0.009) and receive prophylactic

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laparoscopic cholecystectomy (P=0.026).

Previous endoscopic bile duct clearance showed a trend towards significance (P=0.058). However, body mass index, previous cholecystectomy, diameter of common bile duct, periampullary diverticulum, bilirubin level, diabetes mellitus, hypertension and dyslipidemia didn’t influence the recurrence.

Conclusions: Bile duct stone recurrence is a possible late complication following endoscopic stone extraction and CBD clearance. It appears to be associated with male patient, duodenal ulcers, larger angulation of common bile duct and receive prophylactic laparoscopic cholecystectomy.

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P.180

URINARY TRYPSINOGEN-2 LEVEL AND LOCAL COMPLICATIONS OF ACUTE PANCREATITIS Hsing-Chien Wu1, Hsiu-Po Wang2,4, Chieh-Chang Chen2,4, Chien-Hsien Wu1, Ting-Hsu Liu1, Chih-Hsien Wang1, Ling-Na Shih3, Wei-Chih Liao2,4 Taipei Hospital, Ministry of Health and Welfare, Taipei, Taiwan1 Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan2 Lo-Sheng Sanatorium and Hospital, Ministry of Health and Welfare, Taiwan3 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4

predicting local complications [area under the ROC curve 0.65 (95% CI: 0.55-0.75) vs 0.48 (95% CI: 0.38-0.58), P=0.005]. At the optimal cutoff of 500 μg/L, the sensitivity, specificity, positive predictive value and negative predictive value of trypsinogen-2 level were 78.4%, 45.8%, 33.3%, and 86.0%, respectively. Urinary trypsinogen-2 level >500 μg/L was an independent predictor of local complications [adjusted odds ratio (OR), 3.72; 95% CI: 1.42-9.76; P=0.007]. By contrast, BISAP score ≥3 and pleural effusion predicted organ failure but not local complications.

Conclusions: In a prospective cohort, urinary trypsinogen-2 level >500 μg/L independently predicted local complications of AP.

Background: Local complications of acute pancreatitis (AP) carry risks of morbidity/mortality.

As trypsinogen is released into circulation and excreted from urine during AP, we hypothesize that urinary trypsinogen levels at the early stage of AP correlate with the degree of (peri)pancreatic autodigestion and better predict subsequent risk of local complications than predictors of the severity of AP. Aims: This study aimed to assess whether urinary trypsinogen-2 levels and Bedside Index for Severity in Acute Pancreatitis (BISAP) score on admission predicted subsequent local complications.

Methods: This prospective cohort study was conducted in a community hospital in Taipei, Taiwan. The study was approved by the ethics review committee (TH-IRB-0015-0013). From September 2015 to June 2017, consecutive patients who were admitted within seven days after the onset of AP and aged 20 or above were enrolled. The diagnosis of AP was made according to the revised Atlanta classification.

Patients with a history of stage 4 or stage 5 chronic kidney disease or nephrotic syndrome were excluded. All patients provided informed consent before participation in the study.

Results: Thirty-seven (25.7%) patients developed local complications. Urinary trypsinogen-2 levels were significantly higher in patients with local complications compared with those without local complications [median (interquartile range <IQR>), 3210 (620-9764.4) μg/L vs 627.3 (72.35895) μg/L, P=0.006]. Urinary trypsinogen-2 significantly outperformed BISAP score in

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P.181

PRIMARY ENDOSCOPIC CLOSURE FOR THE TREATMENT OF ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY RELATED PERFORATIONS: OUTCOME OF A SINGLE MEDICAL CENTER Hsing-Hung Cheng, Chun-Fu Ting, Cheng-Ju Yu, Chi-Ying Yang, Shih-Chieh Chuang, Wen-Hsin Huang Division of Hepatology and Gastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

內視鏡閉合術治療內視鏡逆行性膽胰 管攝影術導致的穿孔：一醫學中心的 經驗 鄭幸弘 丁俊夫 余承儒 楊其穎 莊世杰 黃文信 中國醫藥大學附設醫院內科部消化系 Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a routine procedure for the management of biliary and pancreatic diseases. Iatrogenic duodenal and pancreaticobiliary perforations associated with ERCP are rare but with a significant morbidity and mortality. The incidence of perforation after ERCP ranges from 0.09% to 1.67% and mortality up to 8%. Perforation of duodenal wall (Stapfer type I) usually requires surgical intervention because of high mortality rate. However, primary endoscopic closure has been recently described in selective cases.

Aims: The aim of this study is to analyze the clinical outcome of primary endoscopic closure for the patients with ERCP related perforations.

Methods: From Jan. 2015 to Jun. 2019, patients undergoing ERCP and suffering from ERCP related perforations were prospectively studied.

Primary endoscopic management was attempted while ERCP related perforations occurred, especially in Stapfer type I perforation.

Results: There were 17 (0.28%) perforations in 6130 ERCP during the past four and a half years.

Of all ERCP related perforations, 6 females and 11 males with mean age of 73.3 years (48 - 90), 12 (70.6%) Stapfer type I, 4 (23.5%) type II, and 1 (5.9%) type III perforations. No Stapfer type IV

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perforation occurred in this study. Of 12 type I perforations, 10 males and 2 females with mean age was 77.4 years (59 - 90), surgically altered anatomy (6 patients, 50%) was the most common etiology of perforation. Nine (75%) patients of type I perforation received primary endoscopic closure using hemoclip during ERCP with a success rate of 77.8%. Two (22.2%) of nine patients received surgical intervention due to failed endoscopic treatment. Difficult location for applying hemoclip is most important reason of failed endoscopic management. ALL Stapfer type II (4 patients) and type III (1 patient) perforations received nonoperative management.

Conclusions: Surgically altered anatomy is the most common etiology of Stapfer type I perforation. Primary endoscopic closure may provide a successful non-operative management in selective patients with Stapfer type I perforation.

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BILE DUCT STONES SIZE MAY INFLUENCE THE EFFICACY OF ENDOSCOPIC SPHINCTEROTOMY WITH OR WITHOUT LARGEBALLOON DILATATION FOR REMOVAL OF LARGE BILE DUCT STONES: A META-ANALYSIS Tang-Wei Chuang1, Joseph Leung2, Jyh-Jou Chen1, Pei-Lun Lee1, Hung-Da Tung1, Chun-Ta Cheng1, Hsu-Ju Kao1 Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan1 Division of Gastroenterology, UC Davis Medical Center and Sacramento VA Medical Center, Sacramento, California, USA2

膽管石頭大小影響乳突開口切開術合 併乳突氣球撐開術之臨床效度之統合 分析與比較 莊棠惟1 陳志州1 李佩倫1 董宏達1 鄭俊達1 高旭儒1 柳營奇美醫院胃腸肝膽科1 Division of Gastroenterology, UC Davis Medical Center and Sacramento VA Medical Center, Sacramento, California, USA2

stone clearance rate during the first session of the intervention and mechanical lithotripsy between ESBD and EST. Results: This meta-analysis compared the efficacy and safety of ESBD versus EST in removing＞10-mm stones. 16 studies (seven randomized control trials (RCTs); nine nonrandomized studies (non-RCTs)) were reviewed.

Patients were grouped according to stone size: Group A (＞17 mm), B (13-17 mm), and C (10-13 mm). In RCTs, ESBD has significantly better stone clearance rate during first session of intervention (OR=2.54, P=0.01, I2=54%) and requires less mechanical lithotripsy (ML) (OR=0.32, P＜0.010, I2=74%) compared to EST for stones＞10 mm. Subgroup analysis showed ESBD has significantly better initial stone clearance than EST in A (OR=2.30, P=0.02, I2=0%) and B (OR=4.14, P=0.0002, I2=21%) but no difference in C. ESBD required less ML than EST in B (OR=0.14, P＜0.0001, I2=53%) but no difference for A and C. Meta-analysis of the nonRCTs also supported the findings of the RCTs. Conclusions: ESBD had a significantly better initial larger stone (＞10 mm) clearance rate and required less ML than EST, especially for stones 13-17 mm. Stones＞17 mm limited the efficacy of ESBD.

Background: In recently year, endoscopic sphincterotomy (EST) along and combined with large balloon dilatation (ESBD) were commonly used for removal of large choledocholithiasis.

Endoscopic sphincterotomy with large balloon dilatation (ESBD or EPLBD) was first applied in 2003 by Ersoz et al which modified technique of EST and EPBD by introducing minimal to mild size of EST prior to using large-size balloon dilatation to dilated orifice of papilla. This modification allowed for larger CBD stones to pass through free from impaction.

Aims: The main purpose of the study was to compare the efficacy of ESBD and EST focus on retrieval larger common bile duct (CBD) stones.

Methods: A comprehensive searched from databases including PubMed, EMBASE, and WEB of SCIENCE that compared ESBD with EST for CBD stones over 10 mm removal were published between January 2003 to April 2018.

Meta-analysis with random-effects models were conducted to verify clinical efficacy including

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INCREASED RISK OF DEPRESSION IN PATIENTS WITH CHRONIC PANCREATITIS Tsung-Lang Lai1, Hsueh-Chou Lai2, Te-Chun Shen2,3, Chih-Yang Huang1 Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan1 Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2 Department of Internal Medicine, Chu Shang Show Chwan Hospital, Nantou, Taiwan3 Background: Although patients with chronic pancreatitis (CP) may be susceptible to the risk of development of depression, a largescale population-based study has not yet been performed.

Aims: The aim of this investigation was to compare the risk of developing depression between individuals with and without CP by conducting a population-based retrospective cohort study.

Methods: This study was conducted using data from the National Health Insurance Research Database of Taiwan (N=1,000,000). The case group included 1040 adult patients newly diagnosed with CP and recruited between 2000 and 2012. The control group consisted of 4160 participants from the general population without CP who were enrolled based on the propensity score for age, sex, and the comorbidities of hypertension, diabetes, hyperlipidemia, chronic pulmonary disease, chronic liver disease, and chronic kidney disease. The development of depression was evaluated till the end of 2013.

The relative risks of depression were estimated using the Cox proportional hazard model.

Results: The overall incidence of depression was found to be 2.66-fold greater in the CP group than in the non-CP group (15.8 versus 5.76 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.65 (95% confidence interval=2.06–3.42). Stratified analyses according to age, sex, and presence of comorbidity resulted in significant aHRs for depression associated with CP in all subgroups. Furthermore, patients with CP who visited the emergency room ≥2 times per

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year had a higher aHR of 2.67 (95% confidence interval=1.77–4.02) for developing depression than those who visited the emergency room <2 times per year.

Conclusions: A significantly higher risk of developing depression was detected in patients with CP than in the general population regardless of age, sex, and presence of comorbidity.

Moreover, patients with CP who frequently visited the emergency room had an increased risk of developing depression.

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Seongyul Ryu, Woo Chul Chung, Yeon-Ji Kim, Ik Hyun Cho, Jaeyoung Kim, Seonhoo Kim

Shunsuke Nakamura, Hiroyuki Kojima, Atushi Sofuni, Takayoshi Tsuchiya, Kentaro Ishii, Reina Tanaka, Ryosuke Tonozuka, Takao Itoi

THE EFFICACY OF ENDOSCOPIC ULTRASOUND (EUS) AFTER THE REMOVAL OF COMMON BILE DUCT STONE Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea Background: Although endoscopic retrograde cholangiopancreatography (ERCP) was a standard procedure for the removal of choledocholithiasis, the recurrence rate was quite high.

Aims: We aimed to investigate the prevalence and related factors of remnant biliary stone/sludge using endoscopic ultrasound (EUS) after the removal of common bile duct (CBD) stone and to evaluate the long term clinical outcomes.

Methods: Between June 2014 and June 2015, we prospectively designed and a consecutive series of patients who had ERCP for CBD stone were enrolled. After confirming that CBD stones had been completely eliminated by operator, EUS was performed to determine whether biliary stone/ sludge were remained. The patients had cholecystectomy, if gallstone was identified, and then was followed up with regular interval of 3 to 6 months. We investigated that symptomatic recurrence would happen.

Results: A total 130 patients were enrolled, and the rate of remnant biliary stone/ sludge after ERCP was 36.9% (48/130). The sole factor related to remnant biliary stone/ sludge was acute angulation of distal CBD (P<0.01). During the follow-up, overall recurrence rate was observed in 17.7% (23/130). Recurrent symptomatic choledocholithiasis was predicted by remnant biliary sludge and large diameter of CBD on multivariate analysis.

Conclusions: Acute angulation of distal CBD would have a possibility of remnant biliary stone/ sludge after ERCP. Remnant biliary sludge on EUS and large diameter of CBD would be strong predictors of symptomatic recurrence.

EUS evaluation after the removal of CBD stone could be an eďŹ&#x20AC;ective strategy in the treatment of choledocholithiasis.

A RARE CASE OF PANCREATIC LYMPHOEPITHELIAL CYST DIAGNOSED BY EUS-FNA

Tokyo Medical University, Tokyo, Japan Background: The LEC of the pancreas is a rare benign tumor that could be treated conservatively.

However, that diagnosis is sometimes difficult even using some imaging modality.

Aims: We report one case that EUS-FNA was a useful tool that can achieve a diagnosis without resection.

Methods: A 70-year-old male with a history of emphysema was introduced to our department for the further examination of a cystic lesion in the pancreas. The blood tests were within the normal range without a high level of CA 19-9.

Dynamic computed tomography showed a 35 mm multilocular cystic lesion with an enhanced septal wall in the pancreatic body. The pancreatic duct was not dilated and had no clear communication with the cystic lesion. Magnetic resonance imaging (MRI) showed that the cystic lesion had high intensity with a relatively low-intensity spot on T2 weighted image. That lesion showed a hot spot in that diffusion-weighted image of MRI. We suspected the intraductal papillary mucinous neoplasms with a mural nodule in the pancreas and performed endoscopic ultrasound examination (EUS).

Results: EUS showed the nodular-like part which was not enhanced by contrast-enhanced mode in the multilocular cystic lesion. From those examinations, pancreatic lymphoepithelial cyst (LEC) was suspected, but EUS guided ďŹ ne needle aspiration (EUS-FNA) was performed in order to rule out the possibility of malignancy. Pathological findings showed exudates with keratinization and cholesterol cleft. According to the results, we diagnosed with pancreatic LEC and decided to observe without surgery.

Conclusions: EUS-FNA might be one of option for diagnosing for LEC to avoid over surgery.

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COMBINED STENT-IN-STENT AND SIDE-BY-SIDE STENTING FOR HILAR MALIGNANT BILIARY OBSTRUCTION USING A NEW BRAIDED AND WEAVING STENT Sachiko Kanai*, Tomotaka Saito*, Hiroki Oyama, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Kazunaga Ishigaki, Kei Saito, Naminatsu Takahara, Tsuyoshi Hamada, Suguru Mizuno, Hirofumi Kogure, Yousuke Nakai, Kazuhiko Koike *Co-first authors Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Background: It is sometimes necessary to deploy multiple stents to manage hilar malignant biliary obstruction. During endoscopic bilateral placement of self-expandable metal stents (SEMSs), the side-by-side (SBS) method or partial stent-in-stent (SIS) method is useful. The SIS method is sometimes preferred given higher risk of adverse events associated with SBS. However, the SIS method can be more technically demanding owing to difficulties in passing a guidewire or stent delivery through the stent interstice.

Aims: Herein, we present a combined SIS and SBS technique using a novel SEMS that harbors braided and weaving construction thereby facilitating both SIS and SBS methods.

Methods: A 69-year-old woman with unresectable hilar cholangiocarcinoma was referred to our center, and endoscopic retrograde cholangiography revealed a Bismuth-Corlette classification IIIa stricture. After passing three guidewires to the bile duct at segment II (B2), VI (B6), and XIII (B8), an uncovered SEMS (Niti-S M Biliary Stent, 8-mmwide; Taewoong Medical Inc., Gimpo, Korea) was placed from B6 to the duodenum. Another SEMS (Niti-S M Biliary Stent) was placed from B8 to the duodenum in a partial SIS fashion. Subsequently, additional stent placement in B2 was attempted in a SIS fashion, but a guidewire could not be passed through the mesh walls of the overlapped SEMSs. Therefore, we decided to place the third SEMS in a SBS fashion over the guidewire placed in B2

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as a landmark. The delivery system was readily inserted to B2 without considerable interference with two SEMSs, and the third SEMS (Niti-S M Biliary Stent) was successfully deployed in a SBS fashion from B2 to the duodenum.

Results: No procedure-related adverse events were observed.

Conclusions: This newly-developed SEMS with braided and weaving construction allows both SIS and SBS methods. Combined SIS and SBS placement of the current SEMSs can increase the technical success rate of endoscopic stenting for hilar malignant biliary obstruction.

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VERY RARE LONG-TERM SURVIVORS OF PANCREATIC CANCER WITHOUT RESECTION: A CASE SERIES FROM YOKOHAMA Shihyao Cheng, Kensuke Kubota, Yusuke Kurita, Sho Hasegawa, Takamitsu Sato, Kunihiro Hosono, Atsushi Nakajima Gastroenteroloy and Hepatology, Yokohama City University, Graduate School of Medicine, Yokohama, Japan

given for three years showed complete response.

Recently, CA19-9 level was gradually increased, however, he has been working at his factory over ďŹ ve years and six months.

Conclusions: These findings suggested that the effective, unsurpassed and patients-friendly chemotherapy using S-1 and/or GEM for more than 3 years might contribute to the remarkable clinical courses.

Background: Although 5-year survival rate of pancreatic cancer (PC) was below 6%. Resection was the only therapy to ensure the long-term survival. Recent advances of chemotherapy could ameliorate the prognosis.

Aims: As PC survivors more than 5-year without resection was extremely rare, we experienced three long-term PC survivors, which would illustrate some treatment aspects.

Methods: All patients were histologically proven adenocarcinomas based on classification of Japanese Pancreas Society 2017. There were two unresectable PC patients and one T1 PC patient with surgery refusal. Chemotherapies and additional conservative treatments were given to all, such as insulin and/or pancreatic enzyme replacement therapy depend on the patientsâ&#x20AC;&#x2122; condition.

Results: All patients showed full performance status (PS) and received chemotherapy by weekly for more than three years. CA19-9 level was less than 100 U/mL in all patients. Case 1:77-year-old male was diagnosed as a locally unresectable T4 cancer in the pancreatic tail.

He was treated with five months S-1 due to thrombocytopenia, followed 7 years gemcitabine (GEM). He has been surviving for seven years and seven months. Case 2: 91-year-old male was detected as a locally advanced T4 cancer in the pancreatic tail. GEM was given by weekly more than three years, which showed stable disease.

He enjoyed his life three months before lung metastasis developed. He survived five years and six months. Case 3: 79-year-old male was regarded as T1 cancer with surgery refusal. S-1

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A RETROSPECTIVE ANALYSIS OF HEMOBILIA AFTER SELFEXPANDABLE METAL STENT PLACEMENT FOR MALIGNANT BILIARY OBSTRUCTION Tomotaka Saito1, Yousuke Nakai1, Hiroyuki Isayama1,2, Tsuyoshi Hamada1, Suguru Mizuno1, Sachiko Kanai1, Hiroki Oyama1, Tatsunori Suzuki1, Tomoka Nakamura1, Tatsuya Sato1, Kazunaga Ishigaki1, Ryunosuke Hakuta1, Kei Saito1, Naminatsu Takahara1, Hirofumi Kogure1, Minoru Tada1, Kazuhiko Koike1 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan1 Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan2 Background: Endoscopic placement of selfexpandable metallic stent (SEMS) is established as palliation for malignant biliary obstruction (MBO). Hemobilia is a rare but can be a lifethreatening complication after SEMS placement.

Aims: The aim of this study was to explore risk factors for this rare complications and to analyze treatment outcomes such as transcatheter arterial embolization (TAE) or compression by covered SEMS. Methods: This is a single center, retrospective analysis of 683 patients who underwent SEMS placement between June 1992 and April 2018.

Hemobilia is defined as hemorrhage from the papilla conďŹ rmed by endoscopy, extravasation of contrast media or pseudoaneurysm on contrastenhanced computed tomography (CT). A Cox hazard regression analysis was performed to explore risk factors of hemobilia.

Results: Hemobilia developed after SEMS placement in 25 cases (3.7%). Patient characteristics of 25 cases with hemobilia and 658 cases without hemobilia are shown in Table.

The risk factor analyses reveled the use of antithrombotic agents (hazard ratio [HR], 4.03; P <0.01) tumor invasion to the adjacent vessels (HR, 3.15; P <0.01) and multiple uncovered SEMS (HR, 2.48; P=0.03). As the initial treatment,

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TAE was performed in 6 cases, which was successful in all cases. Covered SEMS insertion was performed in 6 and achieved hemostasis in 3. Among 3 cases with unsuccessful hemostasis, 2 cases underwent additional TAE, and the other one died. The remaning13 cases were managed conservatively at first, but 2 cases needed TAE. After all, hemostasis was accomplished in 24 cases (96%).

Conclusions: TAE was effective when CT revealed pseudoaneurysm or extravasation. The role of covered SEMS placement was limited as a treatment for hemobilia.