2020消化系聯合學術演講年會摘要手冊

2020 消化系聯合學術演講年會 會長演講 ............................................................................................... 1 特別演講 ............................................................................................... 3 外賓演講 ( 一 ) Clinical Outcomes in Patients Treated with Nucleos(t)ide Analogues for Chronic Hepatitis B............................................................................ 5 ( 二 ) To Eliminate HCV Infection in Japan ...................................................... 8

兩性課程 ............................................................................................... 9 WHO 消化管病理分類 - 臨床與病理的對話 ......................................... 10 專題討論 ( 一 ) Application of Artificial Intelligence in Gastrointestinal Diseases.......... 12 ( 二 ) HCV Elimination in Community ............................................................ 17 ( 三 ) Fecal Microbiota Transplantation (FMT) of the Current Situation and the Future ...................................................................................... 21 ( 四 ) Current Application of Human Tissue and Pluripotent Stem Cell in GITract-Possibility and Challenge ........................................................ 25 ( 五 ) Recent Advances and Future Challenges of IO in GI Cancers ............ 30 ( 六 ) Challenges in the Management of GERD in 2020 ............................... 32 ( 七 ) Unmet Needs of Current Chronic Hepatitis B Treatment in Taiwan ..... 35 ( 八 ) Factors Predicting Outcome in IBD ...................................................... 38 ( 九 ) Update of Pancreatobiliary Endoscopy ................................................ 42 ( 十 ) Pancreatic Cancer Progression: Novel Molecular Mechanisms and Translational Opportunities ................................................................... 48

一般演講 C 型肝炎（一） ............................................................................................. 52 B 型肝炎（一） ............................................................................................. 57 B 型肝炎（二） ............................................................................................. 61 肝腫瘤（一） ................................................................................................ 65 肝硬化及其他肝病 ......................................................................................... 70 脂肪肝相關疾病 ............................................................................................. 74 上消化道疾病（一）...................................................................................... 78 下消化道疾病 ................................................................................................ 82 膽胰疾病（一） ............................................................................................. 87 其他消化道疾病 ............................................................................................. 91 C 型肝炎（二） ............................................................................................. 95 肝腫瘤（二） ................................................................................................ 98 上消化道疾病（二）.................................................................................... 102 膽胰疾病（二） ........................................................................................... 106

壁報展示 肝 .................................................................................................................110 消化道及膽胰疾病 ....................................................................................... 178

2020 消化系聯合學術演講年會

論文摘要

台灣消化系醫學會 ( 第五十屆 ) 學術演講年會 台灣消化系內視鏡醫學會 ( 第二十九次 ) 學術演講年會

2020 消化系聯合學術演講年會

會長演講（台灣消化系醫學會） DIAGNOSTIC GASTROINTESTINAL ENDOSCOPY AND PATIENT SAFETY Gi-Shih Lien（連吉時） 臺北市立萬芳醫院

Endoscopy is the most advanced and available tool for diagnosing the gastrointestinal (GI) lesions, although it is an invasive procedure. Dr. Kussmaul invented rigid type gastroscope in 1868, and since then diagnostic endoscopy has dramatically progressed through the stages of Dr. Rudolf Schindler’s semiflexible gastroscope and Dr. Hirschowitz’ as well as Japanese flexible fiberscopes. Along with the development of electronic endoscope in 1984, diagnostic and therapeutic endoscopy for early GI carcinoma has also evolved smoothly into more advanced techniques. However, we need a disruptive innovation of endoscope to minimize preventable harms of the invasive procedures to secure patient safety.

Early diagnosis of small intestinal lesion by endoscopy was so difficult until year 2000, when an Israeli company Given Imaging Ltd. introduced the innovative capsule endoscope (CE). Although CE came into the spotlight since its debut, there still are many basical limitations, which need more input of research and development to improve battery life, illumination, optics, angle of view and locomotion. At present, more researchers put their foci on locomotion of CE in GI tract by magnetic fields, including three axes Helmholtz coils and robot assisted magnetic steering; our NTU/WFH Maglev project has also developed a magnetic steering CE system with a convenient NdFeB alloy handset, named magnetic

field navigator (MFN). The MFN may make yaw, pitch and roll along three principle axes of the CE, in addition to pulling and turning around. We use the MFN to navigate the wired CE in the upper GI endoscopy, especially to facilitate locomotion in the capacious stomach. Artificial intelligence (AI) is proposed in the modern approach to machine learning and deep learning. To follow this trend, we developed an AI and mechanically assisted capsule colonoscope, which evolved from the original wired CE and MFN. In vitro and in vivo studies demonstrated the feasibility of an automatic model of colonoscopy in the future.

The first generation observation CE is propelled passively by GI tract peristalsis; a series of relevant research and development makes the second generation locomotive CE actively steered by magnetic fields, which may be AI and mechanically assisted. In 2008, Valdestri et al. succeeded in deploying a clip in vivo by a wireless magnetically steered clipping capsule, this first therapeutic capsule might start a new era of third generation CE with potential of treating GI lesions. Albert Einstein had mentioned: Without some sort of bold and wild guess, is generally impossible to have the progress of knowledge. The disruptive innovation of single use CE may provide sterile, reliable and convenient modalities of endoscopy, in which conscious sedation is not necessary.

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2020 消化系聯合學術演講年會

會長演講（台灣消化系內視鏡醫學會） CHALLENGE OF EARLY GASTRIC CANCER: FROM DIAGNOSIS TO TREATMENT Chun-Chao Chang（張君照） 臺北醫學大學附設醫院

Gastric cancer (GA) is the fifth leading cause of cancer death worldwide. It is also the eighth common cancer and seventh cancer mortality in Taiwan. Screening can effectively reduce GA mortality in high prevalent areas, but the optimal screening strategies are still in debate. Diagnosis of tumor in early stage, i.e., early gastric cancer (EGC), is essential for reducing cancer death by curative treatment. The endoscopists should have abilities to identify high-risk preneoplastic conditions (atrophy, intestinal metaplasia), distinguish neoplastic lesions from non-neoplastic lesions, and determine tumor extent and depth. Apart from white-light imaging, endoscopists should be familiar with image-enhanced endoscopy, e.g., magnifying narrow-band imaging,

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for an accurate diagnosis before management.

Endoscopic resection (ER) especially endoscopic submucosal dissection (ESD) has become a standard local treatment for some patients with EGC who lack lymph node metastasis. The criteria for ER had been developed in Japan with excellent clinical outcomes.

There are still controversies in the ESD expanded indication. Additionally, some blurry conditions for ESD including undifferentiated or mixed-type EGC need further clarification. The curability and most suitable management after non-curative resection also need further evaluation. All endoscopists must make effort to face the challenge of EGC, from diagnosis to treatment, via reducing impact of GA to promote mankind health and decrease socioeconomic burden.

2020 消化系聯合學術演講年會

特別演講 FINITE NUCLEOS(T)IDE ANALOGUE THERAPY IN HBEAG- NEGATIVE CHRONIC HEPATITIS: OUTCOMES AND MANAGEMENT Yun-Fan Liaw（廖運範） 中央研究院、長庚大學醫學院

Potent nucleos(t)ide analogues (NUC), such as entecavir and tenofovir disoproxil fumarate, are able to suppress HBV DNA to undetectable level. These agents have no direct action on cccDNA, a very stable template for HBV production, hence long-term or even life-long NUC therapy is required in HBeAgnegative patients to maintain HBV suppression and to achieve the ultimate therapeutic goal of HBsAg loss.

However, there are foreseeable concerns of indefinite long-term or life-long NUC therapy, including issues of drug resistance, financial burden, willingness/ adherence and loss-to-follow-up during indefinite long term NUC therapy. Without off-therapy monitoring, patients who lost to follow-up have high risk of severe hepatitis flare leading to hepatic decompensation/ hepatic failure. Studies have shown that cessation of NUC therapy in HBeAg-negative patients with maintained HBV suppression >1-3 years is feasible and reasonably safe. More recent cohort studies and a randomized controlled trial have further shown greatly increased HBsAg loss rate after stopping NUC therapy. With these, a paradigm shift from indefinite/ life long to finite NUC therapy in HBeAg-negative patients with chronic hepatitis B is emerging. The outcomes and management of this strategy need to be addressed.

Within 1 year after stopping NUC, ~80% of the patients may encounter virologic relapse (HBV DNA >2,000 IU/mL), which may coincide with or be followed by clinical relapse (ALT >2X ULN) in ~60% or hepatitis flare (ALT >5X ULN) in ~50% of the patients. The incidences are higher after stopping TDF

than ETV. As the results of robust immune response upon reexposure to large amount of HBV, hepatitis flare may resolve spontaneously if the host response is dominating over HBV (host-dominating flare) or end up with persistent/intermittent hepatitis activity or deterioration to hepatic decompensatin if HBV is dominating over the host response (virus-dominating flare). Our large study involving 691 patients showed low incidence of hepatic decompensation, with a 5-year cumulative incidence of 0% in 383 patients with CHB and 2.95% in 308 patients with cirrhosis, during a median follow-up of 3 years after EOT. Notably, off-NUC hepatitis flares after cessation of TDF occur much earlier (median 12 vs 33 weeks; P <0.001) and are more severe than those after ETV. Importantly, “no retreatment” is a strong predictor of HBsAg loss.

Hence it is crucial to make right retreatment decision that is not too soon to allow sufficient immune clearance facilitating further HBsAg decline towards HBsAg loss and also not too late to prevent adverse outcomes. Therefore, proper monitoring, assessment and retreatment decision are critical in the strategy of finite NUC therapy. Clearly, patients with impending or overt hepatic decompensation require immediate retreatment. In principle, patients with persistent clinical relapse >3 months also require retreatment.

For patients with hepatitis flare with normal bilirubin and INR, decision based on current biochemical marker(s) is safe but may be too soon in those whose hepatitis flare may resolve spontaneously. Combined HBsAg/ALT kinetics during hepatitis flare may help differentiation between types of hepatitis flare for

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2020 消化系聯合學術演講年會

retreatment decision that is not too late for patients with “virus-dominating flare” and not too soon or even not necessary for patients with “host-dominating flare”. As for the longer-term outcomes, studies have shown that the incidence of hepatic decompensation and HCC are not higher after interruption of NUC

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therapy as compared with those continued therapy.

In conclusion, the strategy of finite NUC therapy in HBV suppressed HBeAg-negative patients is feasible and safe if proper off-therapy monitoring and timely retreatment are provided.

2020 消化系聯合學術演講年會

外賓演講（一） CLINICAL OUTCOMES IN PATIENTS TREATED WITH NUCLEOS(T)IDE ANALOGUES FOR CHRONIC HEPATITIS B Young-Suk Lim Department of Gastroenterology, Liver Center, Asan Medical Center, Seoul, Korea

Introduction Although the universal hepatitis B virus (HBV) vaccination program has been successfully implemented for almost three decades in Korea and many Asian countries, most liver disease- and liver cancer-related deaths occur in unvaccinated middleaged and elderly adults. Therefore, considering the birth cohort effect on HBV-related mortality from liver disease and liver cancer, the HBV vaccination program is deemed to have limited or no impact on reducing mortality from chronic hepatitis B (CHB).

In these regards, secondary prevention of hepatocellular carcinoma (HCC) through antiviral therapy for patients with CHB is important and has been simulated to reduce significantly the incidence of HCC in a short-term. 1 However, there are still controversies regarding when to start the treatment and how to treat the patients.

Impact of Widespread Use of Oral Anti-HBV Agents on Population Level HBV management has substantially progressed in Korea since 1999, including successive approval and life-long reimbursement of oral antiviral agents.

The number of patients receiving oral antiviral therapy for HBV precipitously increased since 1999, and the hypothesis th；at this therapeutic approach may increase patient survival has been suggested by several observational studies. In fact, our recent population-based study in Korea demonstrated that mortality from liver disease decreased by >60% from

1999 through 2013 by all measures. 2 In contrast, liver cancer mortality, in terms of absolute number of annual deaths and crude death rate, has significantly increased during the same period. This dissociation of mortality trends between liver disease and liver cancer coincided with the steep increase in annual prescription of oral antiviral agents against HBV and increased life expectancy of patients with liver disease. Our findings imply that marked decrease in liver disease mortality may increase the life expectancy and the number of patients at risk of developing HCC, inadvertently leading to increased HCC incidence and mortality in the population.

These findings suggest that, notwithstanding the wide availability of potent antiviral drugs against HBV and the remarkable reduction in liver disease mortality, the burden of liver cancer would persist for the next several decades.

It was unclear whether the achievement of virologic response (VR) modifies the risk of HCC differently in CHB and chronic hepatitis C (CHC).

Thus, we analyzed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733).3 Among patients with VR, CHB was independently associated with a significantly higher incidence of HCC (HR, 2.17; P=0.003) than CHC. These data suggest that, even with viral suppression with entecavir, the risk of HCC is higher in patient with CHB compared with CHC patients with SVR.

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When to start the treatment?

Chronic infection with HBV progresses through different phases. The first, which is the immune-tolerant (IT) phase, is characterized by high circulating HBV DNA and normal ALT levels.

Antiviral treatment is generally not recommended for these patients by most practice guidelines because of the notion that the histologic activity is dormant, and the risk of disease progression is low in the IT phase.

In our recent cohort study, the clinical outcomes of 413 untreated HBeAg-positive, non-cirrhotic IT phase patients with normal alanine aminotransferase (ALT) levels and high HBV DNA levels (≥20,000 IU/mL) were compared with those of 1497 immune-active (IA) phase patients (ALT ≥80 IU/mL and HBV DNA ≥20,000 IU/mL) treated with nucleos(t)ide analogs.4 The untreated IT group showed a significantly higher adjusted risk of HCC (HR, 2.54; p<0.001) and death/ transplantation (HR, 3.38; p<0.001) than the treated IA group; which was consistently identified through inverse probability treatment weighting, propensity score-matched, and competing risks analyses. Lower HBV DNA levels (but above 20,000 IU/mL) were independently associated with a significantly higher risk of clinical events.

In our another historical cohort study including 5414 HBeAg-negative CHB patients without cirrhosis in Korea from 2000 to 2013, compared with the treated Active phase (HBV DNA ≥2000 IU/ mL and ALT ≥2xULN, n=546) group, the untreated Replicative phase (HBV DNA ≥2000 IU/mL and persistently normal ALT, n=900) group showed a significantly higher risk of HCC (HR 1.76; P=0.05) and death/transplantation (HR 2.14; P=0.03) by propensity score-matched analysis.5 Our results suggest that many unnecessary cancers and deaths could be prevented by earlier antiviral intervention in non-cirrhotic CHB patients with high viral load and normal ALT levels.

Moderate levels of serum HBV DNA and the highest risk of HCC Studies have shown a higher risk of HCC with higher baseline serum HBV DNA levels in CHB patients. However, the association between very high

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HBV DNA levels (>6 log 10 IU/mL) and HCC risk remains unclear, especially in middle-aged and old HBeAg-positive patients. To identify the association between broad-range HBV DNA levels and HCC risk, we conducted a historical cohort study in Korea involving 6949 non-cirrhotic, treatment-naïve CHB patients with alanine aminotransferase (ALT) <2× upper limit of normal for >1 year.6 By multivariable Cox regression analysis, HCC risk was highest with baseline HBV DNA levels of 6–7 log10 IU/mL (adjusted hazard ratio [aHR] 4.98; P<0.001), and lowest with >8 log10 IU/mL (aHR 0.90; P=0.71) and ≤4 log10 IU/mL (aHR 1.00; reference), which was independent of other predictive factors. The similar association between HBV DNA levels and HCC risk was consistently observed in all age subgroups (age <40 years, 40-49 years, and ≥50 years).

These results suggests that extending treatment indication to CHB patients with medium levels of HBV DNA may be considered to further prevent HCC, regardless of ALT levels.

How to treat the patients with CHB? In our historical cohort study of 5374 CHB patients, entecavir therapy was associated with a significantly lower risk of death or transplantation than lamivudine.7 However, the drugs did not have different effects on HCC risk.

Entecavir and tenofovir disoproxil fumarate (TDF) have comparable efficacy in achieving surrogate endpoints including virologic response and are equally recommended as first-line treatments for patients with CHB. However, it is unclear whether they have equivalent impacts on clinical outcomes, especially HCC, in the patients. Therefore, we conducted a nationwide historical population cohort study involving treatment-naïve adult CHB patients who started treatment with entecavir (n=11,464) or TDF (n=12,695) between 2012 and 2014 by using Korean national health insurance service database.8 As a validation, a hospital cohort of CHB patients treated with entecavir (n=1,560) or TDF (n=1,141) in a tertiary referral center between 2010 and 2016 were analyzed. In the population cohort, annual incidence rate of HCC was significantly lower in the TDF group.

2020 消化系聯合學術演講年會

TDF was associated with a significantly lower risk of HCC compared to entecavir in 10,923 pairs of the propensity-score matched population cohort and 869 pairs of the propensity-score matched hospital cohort.

The significantly lower risk of HCC in the TDF group was consistently observed both in the cirrhosis and non-cirrhosis subcohorts of the population cohort, and in the cirrhosis subcohort of the hospital cohort.

The consistent results were found our systematic review and meta-analysis including 15 observational studies, and also in the patients who received curative hepatic resection for HCC.9, 10 Given the poor prognosis of patients who developed HCC, our findings may have considerable clinical implications in the prevention of the cancer in patients with CHB.

Conclusions Our findings emphasize the importance of secondary prevention for HCC, including early initiation of HBV treatment for the patients with high viral load regardless of ALT levels.

References 1. N a y a g a m S , T h u r s z M , S i c u r i E , e t a l .

Requirements for global elimination of hepatitis B: a modelling study. Lancet Infectious Diseases 2016;16:1399-1408.

2. Choi J, Han S, Kim N, et al. Increasing burden of liver cancer despite extensive use of antiviral agents in a hepatitis B virus-endemic population.

Hepatology 2017;66:1454-1463.

3. Kim GA, Han S, Kim HD, et al. Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic

response. J Viral Hepat 2017;24:990-997.

4. Kim GA, Lim YS, Han S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut 2018;67:945-952.

5. Choi GH, Kim GA, Choi J, et al. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther 2019;50:215-226.

6. Kim GA, Han S, Choi GH, et al. Moderate levels of serum hepatitis B virus DNA are associated with the highest risk of hepatocellular carcinoma in chronic hepatitis B patients. Aliment Pharmacol Ther 2020;51:1169-1179.

7. Lim YS, Han S, Heo NY, et al. Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine. Gastroenterology 2014;147:152-61.

8. Choi J, Kim HJ, Lee J, et al. Risk of Hepatocellular Carcinoma in Patients Treated With Entecavir vs Tenofovir for Chronic Hepatitis B: A Korean Nationwide Cohort Study. JAMA Oncol 2019;5:3036.

9. Choi WM, Choi J, Lim YS. Effects of Tenofovir vs Entecavir on Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2020.

10. Choi J, Jo C, Lim YS. Tenofovir vs. Entecavir on Recurrence of Hepatitis B Virus-Related Hepatocellular Carcinoma after Surgical Resection. Hepatology 2020.

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外賓演講（二） TO ELIMINATE HCV INFECTION IN JAPAN Masayuki Kurosaki Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Japan

Nation-wide registry of acute viral hepatitis in Japanese Red Cross liver study group revealed that acute hepatitis C with unknown source of infection still exists. To drastically reduce this kind of new HCV infections and to eliminate HCV, WHO set target to diagnosing 90% of people living with HCV and treating 80% of diagnosed people with direct-acting antivirals (DAAs) by 2030. To achieve this target, we need to overcome various access barriers for HCV antibody testing, linkage to care, and initiation of highly effective DAAs. The first step is HCV antibody testing. Outcome Report (2012) of Hepatitis Examination Taking Status Grasping Program in Japan revealed that top 3 trigger for taking hepatitis virus examination was 1) inclusion of HCV testing in the periodic health checkup, 2) examinations before surgery, during pregnancy/delivery or before endoscopy, and 3) notification of free testing.

For notification, PR magazines, or flyers/pamphlets were helpful. Assistance with financial support and free examination at public health center were factors to motivate early examination.

The second step is linkage to care. National sampling survey on hepatitis virus screening in 2011 revealed that among citizens who had viral hepatitis examinations before surgery, delivery or endoscopy, 30.5% did not correctly recognized that they received HCV screening test, which means that the results of hepatitis virus examination may not be notified correctly to some examinees. To improve this, intrahospital cooperation scheme should be established, and patients should be picked up through alert notification, etc. Among the examinees who understood the examination result correctly, the rate of linkage to continuous HCV care was 85.0%. An important

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step is linkage to hepatology specialists. The uniform scheme of community cooperation between Core hospitals (70 hospitals in 47 prefectures, at least one hospital in each prefecture), Liver disease-specialized medical institutions (3,039 sites, at least one site in each secondary medical region), and local clinics/ hospitals are established in Japan. Core hospitals cooperate, support, and technically guide other medical institutions by suppling medical information related to liver diseases, holding seminars targeting healthcare professionals and community residents, and setting up forums for discussion with specialized medical institutions related to liver diseases.

Another point is a financial support. The law Basic Act on Hepatitis Measures have been developed and the economic assistance has been enriched. A public support scheme is established by the national government and each regional government to reduce medical expenses of patients undergoing treatment of hepatitis C, and the upper limit of self-payment is set at 10,000-20,000 yen (monthly amount).

Thanks to efforts on every step of these access barriers, nation-wide survey revealed obvious decline in hepatocellular carcinoma, and cirrhosis.

The remaining tasks to further accelerate the speed to elimination of HCV within hospital is to facilitate the notification of positive HCV test results to all examinees, and facilitate consultation to hepatologist by intra-hospital cooperation scheme. For elimination outside hospital, continuous education of citizens and general physicians are important, and for this purpose, community cooperation lead by Core-Specialized Hospitals maybe helpful.

2020 消化系聯合學術演講年會

兩性課程 性別議題中的一些迷思與誤解 劉嘉逸 林口長庚紀念醫院

1. 性取向 (sex orientation) 指的是一個人＂喜好的 性別＂，性別認同 (gender identity) 指的是自己 認同的性別。 2. 當代科學認為性取向與性別認同有相當程度的 體質因素，穩定度及不可變性。 3. 精神醫學界自 1987 年起已經把同性戀完全從精 神疾病中排除。2013 年美國精神醫學會精神疾 病診斷與統計手冊第五版 (DSM-5) 以「性別不

悅 (gender dysphoria) 」來取代「性別認同障礙」 診斷名稱，也就是認為：性別認同的差異不再 視為一種或疾病，等同於「性別認同」的「去 疾病化」。 4. 台灣民眾因對性取向與性別認同的不瞭解或誤 解，造成意見分歧，社會對立。本演講從科學 角度，釐清性別議題中的一些迷思與誤解。期 待社會更為和諧。

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2020 消化系聯合學術演講年會

WHO 消化管病理分類─ 臨床與病理的對話 世界衛生組織消化道腫瘤分類新版介紹 鄭永銘 臺大醫院

From 2019, WHO began to publish the 5 th version of classification of tumors. The first book is about the digestive system tumors. Among the many alterations in the classification and diagnostic criteria, the changes most relevant to clinicians are (1)Most precancerous lesions are classified as low-grade or high grade (2)Several new types of gastric adenomas are identified: intestinal type, foveolar type, pyloric gland adenoma, and oxyntic gland adenoma.

(3)Colorectal sessile serrated adenoma is renamed as sessile serrated lesion.

(4)Neuroendocrine neoplasms are classified as neuroendocrine tumors or neuroendocrine carcinoma.

The differentiation is difficult for pancreatic tumors.

Immunostaining for p53, Rb, ATRX, and DAXX may

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be helpful.

(5)Oncocytic IPMN is separated from other types of IPMN and renamed as Intraductal oncocytic papillary neoplasm based on genetic findings (6)Intrahepatic cholangiocarcinoma is classified as small duct and large duct type. The former is associated with viral hepatitis and more likely to harbor FGFR2 translocation and IDH mutations.

(7)Intraductal papillary neoplasm of the bile duct is classified as type I and type II. Type I is similar to IPMN of the pancreas. Type II is intraductal carcinomatosis.

(8)Gallbladder adenoma is classified as pyloric gland adenoma and intracholecystic papillary neoplasm (IPCN). IPCN is frequently associated invasive carcinoma.

2020 消化系聯合學術演講年會

WHO 消化管病理分類─ 臨床與病理的對話 腸胃科與病理科的對談之內視鏡醫師觀點 - 大腸腫瘤 張立群 臺大醫院

Histological diagnosis plays an essential role in deciding on treatment and surveillance. An inappropriate histological diagnosis may lead to either over- or under-treatment for patients and subsequently influence the life quality or safety of patients. Through the conversation between pathologists and clinicians, the histological diagnosis will more satisfy the clinical need and maximize the benefit of patients.

With the implementation of colorectal cancer (CRC) screening, more and more early cancers, including T1 cancer, are diagnosed. Thus, how to treat T1 cancer becomes a critical issue. T1 cancer with the risk of lymph node metastasis (LNM) should be treated with surgery. In contrast, T1 cancer without risk of LNM could be resected by endoscopy alone. Given the risk of LNM largely depends on the histological diagnosis, histology with sufficient information is essential for making the strategy to treat T1 cancer. Sessile serrated lesion (SSL) accounts for 15 to 20% CRC and is an crucial pre-cancerous lesion.

Because the subjects with SSL carry a higher risk of CRC, it is critical to provide adequate surveillance for these patients. The surveillance interval recommended by the current guidelines varies with the presence of cytological dysplasia in SSL. Thus, the comprehensive histology report of SSL should include the presence of cytological dysplasia, either low-grade or high-grade.

A histology report with sufficient information will help in improving the quality of medical care.

A clear description of advanced histology will avoid under-treatment for subjects with the risk of LNM. A histology report mentioning the presence of cytological dysplasia will help to provide an adequate surveillance interval for subjects with SSL and minimize the risk of CRC. The manuscript has revised according to the previous comments. Please discard the multivariable analysis without age and gender in Table 2. In addition, please switch the term of univariate to univariable.

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2020 消化系聯合學術演講年會

專題討論（一） Application of Artificial Intelligence in Gastrointestinal Diseases AI-ASSISTED COLONOSCOPY – IS IT PRIME TIME TO USE IN CLINICAL PRACTICE? Yuichi Mori Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan

It is broadly known that endoscopists miss around 20%-40% polyps during colonoscopy and many endoscopists cannot identify neoplastic change of colorectal polyps with a >90% accuracy.

Artificial intelligence (AI) technology is catching attention as an attractive measure to overcome these limitations which inherently exist in colonoscopy practice. AI tools designed to help colonoscopy practice can be largely classified into three categories; 1. polyp detection, 2. prediction of poly pathology, 3. prediction of invasion depth of colorecta cancer.

Colonoscopy is the hottest area of research in the

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field of AI in endoscopy; multiple prospective studies including six randomized control trials have already been reported, most of which provided supportive data for the use of AI. On top of that, multiple AI tools for colonoscopy have already been on the market of several countries. Therefore, understanding of current situation of AI tools for colonoscopy may contribute to improvement of quality of next-generation colonoscopy. In this presentation, we would like to go over the current status of research and development in AI for colonoscopy and share some of the challenges we are facing in this field.

2020 消化系聯合學術演講年會

專題討論（一） Application of Artificial Intelligence in Gastrointestinal Diseases AI APPLICATION OF CAPSULE ENDOSCOPY IN SMALL BOWEL DISEASE 許振銘 林口長庚紀念醫院

Capsule endoscopy (CE) is a useful noninvasive tool for examination of small bowel. CE is recommended as the first-line investigation in patients with obscure gastrointestinal bleeding.1 About 55,000 to 86,000 frames are recorded during an examination for a small bowel (SB) CE. Therefore, interpretation of SB-CE is tedious and time-consuming task that usually lasts 45–90 min and requires the continual concentration of the endoscopists. 2 However, this process is prone to missing lesions as a result of the limited ability of human attention. The SB-CE miss rates for vascular lesions, ulcers and neoplasms were reported up to 5.9%, 0.5% and 18.9%, respectively.3 Some computational software, such as suspected blood indicator , quick view mode, express view mode, adjust mode, omni-selected mode, red assist mode have been installed to decrease the frames for reading. Although the reading time of capsule films was reduced, the possibility of missing lesions should be concerned.

Due to the progress of artificial intelligence (AI), a number of rule-based and conventional machine learning algorithms have been developed for the CE analysis. Recently deep learning-based approaches demonstrated better performance than conventional machine learning in the domain of medical imaging.4 Several methods based on deep learning have been reported for localization, scene classification, and various lesions (such as bleeding, polyp, hookworm, and angioectasia) detection for CE. 5 For detecting bleeding or hemorrhaging, deep learning– based

approaches have demonstrated 99.9% accuracy for 2,850 positive images and 100% accuracy for 390 positive images. 6,7 A convolutional neural network (CNN) based sematic segmentation algorithm was proposed to detect gastrointestinal angioectasia (GIA)

by Leenhardt el al.8 From 200 capsule endoscopies, 600 normal frames and 600 frames with angioectasias were extracted for training and testing. This algorithm yielded a sensitivity of 100% and a specificity of 96% for detection of GIA. For detecting polyps, Yuan et al proposed a stacked sparse autoencoder– based approach.9 This algorithm achieved an accuracy of 98% for 4,000 images from 35 patients. For detecting hookworms, He et al reported a novel edge extraction network to capture their characteristics.10 The accuracy and sensitivity of the proposed network were 88.5% and 84.6%, respectively. Ding Z and Shi H et al reported a CNN-based auxiliary reading system for differentiating abnormal frames from normal frames in SB-CE examination.11 The system identified abnormalities with 99.88 % sensitivity in the per-patient analysis and 99.90% sensitivity in the per-lesion analysis. The reading time by CNN-based auxiliary system was 5.9 +/- 2.23 minutes.

Essential progress in the development of AI application for CE can be achieved by sharing data and knowledge, together with close collaboration between medical and information technology scientists.12 In the near future, AI will play an important role in the field of CE.

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References 1. Pennazio M, Spada C, Eliakim R, et al. Smallbowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 2015;47:352–376.

2. Koulaouzidis A, Rondonotti E, Karargyris, A. Small-bowel capsule endoscopy: a ten-point contemporary review. World J Gastroenterol 2013;19:3726–3746.

3. Lewis B, Eisen G, Friedman S. A pooled analysis to evaluate results of capsule endoscopy trials.

Endoscopy 2005; 39; 303–308.

4. Shvets A, Iglovikov V, Rakhlin A, Kalinin AA. Angiodysplasia detection and localization using deep convolutional neural eetworks. 2018 17th IEEE International Conference on Machine Learning and Applications (ICMLA); doi:10.1109/ ICMLA.2018.00098 5. Hwang Y, Park J, Lim YJ, Chun HJ. Application of artificial intelligence in capsule endoscopy: where are we now? Clin Endosc 2018;51:547-551.

6. Jia X, Meng MQH. A deep convolutional neural network for bleeding detection in wireless capsule endoscopy images. In: 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC); 2016

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Aug 16-20; Orlando (FL), USA. Piscataway (NJ): IEEE; 2016:639-642.

7. Li P, Li Z, Gao F, Wan L, Yu J. Convolutional neural networks for intes- tinal hemorrhage detection in wireless capsule endoscopy images. In: 2017 IEEE International Conference on Multimedia and Expo (ICME); 2017 Jul 10-14; Hong Kong, China. Piscataway (NJ): IEEE; 2017:1518- 1523.

8. Leenhardt R, Vasseur P, Li C, et al. A neural network algorithm for detection of GI angiectasia during small-bowel capsule endoscopy. Gastrointest Endosc 2019;89:189-194.

9. Yuan Y, Meng MQ. Deep learning for polyp recognition in wireless capsule endoscopy images.

Med Phys 2017;44:1379-1389.

10. He JY, Wu X, Jiang YG, et al. Hookworm detection in wireless capsule endoscopy images with deep learning. IEEE Trans Image Process 2018;27:2379-2392.

11. Ding Z, Shi H, Zhang H, et al. Gastroenterologistlevel identification of small-bowel diseases and normal variants by capsule endoscopy using a deep-learning model. Gastroenterology 2019;157:1044-1054.

12. Iakovidis DK, Koulaouzidis A. Software for enhanced video capsule endoscopy: challenges for essential progress. Nat Rev Gastroenterol Hepatol 2015;12:172-186.

2020 消化系聯合學術演講年會

專題討論（一） Application of Artificial Intelligence in Gastrointestinal Diseases DIGITAL PATHOLOGY IN GI: WHERE ARE WE NOW? 梁文議 臺北榮民總醫院

Nearly one year after the FDA cleared the Philips IntelliSite Pathology Solution for primary diagnosis, there are getting more and more innovative pathology labs are working 100 percent with digital pathology for their current pathology workload. But large-scale adoption in the world may await a few remaining solutions and steps, among them next-generation scanning systems, improved viewing software, solid infrastructure, and an open versus a closed system

approach. Full acceptance of the power of artificial intelligence could well be the biggest push of all.

In this section, we will introducing the development of digital pathology, discuss the pros and cons of transforming primary diagnosis using traditional microscopic diagnosis into digital whole slide images, and the AI application developing in GI pathology past, current and future.

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2020 消化系聯合學術演講年會

專題討論（一） Application of Artificial Intelligence in Gastrointestinal Diseases CAN AI FULFILL UNMET CLINICAL NEED IN GASTROENTEROLOGY? 邱瀚模 臺大醫院

Advances in artificial intelligence (AI) technology represent an opportunity to benefit gastroenterological practice and identifying unmet clinical need is the key to the development of medical AI tool. Most of the research of AI in gastroenterology have been applied in endoscopy in past years but recently it has also been applied in the prediction of disease outcomes using large datasets. Deep learning algorithms are now also applied in upper GI bleeding for identifying patients at higher risk of repeat bleeding; detection of pancreatic cancer using EUS or CT images in combination with biomarkers; outcome prediction in acute pancreatitis, prediction of outcomes of liver cirrhosis applying imaging data and HER, or guiding treatment in IBD, etc. It can also be used to help doctors in managing tedious yet important clinical tasks and audit the

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quality of clinical practice. In the future, applying AI with integration of multi-omics (genomics, clinomics, microbiomics, radiomics in predicting patient outcomes in GI disorders is anticipated.

The limitations of AI techniques that require caution include the diversity of quality of datasets for machine-learning development and many AI tools published in literatures have yet been validated in real-world clinical setting. Moreover, deep learning algorithms are considered to be black-box models, in which it is difficult to understand decision-making processes, preventing physicians from finding potential confounding factors. Ethical consideration is also important and AI is not aware of the patient’s preferences or legal liabilities.

2020 消化系聯合學術演講年會

專題討論（二） HCV Elimination in Community HCV MICRO ELIMINATION IN PRISONERS 鄭健禹 衛福部桃園醫院

Chronic hepatitis C is an important cause of liver-related morbidity and mortality worldwide.

Intravenous drug users (IVDU) are at an increased risk of hepatitis C (HCV) and are also overrepresented within the correctional facilities. The global prevalence of HCV antibody among the prison population estimated to be 26%, and 64% of them reported a history of IVDU. The seroprevalence of chronic HCV infection in correctional facilities ranged from 16% to 49%. Injection drug users are criminalized in Taiwan, and 28,320 people (88% male, 12% female) were found guilty of drug crime.

Of them, 78.6% were aged between 30 and 50 years old in 2017. There were 1,899 people living with human immunodeficiency virus (PLHIV) in detention centers (out of a total of 56,560 detained persons) taken care by different HIV designated hospitals, and IVDU population accounted for 19.5% (n = 7,023) of all diagnosed HIV-infected subjects in Taiwan.

The overall prevalence of HCV infection among HIV-infected IDUs was 96.6%. Unfortunately, HIVinfected prisoners with chronic HCV infection have fewer opportunities to receive treatment than the same patients in community setting. Thus, a health burden of liver-related morbidities is significant in

patients within correctional systems. Few studies have been conducted on the treatment of pegylated interferon (Peg-IFN) plus ribavirin (RBV) in chronic hepatitis C-infected prisoners, and some convincing results were observed. Canadian penitentiaries using standard interferon plus ribavirin were with an overall sustained virologic response (SVR) of 55.9% (31.6% for genotype 1, 100% for genotype 2 and 71.4% for genotype 3). Maru et al. also showed an overall SVR to Peg-IFN plus ribavirin of 47.1% (43.1% for HCV-genotype 1 and 58.8% for HCV-genotypes 2 and 3). In Taiwan, Cheng CH et al. showed that treatment response among incarcerated patients with HCV infection demonstrated conclusive evidence (overall SVR of 84.5%, 70.8% for genotype 1, 94.1% for genotype non-1). Although most direct-acting antiviral agents (DAAs) are now reimbursed by the national health insurance administration in Taiwan since January 2017 with outstanding efficacy over 90%-100% and few adverse effects, the accessibility of DAAs is still limited at most prisons. HCV microelimination in prisoners will be one of most important step to achieve HCV elimination in Taiwan by 2025.

Therefore we have to conduct some effective and practical methods to accomplish our goal.

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2020 消化系聯合學術演講年會

專題討論（二） HCV Elimination in Community HCV MICRO ELIMINATION IN ESRD 黃釧峰 高雄醫學大學附設醫院

Hepatitis C virus (HCV) infection may deteriorate renal function and in turns lead to end-stage renal disease (ESRD). On the other hand, uremic patients on maintenance hemodialysis (HD) are at great risk for HCV infection. Compared to non-HCV infected subjects, uremic patients with HCV infection have higher risk of liver and non-liver related morbidities and mortalities. Anti-HCV therapy at individual patient level may improve long-term outcome.

However, there exists a huge gap of controlling HCV infection in the population level. In addition to the inadequate treatment efficacy and tolerability, inaccurate HCV diagnosis and poor accessibility led to a very poor HCV treatment uptake of the uremic population in the interferon era. The emerging innovation of all-oral directly acting antivirals

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(DAAs) have led to a sustained virological response rate of > 95 % in the majority of populations including patients with chronic kidney disease. Nevertheless, the treatment of chronic hepatitis C (CHC) in the uremic population remains underutilization even the DAA era.

World Health Organization (WHO) sets an ambitious goal of HCV elimination worldwide by 2030. The concept of microelimination toward HCV infection would be a more efficient and practical approach to achieve the goal. Due the high prevalent and contiguous property in the close-contact environment, the uremic populations should be the priority of HCV microelimination. To scale up the prevention and treatment of HCV, an outreach strategy or straight forward linking-to-care would be the key determinant to overcome the hurdle of HCV care cascade.

2020 消化系聯合學術演講年會

專題討論（二） HCV Elimination in Community HCV MICRO ELIMINATION IN PWID/MSM 蘇維文 彰化基督教醫院

Hepatitis C virus (HCV) is a major public health threat in Taiwan community. To accomplish the 2025 goal of HCV micro-elimination in Taiwan, we need to acknowledge that unidentified HCV infected patients especially in special population like people who inject drugs (PWID)/men who have sex with men (MSM) can be the reservoir of ongoing HCV transmission and hinder our way to success.

In high-income countries, HCV is primarily transmitted amongst PWID. Treating PWID with HCV infection is an essential component of achieving the WHO HCV elimination target and is adopted as “treatment as prevention “strategy along with “Harm reduction program with safe needle exchange”. Recent evidence highlights that recently PWID treated with DAAs consistently complete treatment and obtain high rates of SVR and largely avoid early reinfection.

Hence, we should treat PWID HCV infected patients to eliminate continuous HCV transmission especially in this special population.

Recent studies strongly suggest that HCV is transmitted via sexual contact in HIV-positive MSM and more recently in HIV-negative MSM eligible

for or on pre-exposure prophylaxis (PrEP). The reinfection risk following HCV clearance is about 10 times the risk of primary infection. Some of these networks might overlap with networks of PWID further highlight the importance of “treatment as prevention” strategy in both of these two special populations.

The precise mechanisms facilitating sexual transmission remain unclear. Damage to the mucosal barrier in the rectum could increase susceptibility.

Mucosal dendritic cell subsets could increase HCV susceptibility by retaining HCV and transmitting the virus to other cells. Hence, educate to avoid high-risk sexual behavior should be provided to this special population.

Since HCV reinfection can both occur in these two special populations, at least annually HCV RNA testing (and risk based, if indicated) for continuous surveillance of new reinfection is recommended according to HCV AASLD/IDSA guideline after successfully treated or spontaneously cleared HCV infection.

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2020 消化系聯合學術演講年會

專題討論（二） HCV Elimination in Community HCV MICRO ELIMINATION IN HYPERENDEMIC AREAS 張德生 嘉義長庚紀念醫院

The prevalence of HCV infection is estimated to be 1% to 3% in Taiwan, whereas it is as high as 6% to 30% in southern Taiwan. Yunlin and Chiayi are among the most HCV prevalent counties in southern Taiwan. This high prevalence in these regions is primarily attributed to infections through iatrogenic routes due to local individuals’ medicalseeking behaviors and the use of folk remedies, such as acupuncture and cutting of the skin with inadequately sterilized devices before 1960s. Patients in hyperendemic areas are generally old in age and reside in remote sites. Due to old age, this generation of HCV patients in these hyperendemic areas will wither naturally in 20-30 years even without specific intervention, making future HCV prevalence pattern in Taiwan similar to western countries with concerns on high risk populations. The major aim of HCV

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elimination in these hyperendemic areas is therefore for secondary prevention of liver disease sequelaes in addition to blocking transmission routes. The pattern of disease prevalence in these hyperendemic areas makes it hard to achieve the goal of disease awareness in > 90% of patients. Nevertheless, HCV elimination would absolutely reduce liver-related mortality in these hyperendemic areas. Most of the current HCV prevention and treatment funds in Taiwan are used for expensive treatment drugs. HCV cannot be eliminated only for medical treatments confined to medical institutions. The next critical step for HCV elimination should focus on outreach screening and linkage to accessible therapy, especially in the hyperendemic areas. I will present our experiences in trying to eliminate HCV in remote hyperendemic areas in Yunlin and Chiayi counties.

2020 消化系聯合學術演講年會

專題討論（三） Fecal Microbiota Transplantation (FMT) of the Current Situation and the Future THE FECAL MICROBIOTA TRANSPLANTATION (FMT): SHARING AND COMMUNICATING EXPERIENCE FROM DIVISION OF GASTROENTEROLOGY 許文鴻 高雄醫學大學附設醫院

The distal gastrointestinal tract contains a large and diverse array of microorganisms with more than 1014 bacteria of more than 1000 species. The balances between the intestinal microbiota with humanity play a role the maintenance of healthy state. There is emerging evidence that gut microbiota dysbiosis is associated with the pathogenesis of both intestinal and systemic disorders such as Clostridium difficle infection, inflammatory bowel disease, metabolic syndrome, cardiovascular disease and neurologic disorder.

Gut microbiota manipulation by fecal microbiota transplantation, the infusion of fecal solution from a healthy donor into the intestinal tract of illness recipient, could be a promising therapeutic strategy for disease related to intestine dyspbiosis. In past decade, high efficacy of FMT in recurrent Clostridium difficle infection have proved this theory and investigation of its potential applicaion is ongoing worldwide.

Here, we review the methology, safety and its clinical application of FMT.

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2020 消化系聯合學術演講年會

專題討論（三） Fecal Microbiota Transplantation (FMT) of the Current Situation and the Future THE FECAL MICROBIOTA TRANSPLANTATION (FMT): SHARING AND COMMUNICATING EXPERIENCE FROM DIVISION OF PEDIATRICS 陳建彰 林口長庚紀念醫院

Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s gut microbial composition and confer a health benefit. Fecal transplant has emerged as a remarkably effective and safe alternative for patients with recurrent or refractory Clostridium difficile infection (CDI) unresponsive to standard antibiotic regimens, with a cure rate of at least 80%. There are preliminary indications to suggest that it may also carry therapeutic potential for other conditions such as inflammatory bowel disease (Crohn’s disease or ulcerative colitis), obesity, DM, metabolic syndrome, and functional gastrointestinal disorders.

The pediatric patients considered for FMT for refractory or recurrent CDI at our hospital complete an informed consent for the FMT procedure. The donor was usually a close relative, frequently a parent or sibling; another unrelated donor stool was used for one recipient. Screening labs for the stool donors include serum examination and multiple stool testing as well as stool culture. The efficacy could be improved by carefully selecting younger donors such as college and high school students on the basis of their relatively healthier gut microbiota content. Screening donated fecal material for antibiotic-resistant microorganisms was also suggested. In the procedure of FMT, the donor was instructed to collect feces (about 30gm) in a small container and to bring it to our hospital. Then we filtered the mixed fecal contents, resulting in one bottle of 250 ml fecal microbiota suspension. The fecal suspension was administered into the intestine

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of the recipient via colonfibroscope. After FMT, the recipient got improved in clinical symptoms, including relief of abdominal distension, diarrhea (soft to form stool), and increase feeding amount as well as weight gain.

In our hospital, multiple fecal specimens including donor and recipient of fecal microbiota transplant were analyzed by next generation sequencing. Individual microbial diversity and composition were analyzed via PCR and sequencing were performed using a modified version adapted for the Illumina MiSeq. Briefly, the V4 region of the 16S rRNA gene would be amplified with region-specific primers that included the Illumina flowcell adapter sequences.

A comparison of the taxonomic data revealed that the children with CDI exhibited relatively high abundances of Proteobacteria and Fusobacteria at the phylum level and a relative underrepresentation of the phylum Bacteroidetes and Firmicutes. At the genus level, we observed significant increases in the numbers of Escherichia, Sutterella, and Fusobacterium in the CDI. After fecal microbiota transplant, we found significant increase in the relative abundance of the phylum Bacteroidetes and Firmicutes (possible come from donor) in the feces of recipient.

Our study showed that fecal microbiota transplant can improve the microbial dysbiosis of the recipient with an increased diversity of gut microbiota. FMT may be considered a potentially useful therapy for additional conditions in the future. Ongoing clinical trials will continue to provide insight into this growing field.

2020 消化系聯合學術演講年會

專題討論（三） Fecal Microbiota Transplantation (FMT) of the Current Situation and the Future THE FECAL MICROBIOTA TRANSPLANTATION (FMT): HOW TO CHOOSE THE MOST APPROPRIATE DONORS? 吳俊穎 臺北榮民總醫院

Since September 6, 2018, fecal microbiota transplantation (FMT) has become a legal health care practice under the special regulation of Medical Act 62. FMT has become one of the standard therapies to treat recurrent or refractory Clostridium difficile (rCDI) and the therapeutic effect is excellent. Metaanalysis of clinical trials of FMT in treating rCDI reported more than 80% successful rate with only once FMT and more than 90% successful rate with repeated FMT. In addition to rCDI, many other indications, such as inflammatory bowel diseases, metabolic syndrome, neurological diseases, etc., are under clinical trials to examine the efficacy of FMT. Although FMT is very effective to cure rCDI and also very promising to treat other diseases, how to choose the most appropriate donors is always

a challenge. The most appropriate donors can be defined in two levels, the safety issue and the efficacy issue. For the safety issue, Taiwan Fecal Microbiota Transplantation Consensus, which was made by Taiwan Microbiota Consortium in March, 2018, has a strict regulation to screen the appropriate donors. The donors must fulfill all the criteria including history, blood and stool tests, to have the chance to donate their feces for FMT delivery. For the efficacy issue, finding the appropriate donors is the effort to find the super donors with most excellent treatment responses.

Recent studies have suggested several characteristics of the donors are associated the treatment outcomes.

In the present study, the most recent advances in this issue will be discussed.

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2020 消化系聯合學術演講年會

專題討論（三） Fecal Microbiota Transplantation (FMT) of the Current Situation and the Future THE FECAL MICROBIOTA TRANSPLANTATION (FMT): POSSIBLE INDICATIONS AND FUTURE DIRETIONS 吳明賢 臺大醫院

Advances in high-throughput microbial genomic sequencing and systems biology have provided novel insights into the role of gut microbiota in health and diseases. Although whether alterations in gut microbiota are cause, consequence, or incidental to disease remains largely unknown, restoration of the gut microbiota by fecal microbiota transplantation (FMT) is becoming a growing therapy for a variety of indications. FMT has a well-established role in the treatment of recurrent Clostridium difficile infection (CDI), given its high efficacy and a favorable shortterm side effect profile. In addition to CDI, FMT has been tested in inflammatory bowel disease, irritable bowel syndrome and graft vs. host disease after

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allogenic hematopoietic stem cell transplantation.

Beyond gastrointestinal tract, FMT has also been explored for hepatic encephalopathy, cirrhosis, cardiometabolic syndrome, central nervous system diseases (multiple sclerosis, Parkinson disease, autism), cancers and so on. As the application of FMT expands, awareness of adverse effects, methodologic and ethical issues is emerging. Furthermore, FMT is not a one-size-fit-all strategy, and future studies are warranted to identify components of the microbiota that have specific effects in patients with different disease. This includes determination of active components of FMT to develop microbe-based precision medicine.

2020 消化系聯合學術演講年會

專題討論（四） Current Application of Human Tissue and Pluripotent Stem Cell in GI Tract-Possibility and Challenge THE CURRENT, CLINICAL AND CHALLENGE OF HUMAN ES AND IPSC 何弘能 臺北醫學大學

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are expected to have several clinical applications, including the studies of disease mechanism, drug screening and regenerative medicines. However, these clinical applications are still limited due to several critical challenges.

We have published several articles about how to differentiate human oocytes using human embryonic stem cells and hiPSCs from normal subjects and patients with premature ovarian failure. Oocyte like structure with meiosis and functional granulosa

cells were also established. Disease specific hiPSCs can serve as the platforms to study the mechanism, progression and potential drug screening for a particular disease. Some of our primitive results from Pompe disease, left ventricle non-compaction cardiomyopathy and polycystic ovarian syndrome identified several possible drugs that could effectively modifythe pathophysiology of these diseases. Through the differentiation of these disease specific hiPSCs into oocytes, granulosa cells, endothelial cells and cardio-myocytes offered us futher to study their disease mechanism.

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2020 消化系聯合學術演講年會

專題討論（四） Current Application of Human Tissue and Pluripotent Stem Cell in GI Tract-Possibility and Challenge MODELING HUMAN GASTROINTESTINAL DEVELOPMENT AND DISEASES WITH STEM-CELL DERIVED ORGANOIDS 沈家寧 中央研究院

Gastrointestinal (GI) tract responsible for the food digestion and nutrient absorption includes the stomach, the small intestine and the large intestine. Disorders in the stomach and intestine can lead to various GI diseases. During the last few decades, a great effort has been made to understand morphogenesis and development of the GI tract utilizing various animal models. However, species differences in embryonic development and architecture of the adult GI tract are nonnegligible, which make animal models suboptimal for studying GI diseases. The underlying pathogenic mechanisms of many GI diseases remain to be determined.

Organoids are three-dimensional (3D) cell aggregates derived from somatic stem cells or pluripotent stem cells in vitro that are capable of self-renewal and form self-organizing structures. Because organoids develop following intrinsic developmental program, the resultant tissue morphology recapitulates organ architecture with remarkable fidelity. Organoids can therefore be utilized examine disease mechanisms and study organ development.

GI organoids have been used not only to elucidate the mechanisms underlying human GI tract development, but also to model human GI diseases including inflammatory bowel diseases (IBD) and malignancies in GI tract. For example, epithelial organoids derived from patients with IBD can be

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used to determine if Paneth cell degranulation is involved in the pathogenesis of IBD. Our recent work utilizing organoids cultures revealed luminal galectin-9-Lamp2 interaction promotes lysosome stabilization and facilitates autophagy to prevent intestinal pathogenesis. Colorectal cancer (CRC) is the third most common type of cancer and the fourth leading cause of cancer-related deaths worldwide. Yao et al. recently generated a patient-derived organoid (PDO) biobank from patients with locally advanced rectal cancer (LARC) and reported that organoids had similar molecular profiles to those of the patient tumor and that PDOs can predict LARC patient chemoradiation responses, reinforcing their value as a companion diagnostic tool in LARC treatment.

Since organoids derived from induced pluripotent stem cells (iPSCs) can recapitulate 3D architecture of GI tract. Our ongoing work has generated iPSCderived colonic organoid to study cancer initiation and progression in colon. We found that expression of oncogenic driver gene-mutant Kras can altere cyst structure, enhance proliferation rate and generate resistance to Lapatinib. My lecture will summarize the currently available methods to generate GI organoids, particularly those aimed at modelling GI diseases, and provide an overview of the capabilities and limitations of organoid technologies.

2020 消化系聯合學術演講年會

專題討論（四） Current Application of Human Tissue and Pluripotent Stem Cell in GI Tract-Possibility and Challenge PRECISION MEDICINE: CELLULAR PHARMACOKINETIC CONSIDERATIONS FOR CELL THERAPY 林泰元 臺大醫學院

In the field of cell therapy, the application of cells to treat diseases is not only regarded as “a treatment protocol”, but considers the cells as a medical product: “the cell drugs”. However, in contrast to the drugs as small molecules, which have been regulated by the well-established evaluation process of preclinical pharmacokinetic/ pharmacodynamic (PK/PD) studies in order to apply for investigational new drug applications (IND) and new drug applications (NDA), methods used to assess the bio-distribution of transplanted cells and related metabolic information and therapeutic effect mechanisms are still limited. Our study demonstrated that fluorescent nanodiamond (FND) labeling techniques of cells toward accurate quantification

and bio-distribution for cell-transplantation in PK/PD studies may substitute for radiographic calibration, Q-PCR and immunohistochemical analysis for PK/PD in preclinical animal studies. FND has the properties of strong biocompatibility, non-toxicity, low chemical activity and stable optical properties. The technique can be applied to different kinds of immune cells, stem cells, and any other cells used for cell therapy. Taken altogether, transplanted cells by FND labeling can be accurately located and quantified for the distribution of experimental animals in vivo, and the techniques will provide the essential information regarding cellular PK/PD evaluation in preclinical studies of cell therapy to assist in the IND process for cell drug development.

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2020 消化系聯合學術演講年會

專題討論（四） Current Application of Human Tissue and Pluripotent Stem Cell in GI Tract-Possibility and Challenge HUMAN GENE THERAPY IN IPS/ORGANOIDS FOR GI DISEASE 橫山一成 高雄醫學大學

Three-dimensional (3D) organoids are useful to study the molecular mechanisms of the interaction of cancer stem cells (CSCs) with niches and to develop new therapeutic drugs as tissue-replacing complements. CSCs have both stemness properties and oncogenic potential, but no established molecular evidence has explained the interrelationship in stem cells and CSCs. The molecular mechanisms of clonal expansion and cell plasticity in stem cells and CSCs should be clarified to understand the commitment and progression of cancer. Previously we showed that the homeobox gene HOXA13 was required for the development of gastric cancer and as a novel tumor prognostic marker of the oncogenic function in gastric cancers (Oncotarget 2016; Stem cells 2016; 2017).

In contrast, reprogrammed induced pluripotent stem cells (iPSCs) generated from gastric cancer cells repressed the oncogenic phenotype significantly. This antioncogenic function of the HOXA13 in iPSCs is different from the function in cancer cells. We also found that this differential regulation of the HOXA13 gene seems to be controlled by long noncoding RNAs (lncRNAs), such as HOXA transcript at the distal tip

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(HOTTIP) and HOX transcript antisense intergenic RNA (HOTAIR). The molecular target of HOXA13 and HOTTIP/HOTAIR is BMP7 (Stem cells 2017).

However, the precise molecular mechanism underlying the interaction between lncRNAs-HOXA13-BMP family in 3D organoids, and how iPS inducers, such as JDP2 and OCT4, reprogram gastric cancer cells to obtain stemness and oncogenic characters, remain unknown (Oncogene 2017, 2019, EMBO Reports 2019, Scientific Rep 2020). To explore the role of CSCs and BMP signaling using 3D organoids, the researchers now used some editing techniques using CRISPR/Cas9 and others. However, the initial hit for cancer development is the mutation of TP53 gene.

Here I introduce the recombinant virus vector and the mutation frequency of TP53 gene in recombinant adenovirus for human gene therapy. The mutation sites of TP53 are different from the oncogenic mutation sites, especially DNA binding sites. We also show the methods to detect the unknown mutation of TP53 gene. This caution will give us a universal background for human gene therapy to avoid the mutation of TP53 for human gene therapy.

2020 消化系聯合學術演講年會

專題討論（四） Current Application of Human Tissue and Pluripotent Stem Cell in GI Tract-Possibility and Challenge CELL THERAPY FOR LIVER DISEASES: AN UPDATE 李光申 國立陽明大學

Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immunosuppression.

There is increasing evidence to suggest the bone marrow is a transplantable source of hepatic progenitors. We found that multipotent bone marrowderived mesenchymal stem cells differentiate into functional hepatocyte-like cells with almost 100% induction frequency under defined conditions, suggesting the potential for clinical applications.

To effectively induce hepatic differentiation, we designed a novel 2-step protocol with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time-dependent manner. Differentiated cells further demonstrated in vitro functions characteristic of liver cells, including albumin production, glycogen storage, urea secretion, uptake of low-density lipoprotein, and phenobarbital-inducible cytochrome P450 activity. We have further critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases. It was found that mesenchymal stem cells can effectively rescue experimental liver failure and contribute to liver regeneration and offer a potentially alternative therapy to organ transplantation for treatment of liver diseases.

Recently, induced pluripotent stem cells (iPSCs) derived from the reprogramming of somatic

fibroblasts, have been shown to resemble embryonic stem cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes. Thus, iPSCs could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient-specific disease modeling.

Here, we describe an efficient and rapid three-step protocol that is able to rapidly generate hepatocytelike cells from human iPSCs. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC-derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low-density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocytelike cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficient mouse model. In conclusion, this rapid and efficient differentiation protocol that is able to generate functional hepatocyte-like cells from human iPSCs and may offer an alternative option for treatment of liver diseases.

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2020 消化系聯合學術演講年會

專題討論（五） Recent Advances and Future Challenges of IO in GI Cancers GASTRO-ESOPHAGEAL CANCER 吳宜珍 高雄醫學大學附設醫院

The incidence of esophageal cancer, mainly squamous cell carcinoma (SCC), increased rapidly among Taiwanese men while new cases of gastric cancer decreased in the past few decades.

Chemoradiotherapy with or without surgery is the mainstay treatment for locally advanced esophageal and gastroesophageal junction (GEJ) cancer.

However, responses to palliative chemotherapy are limited. Clinical trials on immune checkpoint inhibitors, targeting programmed death-1 (PD-1; eg. nivolumab, pembrolizumab), PD-ligand 1 (PDL1) or CTLA-4 have shown promising activity in esophageal and gastric cancers. According to the phase 3 studies, nivolumab monotherapy represents a potential new standard 3rd-line and 2nd-line treatment option for patients with advanced gastric/ GEJ cancer (ATTRACTION-2) and esophageal SCC (ATTRACTION-3). For heavily treated esophageal

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cancer, the effect of pembrolizumab is better in SCC than in adenocarcinoma (KEYNOTE-180). In the ongoing phase 3 trial (KEYNOTE-181), the effect of pembrolizumab is better than chemotherapy in patients with esophageal SCC or with tumor PDL1 CPS ≥10. Phase 2 studies also shows promising results combining nivolumab with chemotherapy i n g a s t r i c / G E J c a n c e r ( AT T R A C T I O N - 4 , ongoing). Pembrolizumab is effective as 3rdline (KEYNOTE-059, phase 2), but not 2nd-line therapy (phase 3 KEYNOTE-061, compared with paclitaxel) for advanced gastric/GEJ cancer with PDL1 combined positive score (CPS) > 1. Responders to immunotherapy may enjoy sustainable effects, but, there is still no reliable biomarker to predict the response. Moreover, physicians should be careful about possible side effects including interstitial lung disease, colitis and endocrinopathy.

2020 消化系聯合學術演講年會

專題討論（五） Recent Advances and Future Challenges of IO in GI Cancers MSI-H AND OTHER GI CANCERS 林鵬展 成功大學醫學院附設醫院

The status of MSI (microsatellite instability), High or Stable (MSI-H or MSS) is the patients with /without the presence of cancer tissue microsatellite instability. Microsatellite instability (MSI) is a genetic mutation that occurs in short, repeated DNA sequences (microsatellites) and the condition of gene hypermutability that results from impaired DNA mismatch repair (MMR)defect. They can result in the development of various cancers and is most commonly associated with GI cancer caused by MSI include: Colon adenocarcinoma (19.7%) Stomach adenocarcinoma (19%) Rectal adenocarcinoma (5.7%) Esophageal carcinoma (1.67%) Cholangiocarcinoma (1.35%) Pancreatic cancer (<1%)

As a first-line regimen for patients with mCRC with MSI-H, the combination of nivolumab and lowdose ipilimumab yielded an objective RR rate of 64%, a CR rate of 9%, and a DCR rate of 84%, in CheckMate 142 trial. The phase II KEYNOTE-158 study of pembrolizumab in patients with advanced non colorectal MSI-H cancer. The objective RR was 34.3% (95% CI, 28.3 to 40.8%). Median progression-free survival was 4.1 months (95% CI, 2.4 - 4.9 months), and median overall survival was 23.5 months. More recently, a phase II randomized trial VOLFI trial: especially in patients with BRAF mutations, in terms of response rate: 71% versus 22% when compared with chemotherapy. However, there was no difference in median PFS (6.5 and 6.1 months).

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2020 消化系聯合學術演講年會

專題討論（六） Challenges in the Management of GERD in 2020 NOVEL APPROACHES TO THE EVALUATION OF GERD 陳健麟 花蓮慈濟醫院

Gastroesophageal reflux disease (GERD) is one of the most common diseases in current GI clinical practice. GERD has been defined as “a condition which occurs when gastric refluxates cause troublesome symptoms and/or complications.

Typical reflux symptoms include heartburn and acid regurgitation, whereas atypical symptoms of GERD include cough, chest pain, hoarseness, and wheezing or asthma symptoms. However, clinical history, questionnaire data and response to acid suppression therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are valuable in determining need for further investigation. Aside from upper endoscope, esophageal pH testing is recommended

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in patients with typical GERD symptoms who are refractory to a trial of proton pump inhibitors (PPIs) therapy, and those with atypical symptom which might origin from acid reflux or the symptoms despite PPIs therapy. Ambulatory esophageal reflux testing can be therefore performed by several different ways, including prolonged wireless sensors and impedancepH that allows detect reflux episodes by measuring acidic/non-acidic refluxates as well as symptom association. In this talk, novel parameters derived from impedance-pH will be also discussed together with biophysiological markers in order to obtain comprehensive evaluation of GERD.

2020 消化系聯合學術演講年會

專題討論（六） Challenges in the Management of GERD in 2020 EVALUATION AND MANAGEMENT OF PPI REFRACTORY GERD 曾屏輝 臺大醫院

Gastroesophageal reflux disease (GERD) has been associated with a broad spectrum of symptoms, and have a great impact on the quality of life of patients. The incidence and prevalence of GERD have increased remarkably over the past decades in Taiwan and worldwide, which is related to the epidemics of obesity and metabolic syndrome. Currently, proton pump inhibitor (PPI) remains the most potent antisecretory agent for acid suppression, symptomatic relief and mucosa healing, and is the drug of choice in the treatment of GERD. However, up to 40% of patients have poor responses to PPI. The reality of such a high proportion of GERD patients with the so-called “PPI failure” in clinical practice has been associated with frequent utilization of healthcare resource and therefore imposes a heavy financial burden in the medical economy. The underlying pathophysiology involved in refractory GERD is complex. Prior studies have reported that poor drug compliance, improper dosing time, delayed gastric emptying, concomitant functional bowel disorder, psychological comorbidity, reduced PPI bioavailability, rapid PPI metabolism, and obesity might affect the treatment response to PPI. Identifying factors that might attribute to the poor treatment response of PPI in GERD is very important to improve the overall treatment responses.

Currently, endoscopy is the mainstay of diagnostic

tool for patients with reflux symptoms in Taiwan, but a great proportion of patients have no esophageal mucosa changes on examination, so call non-erosive reflux disease (NERD). Recently 24-h MII-pH monitoring has been found to be the most sensitive tool in diagnosing GERD. The MII-pH catheter combines impedance channels to conventional pH catheters and helps to establish the reflux-symptom association with symptoms index (SI) and symptom association probability (SAP), and therefore is very useful in clarifying the underlying mechanism of refractory GERD. Compared with conventional 24-h pH monitoring, combined use of impedance and pH monitoring enables a differential diagnosis of all reflux events into acidic (pH <4), weakly acidic (pH >4, <7) and non-acidic (pH>7) and helps to tailor further management. With the aid of 24-h MII-pH monitoring, traditional GERD patients, who are quite heterogeneous from a pathophysiological point of view, could be further categorized into 1. endoscopic positive; 2. true NERD (patients with an excess of acid reflux); 3.hypersensitive esophagus to acid reflux; 4.hypersensitive esophagus to non-acid reflux) and 5.functional heartburn. In an era of total reflux awareness, tailored medicine with the application of combined MII-pH testing for patients with refractory reflux symptoms to PPI may be anticipated.

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2020 消化系聯合學術演講年會

專題討論（六） Challenges in the Management of GERD in 2020 ENDOSCOPIC THERAPY FOR GERD: WHEN TO CONSIDER? 王彥博 臺北榮民總醫院

Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disease characterized by bothersome heartburn and reflux symptom.

Lifestyle medication, acid suppressing therapy such as proton pump inhibitor, H2 receptor antagonist or anti-acid are the mainstay of treatment. For patients who are intolerant to medications’ adverse events, with coexisting hiatal hernia or on chronic medication usage, laparoscopic fundoplication is also effective in long-term symptom relief. In recent 20 years, several endoscopic anti-reflux therapy were developed for management of GERD. They were developed to fill the gap between surgery and medical treatment, complementary to both treatments and overcoming the shortcoming of both treatments. There are mainly two types of anti-reflux endoscopic therapy: (1) Lower esophageal sphincter(LES) augmentation, such as adiofrequency ablation (Stretta) and LINX reflux management system (2) Gastroesophageal

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junction(GEJ) reconstruction, including transoral incisionless fundoplication (TIF) mucosal ablation, suturing of GEJ, resection and plication procedure, full thickness plication, and Medligus ultrasonic surgical endostapler procedure(MUSE). Patients should receive a systemic review of their symptoms including symptom characteristics, lifestyle, comorbidities, and medications history. Ambulatory esophageal pH monitoring is mandatory for definite diagnosis of GERD. Esophagogastroduodenoscopy can help evaluation the severity of reflux esophagitis and structure of gastroesophageal junction. High resolution manometry can be used to exclude major esophageal motility disorders. Shared decision making with patients considering anti-reflux endoscopic treatment by discussion of esophageal function evaluation may improve the overall clinical outcome and avoid unnecessary treatment.

2020 消化系聯合學術演講年會

專題討論（七） Unmet Needs of Current Chronic Hepatitis B Treatment in Taiwan THE IMPACT OF PEGYLATED INTERFERON OR NUC TREATMENT ON RISK OF HCC IN CHB PATIENTS 楊宏志 臺大醫院

Despite the advance of current antiviral therapy, chronic hepatitis B (CHB) remains a challenging public health issue worldwide. A significant portion of patients with chronic HBV infection suffer from long-term adverse outcomes, including cirrhosis and hepatocellular carcinoma (HCC), so they require timely diagnosis and antiviral treatment. Current antiviral treatments for CHB, including pegylated interferon (IFN) and nucleos(t)ide analogues (NAs), suppress HBV through different mechanisms.

Interferon acts through direct antiviral inhibition and indirect immunomodulation, whereas NAs inhibits viral polymerase directly. Antiviral treatment has been shown to dramatically reduce the morbidity and mortality of CHB patients, including the decrease HCC risk. The impact of IFN-based therapy on HCC, compared to untreated CHB patients, has been clearly demonstrated in prior studies. Recently, NAs have also been shown to exhibit favorable effects on the development of HCC, particularly in patients with advanced fibrosis and cirrhosis. NAs with high genetic

barrier, like entecavir or tenofovir, seem to have more optimal effects against HCC. Although both IFN and NAs have demonstrated the promising effects on the reduction of HCC, they cannot entirely eliminate its risk. Patients under sustained virological control with NAs or those who even undergo HBsAg loss or seroconversion are still susceptible to the development of HCC. The risk of HCC is significantly higher in patients with certain risk factors, namely, male gender, high HBV DNA, high HBsAg, certain viral mutations, and advanced fibrosis or cirrhosis. Patients at high risk require closely monitor and surveillance for early diagnosis and treatment. Regarding this, several risk scores of HCC have been developed to help timely identify those at risk. In this talk, we will discuss the impact of pegylated IFN and NAs on the risk of HCC, and the potential mechanisms for HCC development under effective antiviral treatment. Additionally, we will also introduce several predicting models of HCC for effective surveillance of patients at risk in order to improve the patient care.

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2020 消化系聯合學術演講年會

專題討論（七） Unmet Needs of Current Chronic Hepatitis B Treatment in Taiwan THE TIMING OF RETREATMENT AFTER STOPPING NUC IN HBEAG-NEGATIVE CHB 鄭文睿 林口長庚紀念醫院

Finite Nuc therapy in HBeAg negative patients has been proved practicable and feasible in both Asian and Western studies recently. Increased HBsAg seroclearance rate (~13% by 6 years follow-up, annual incidence: 1.78%) was observed in those off-Nuc comparing to the continued treatment arm (annual incidence 0.15%) in cohort study and propensity-score matched studies. However, around half of the off-Nuc patients encounter issue of clinical relapse. Timing of retreatment has raised public attention since too

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early retreatment may lose the chance for spontaneous remission and later HBsAg seroclearance. However, risk of severe flare and hepatic decompensation also warrant attention and may be prevented if timely retreatment. The combine use of HBsAg, ALT during hepatitis flare (> 5X ULN) during clinical relapse may help the physician to differentiate effective and ineffective flare for further retreatment decision making.

2020 消化系聯合學術演講年會

專題討論（七） Unmet Needs of Current Chronic Hepatitis B Treatment in Taiwan BIOMARKERS IN THE MANAGEMENT OF CHB, BEYOND HBSAG 曾岱宗 臺大醫院

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 HBsAg positive. These individuals with chronic hepatitis B infection are at an increased risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). The current treatment of nucleos(t) ide analogues (NA)s ensure sustained virological suppression that will lead to biochemical remission, histological improvement, and prevention of complications. However, the most challenge in the management of hepatitis B is that there is still no HBV cure.

With recent advances in molecular biomarkers, more major issues could be addressed, including accurate prediction of HCC risks of untreated and NAtreated patients, patients who may stop NA therapy safely, and risk factors to predict HBV reactivation.

Serum HBV DNA and HBsAg levels are two well-known viral markers to provide us clinical guidance. Quantification of hepatitis B core-related

antigen (HBcrAg) and antibody against hepatitis core antigen (Anti-HBc) are another two emerging biomarkers, which may complement current prediction algorithms to address some of the important issues.

Serum HBV RNA level is another biomarker, which may persist even after HBV DNA is fully suppressed and may guide us who should not stop NA therapy. In addition to these viral biomarkers, 2 serum biomarkers indicative of liver fibrosis severity, including fibrosis-4 index (FIB-4) and Mac-2 binding protein glycan isomer (M2BPGi), are useful in predicting HCC development, especially in patients receiving prolonged NA therapy.

With more and more biomarkers available, we need to explore their role in clinical practice more comprehensively and validate these findings in independent study groups. The validated data will help us to design different treatment strategies and pave the way for the individualized management of patients with chronic HBV infection.

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2020 消化系聯合學術演講年會

專題討論（八） Factors Predicting Outcome in IBD PREDICTORS OF AGGRESSIVE UC 李柏賢 林口長庚紀念醫院

According to the registered database compiled by the National Health Insurance, the prevalence of ulcerative colitis was more than six times higher in 2015 than in 2001. Incidence of colectomy decreased after introduction of biologics. Therefore, it’s crucial to identify the patients who are likely to have a rapid and severe course of disease and then require more aggressive treatment to prevent colectomy. The predictors of an aggressive disease course include

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age <4o y/o at diagnosis, extensive colitis, severe endoscopic disease (Mayo endoscopic subsore 3, UCEIS≥7), hospitalization for colitis, elevated CRP and low serum albumin. As far as acute severe ulcerative colitis is concerned, low albumin, CRP/ albumin ratio >0.85, severe endoscopic lesions (deep ulcers, extensive loss of mucosal layers, well-like ulcers or large erosions) and higher UCEIS lead to higher colectomy rate.

2020 消化系聯合學術演講年會

專題討論（八） Factors Predicting Outcome in IBD PREDICTORS OF AGGRESSIVE CROHN’S DISEASES 章振旺 馬偕紀念醫院

Crohn’s disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), are causes of chronic gastrointestinal disease in the developed world. The exact cause of IBD remains unknown, but it is believed to be due to genetic, immune, and environmental factors. CD is a disease with chronic inflammation of unknown etiology involving any part of the gastrointestinal tract.

The incidence and prevalence of CD are increasing recently in Asia. Half of the CD patients will have intestinal complications, such as strictures or fistulas, within 20 years after diagnosis. Twentyfive percentage of CD patients have had at least one small bowel stricture and 10% have had at least one colonic stricture and lead to significant complications.

The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting

which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies.

There is no actual definition of aggressive CD. In general, aggressive CD can be defined as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. As with diagnosis of CD, no single method can predict disease aggressiveness.

Predictors of aggressive CD should be including clinical manifestations, endoscopic findings, multiple serologic and genetic tests. At present, the involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene, were the predictors in aggressive CD.

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2020 消化系聯合學術演講年會

專題討論（八） Factors Predicting Outcome in IBD PREDICTORS OF TREATMENT OUTCOMES FOR UC 鍾承軒 亞東紀念醫院

Mesalazine and steroids are mainstay management for mild ulcerative colitis (UC).

However, conventional therapies are less efficient for moderate to severe UC as compared with biological therapy. Among several treatment options, primary non-response or secondary loss of response

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sometimes develop to UC patients. Therefore, to identify predictors of benefit from specific agents is of paramount importance to help best position UC therapies. Herein, I will review the demographic, biochemical and genetic predictors of treatment outcomes in UC patients.

2020 消化系聯合學術演講年會

專題討論（八） Factors Predicting Outcome in IBD PREDICTORS OF TREATMENT OUTCOMES FOR CROHN’S DISEASE 李熹昌 臺北市立聯合醫院仁愛院區

The natural course of Crohn’s disease (CD) can range from an indolent course to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. Biomarkers, radiology findings, and endoscopic studies, together with clinical assessment of patients with CD, can be used to help determine prognosis, assess disease activity,

and increasingly to inform treatment decision-making.

Earlier treatment is associated with better clinical remission outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (ex, C-reactive protein, fecal calprotectin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management.

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2020 消化系聯合學術演講年會

專題討論（九） Update of Pancreatobiliary Endoscopy EUS-GUIDED BILIARY DRAINAGE 郭雨庭 臺大醫院

Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method for gaining biliary access, and managing both benign and malignant biliary obstructions. However, biliary cannulation can fail in 4% to 16% of ERCPs. Failure can occur owing to altered anatomy, periampullary diverticulum, ampullary pathology, tumor infiltration of the papilla, or gastric outlet obstruction. When ERCP fails, other options include surgical drainage, percutaneous transhepatic drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD).

EUS-BD has emerged as a safe and effective means of biliary decompression following failed ERCP. Although it is a complicated procedure requiring skilled endoscopists, it has several demonstrated advantages over surgical biliary drainage and PTBD. A recent review found that EUSBD was associated with better clinical success, fewer adverse events, and a lower rate of reintervention

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than PTBD. In the majority of these studies, EUS-BD was used as rescue procedure when ERCP has failed.

Recently, EUS-BD and ERCP have been compared in randomized, controlled studies for primary biliary drainage for malignant obstruction. All studies showed no significant difference in rates of technical or therapeutic success, or rate of adverse effects. EUSBD may be a safe and effective alternative to ERCP as a primary means of malignant biliary decompression, but further studies are warranted.

Although EUS-BD is an effective, safe, and innovative technique for biliary drainage when conventional ERCP fails, it is a complicated procedure that requires careful patient selection, highly skilled endoscopists, and has a learning curve. The accepted indications for EUS-BD are failed ERCP, altered anatomy, tumor preventing access into the biliary tree, and contraindication to percutaneous access such as large ascites.

2020 消化系聯合學術演講年會

專題討論（九） Update of Pancreatobiliary Endoscopy ENDOSCOPIC RFA FOR MALIGNANT BILIARY STRICTURE 李懿宬 臺北榮民總醫院

Malignant biliary stricture is associated with significant morbidity and mortality, which often presents with poor biliary drainage from tumor obstruction. The mainstay of the palliative management of unresectable malignant biliary stricture is biliary decompression, usually by endoscopic placement of self-expanding metal stents to prevent biliary obstruction and cholangitis. Adjuvant therapies such as chemotherapy and radiotherapy have failed to yield satisfactory results. Endoscopic radiofrequency

ablation (RFA) of the bile duct is an emerging modality for the local treatment of malignant biliary stricture. Potential indications for biliary RFA include palliative treatment of malignant biliary strictures, avoiding stent occlusion, ablating ingrowth of blocked metal stents, prolonging stent patency, and ablating residual tumor tissue after endoscopic ampullectomy.

In this topic, we will review the advances in the endoscopic RFA techniques in the management of malignant biliary stricture.

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2020 消化系聯合學術演講年會

專題討論（九） Update of Pancreatobiliary Endoscopy UPDATES IN THE ENDOSCOPIC MANAGEMENT OF BENIGN AND MALIGNANT BILIARY OBSTRUCTION 劉乃仁 林口長庚紀念醫院

Therapeutic endoscopic retrograde cholangiography and pancreatography (ERCP) is the first-line management option for bile duct strictures.

Stricture dilation and multiple plastic stents placement are effective in the treatment of benign biliary stricture (BBS). Tubular fully covered metal stents are at risk of stent migration which may reduce the treatment efficacy and increase risk of adverse events in the treatment of BBS. Evolution of stent design with modified nonflared short fully covered metal stent which is placed just at the stricture is promising in most etiology of BBS. Biliary metal stent placement is the standard treatment of palliative malignant distal bile duct stricture. Palliative treatment of malignant perihilar obstruction is more technically demanding.

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Metal stents designed for bilateral intrahepatic duct placement with sequential, simultaneous side-by-side or stent-in-stent fashions are available on the market.

Adjuvant treatment with endobiliary radiofrequency ablation is also a promising therapy in patient with unresectable malignant biliary obstruction. The procedure is safe, well tolerated and improves stent patency and survival.

With the advent of interventional endoscopic ultrasound, various EUS-guided biliary interventions have been developed for patients in whom ERCP is difficult to carry out. Although interventional EUS is a useful therapeutic procedure, there are still no dedicated devices, and standardization of the procedure is warranted.

2020 消化系聯合學術演講年會

專題討論（九） Update of Pancreatobiliary Endoscopy ENDOSCOPIC DIAGNOSIS AND TREATMENT OF AUTOIMMUNE BILIARY DISEASE (PRIMARY BILIARY CIRRHOSIS, PRIMARY SCLEROSING CHOLANGITIS, AND IMMUNOGLOBULIN G4-RELATED HEPATOBILIARY DISEASE) 陳建華 臺北慈濟醫院

Primary biliary cholangitis (cirrhosis)-PBC is a chronic cholestatic disease with female predominance.

It is characterized by inflammation of the bile ducts and can eventually progress to cirrhosis. Most patients remain asymptomatic and are diagnosed by the casual finding of an anicteric biochemical cholestasis with increased alkaline phosphatase and gammaGlutamyltransferase. The pathogenesis is unknown and of presumed autoimmune origin in genetic susceptible subjects. M2-type anti-mitochondrial antibodies, and specific antinuclear antibodies are typical and specific of the disease. The positivity of these antibodies and a biochemical cholestasis are sufficient for diagnosis, without the need for liver biopsy. Ursodeoxycholic acid is the specific treatment with an excellent response. Endoscopic treatment is no role for patients with PBC. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by intrahepatic or extrahepatic stricture, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. The key diagnostic features are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play an importantly

pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease, who require colonoscopic screening and surveillance.

PSC is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection is of vital importance. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.

Immunoglobulin G4 (IgG4)-related hepatobiliary disease (IgG4-RHBD) is a novel clinicopathological disease entity. It was formerly recognized as one of extra-pancreatic diseases of autoimmune pancreatitis.

Now, it is considered as one of the IgG4- related sclerosing diseases, which are characterized by high serum IgG4 concentrations and extensive infiltration of IgG4-positive plasma cells into the involved organs.

The hallmarks of IgG4-RD are lymphoplasmacytic tissue infiltration with a predominance of IgG4positive plasma cells and CD4 (+) T lymphocytes, usually accompanied by fibrosis, obliterative phlebitis, and elevated serum levels of IgG4.

Modern imaging modalities have led to significant improvements in the localization and accurate diagnosis of biliary diseases. Tissue acquisition for pathological diagnosis is important to disease treatment. Endoscopic retrograde

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2020 消化系聯合學術演講年會

cholangiopancreatography (ERCP) is the goldstandard investigation tool for bilio-pancreatic disease. Peroral cholangiography (POCS) is a useful modality not only for diagnosing biliary disease, but for therapeutic procedures as well. Currently available types of peroral cholangioscopy include peroral video cholangioscopy using a mother-baby scope system (MBSS), direct peroral video cholangioscopy (D-POCS), and SpyGlass ™ Direct System (SPYDS). In the early twenty first century, POCS started with cholangioscopy using MBSS, requiring two doctors using two scopes. On the other hand, D-POCS and SPYDS were developed as single-operator techniques. The MBSS enables comparatively easy scope insertion into the bile duct and provides

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excellent images and can be coupled with an imageenhanced function system. However, scope fragility is serious problem. D-POCS using an ultrathin upper endoscope has a larger working channel and requires only one endoscopist; however, scope insertion is still challenging. The SPY-DS single-operator cholangioscope offers favorable visualization, a wide view, suction function and a larger accessory working channel. When used in the evaluation of indeterminate biliary strictures by experienced endoscopists in recognizing intraductal pathology, it increases the diagnostic yield of tissue sampling. Nevertheless, if the duodenoscope cannot be advanced into the ampulla of Vater for reasons such as surgical anatomy, POCS cannot be performed.

2020 消化系聯合學術演講年會

專題討論（九） Update of Pancreatobiliary Endoscopy ADVANCES IN CHOLANGIOSCOPY, CONFOCAL ENDOMICROSCOPY AND OPTICAL COHERENCE TOMOGRAPHY 邱逸群 高雄長庚紀念醫院

In recent years, several new developments in the field of gastrointestinal endoscopy, such as cholangioscopy, confocal endomicroscopy and optical coherence tomography. New disposable cholangioscopy, but acceptable price, have been developed that permit direct visualization of the bile and pancreatic ducts. Confocal laser endomicroscopy is endoscopic technologies that permit high-resolution assessment of gastrointestinal mucosal histology at a cellular and sub-cellular level.

Optical coherence tomography (OCT) is an emerging medical imaging technology that relies on

the backscattering of light to obtain cross-sectional images of tissue. There have been several pilot studies using OCT in the gastrointestinal tract. These have demonstrated the feasibility of this technology to enhance endoscopic imaging of the superficial layers of the esophagus, stomach, bile ducts, pancreatic duct, and colon.

This lecture will review recent advance in cholangioscopy, confocal endomicroscopy and optical coherence tomography, including the technical aspects of the procedures, their indications, and efficacies.

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2020 消化系聯合學術演講年會

專題討論（十） Pancreatic Cancer Progression: Novel Molecular Mechanisms and Translational Opportunities BARCODED NANOPARTICLES FOR PRECISION CANCER MEDICINE: TARGETING PANCREATIC TUMORS WITH NANOTECHNOLOGY Avi Schroeder Associate Professor of Chemical Engineering, Technion; Adjunct Associate Professor of Biomedical Engineering, Technion - Israel Institute of Technology

Medicine is taking its first steps towards patientspecific cancer care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes including siRNA and protein, as well as targeting to specific cell populations.

The talk will discuss ‘barcoded nanoparticles’ that target sites of cancer where they perform a programmed therapeutic task. Specifically, liposomes that diagnose the tumor and metastasis for their sensitivity to different medications, providing patientspecific drug activity information that can be used to improve the medication choice.

The talk will also describe how the liposomal lipid composition can be used as multi-functional systems for degrading the pancreatic stroma to allow subsequent drug penetration into pancreatic adenocarcinoma, and how the nanoparticle configuration can be leveraged to induce an anti-tumor immune response.

The evolution of drug delivery systems into synthetic cells, programmed nanoparticles that have an autonomous capacity to synthesize diagnostic and therapeutic proteins inside the body, and their promise for treating cancer and immunotherapy, will be discussed.

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References: 1) T h e r a n o s t i c b a r c o d e d n a n o p a r t i c l e s f o r personalized cancer medicine, Yaari et al. Nature Communications, 2016, 7, 13325 2) Synthetic Cells Synthesize Therapeutic Proteins i n s i d e Tu m o r s , K r i n s k y e t a l . , A d v a n c e d Healthcare Materials, 2017 3) Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors, Zinger et al., ACS Nano, 2019

2020 消化系聯合學術演講年會

專題討論（十） Pancreatic Cancer Progression: Novel Molecular Mechanisms and Translational Opportunities THE ROLE OF OPN IN PANCREATIC CANCER 沈延盛 國立成功大學醫學院臨床醫學研究所

Despite massive research efforts in past decades, pancreatic cancer (PC) remains one of the deadliest malignancies, with a 5-year survival rate less than 10%. Several important factors are involved in the high mortality rate of PC, including its characteristics of clinical silence in early stages, high incidence of local invasion and distant metastasis, resistance to radiotherapy and most systemic chemotherapies.

Surgery is one of the most effective therapeutic strategies; unfortunately, 80-85% of patients present with advanced unresectable status. Gemcitabinebased systemic chemotherapy is the mainstay of treatment in patients with unresectable PC; however, the prognosis is still poor. Osteopontin (OPN), a secreted glycoprotein, overexpresses in many types of cancer and has been reported in association with chemoresistance. Our previous studies showed OPN/ NF-κB-mediated autophagy is required for pancreatic cancer stem cells (CSCs) maintenance. Blockade of autophagy suppresses tumor formation and sensitize pancreatic CSCs to gemcitabine (GEM). We also observed that plasma OPN levels had significant

decreased in PC patients response to GEM-based chemotherapy, while increased in patients with progression after GEM-based chemotherapy. OPN expression was elevated in PC cell lines with GEM treatment or GEM-resistant PC cell lines. Therefore, we explore the mechanism of OPN in promoting chemoresistance. We find that OPN can mediate autophagy through AMPK-ULK1-ATG5 axis to increase ATP production and thus contribute to activity of ABC transporters, which are often responsible for enhancing drug resistance by medicating drug efflux.

We also investigate the underlying mechanisms of OPN secreted by cancer cells. We find that Rab37, a member of the Ras superfamily of GTPases that controls cargo protein trafficking, can regulate OPN secretion and involve in promoting cancer metastasis and stemness. These findings highlight the important role of OPN in pancreatic cancer metastasis, stemness, and chemoresistance and offer the potential for prognosis evaluation of PC and help in designing promising therapeutic strategies.

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2020 消化系聯合學術演講年會

專題討論（十） Pancreatic Cancer Progression: Novel Molecular Mechanisms and Translational Opportunities STK24 INDUCES PANCREATIC DUCTAL ADENOCARCINOMA PROLIFERATION AND CHEMORESISTANCE BY MODULATING AUTOPHAGY 鄭光宏 國立中山大學生物醫學研究所

Pancreatic ductal adenocarcinoma (PDAC) is the most deadly of human adult malignancies with notable resistance to chemotherapy, and was characterized by the mutations of KRAS (90%), INK4a (85%), p53 (50%) and TGFβ1/SMAD4 (45%).

Recently, the induction of autophagy in response to metabolic and therapeutic stresses is now emerging as a crucial factor contributing to the anticancer efficacy of chemotherapy as well as drug resistance.

STK24 also named MST3, a mammalian STE20like serine/ threonine protein kinases family member, is known to induce cell growth and promote tumor development. However, the potential roles of STK24 in PDAC development to be determined. To study the pathological roles of STK24 in PDAC, this study rests on the hypothesis that the mouse can serve as a genetic model system to a) understand how the STK24 expression status governs specific biological processes in the pathological progression of PDAC,

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b) determine the cooperative interactions for example, Kras activation and the upregulation of STK24 in a defined in vivo setting, and c) validate the role of STK24 oncogene and STK24-AMPK-ULK1 - induced autophagic signaling surrogates in tumor maintenance.

Specifically, we hypothesize that activated Kras and STK24 overexpression play specific and cooperative roles in the pathogenesis and progression of pancreatic ductal neoplasia. Loss of STK24 in PDAC is likely to inhibit the autophagy and cell proliferation during Kras driven pancreatic intra-neoplastic lesions (PanINs) formation, and may lead to the increase of apoptosis during PDAC development. Thus, the identification of STK24-induced autophagy signaling components that are essential for tumorigenic growth of PDAC will subsequently be used in the design of preclinical trials that employ therapeutics to target PDAC.

2020 消化系聯合學術演講年會

專題討論（十） Pancreatic Cancer Progression: Novel Molecular Mechanisms and Translational Opportunities NOVEL DRIVERS OF PANCREATIC CANCER STEMNESS AND AGGRESSIVENESS 蔡坤志 臺北醫學大學臨床醫學研究所、萬芳醫院、國家衛生研究院癌症研究所

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-resistant malignancy and the third leading cause of cancer-related death.

Despite recent advances in nanoparticle-formulated chemotherapy and immuno-therapy, only a small fraction of patients with PDAC respond to these new types of therapies and the survival benefit gained from them is very limited. Stem-cell-like cancer cells or cancer stem cells (CSCs) have been considered as the driving force of PDAC aggressiveness and metastasis.

However, therapeutics aiming at inhibiting or killing CSCs have suffered from a series of setbacks in clinical trials, which trigger efforts to refine the

current CSC model and exploit alternative therapeutic strategies. We thus envisage that simply characterizing CSCs using surrogate markers will not lead to further improvements in CSC-targeted therapies without elucidating the underlying molecular mechanisms driving tumor stemness. I here will introduce several recently identified molecular drivers of cancer stemness in PDAC, including HNF1A, Musashi, ROR-γ, and ASPMiI. I summarize our recent works in the novel Wnt co-regulator ASPMiI, emphasizing its pathogenetic role in PDAC aggressiveness and its translational potential as a novel prognostic marker and therapeutic target in PDAC.

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2020 消化系聯合學術演講年會

一般演講

主題：C 型肝炎（一）

①

慢性 C 型肝炎病人接受口服抗病毒藥物治 療失敗原因探討：抗藥基因之分析 CAUSES OF DAA TREATMENT FAILURE OF CHRONIC HEPATITIS C: ANALYSIS OF RESISTANCE ASSOCIATED SUBSTITUTION 1

2,3

3

4

2

2,3

洪俊銘 劉俊人 林友瑜 葉秀慧 楊宏志 高嘉宏 10 2,5 9 2,6 5 2,7 楊勝舜 陳健弘 黃怡翔 黃冠棠 徐士哲 楊培銘 2,7 8 2,3 許金川 余明隆 陳培哲 1 臺大醫院內科部整合醫學科 2 臺大醫院內科部肝膽腸胃科 3 臺灣大學醫學院臨床醫學研究所 4 臺灣大學醫學院微生物所 5 臺大醫院雲林分院內科 6 中國醫藥大學內科部 7 好心肝基金會 8 高雄醫學大學附設醫院內科 9 臺北榮民總醫院內科部肝膽腸胃科 10 臺中榮民總醫院內科部肝膽腸胃科 Background: Chronic hepatitis C (CHC) is common in Taiwan, as about 4% of population are positive for anti-HCV Ab. Among them, around 70% carry HCV RNA, therefore about 500,000 cases are CHC patients.

The Bureau of National Health Insurance has started to reimburse DAAs (direct-acting antiviral agents) since 2017.

Preliminary data from Hepatitis C Flagship Project Office showed an HCV cure rate of 97%, meaning that there are still 2-3% of patients who fail to clear HCV despite completing the treatment. In order to understand the causes of treatment failure in Taiwan, it is essential to conduct a clinical and virologic study of these DAA failure patients.

Aims: To investigate causes of DAA treatment failure from clinical and virology aspects.

Methods: Through collaboration with several hospitals and clinics nationwide, we recruited 40 DAA failure patients. These patients received at least four-week treatment of DAA therapy. Clinical information as well as serum samples were obtained after informed consent. We established polymerase chain reaction (PCR) platform for NS3/4A, NS5A and NS5B, and then identified mutated RAS (resistance-associated substitution) by population sequencing.

Results: In these 40 patients, only one patient did not complete treatment due to hyperbilirubinemia. Sixteen patients had genotype 1b infection, twelve had genotype 2, and two had genotype 3.

52

Till now, we completed RAS (resistance associated substitution) analysis for 21 patients among these 40 patients. Eight cases were found to have no known RAS according to its genotype and DAA regimen, and the rest 13 cases were found to have at least one mutated RAS. Y93 in NS5A was the most RAS, and its frequency of mutation (91%) was significantly higher than that in HCV database (14%). The frequency of mutation of Y56 in NS3 and L31 in NS5A were also higher than those in HCV database. On the other hand, the frequency of mutation of D168 in NS3 and L159 as well as C316 in NS5B were not higher than those in HCV database. Furthermore, two cases were noted with post-DAA HCV genotypes that were different from the baseline genotypes, suggesting initial mixed infections or a reinfection.

Conclusions: Our study suggests that known RASs are the major virologic cause for treatment failure. Those without known RASs warrant further investigation in order to propose appropriate rescue therapies.

2020 消化系聯合學術演講年會

②

直接作用抗病毒藥物 (DAAs) 對於因注射毒 品而感染 C 型肝炎之特殊族群患者於台南 監獄之治療經驗與成效 THE EFFICACY OF DIRECT-ACTING ANTIVIRAL AGENTS (DAAS) TREATMENT FOR INJECTING DRUG USERS WITH HEPATITIS C IN TAINAN PRISON, AGENCY OF CORRECTION – INITIAL EXPERIENCE OF HCV MICROELIMINATION IN PWID 毛元治 牟聯瑞 臺南市立醫院（委託秀傳醫療社團法人經營） Background: People who inject drugs (PWID) are quite likely to get hepatitis C through the blood transmission.

According to the previous studies, the rate of hepatitis C infection among injecting drug users is about 60-80%. In Western countries, PWID is a special group of chronic HCV infection because these patient group are not easy to find and follow-up. It is also difficult to study or treat in these patients’ group because of poor compliance of drug adherence and follow-up. In Taiwan, prisons have held a considerable number of PWID and they are also incarcerated in prison for a significant time period. Under such circumstances, the screening, treatment and follow-up of this group become easy. These characteristics made the micro-elimination of PWID in prison possible.

Aims: To study the HCV infection of PWID in Tainan prison, its genotyping, viral load and treatment efficacy with DAAs in this special patient group.

Methods: An outreach patient clinic was setup in Tainan Prison by Tainan Municipal Hospital since 2013.

Since mass screening is not performed in PWID due to noncooperation of prison, anti-HCV detection was made only if the patient is a PWIDS by history taking during his visit. Viral load, genotype, HBsAg and other blood test were all done in all anti-HCV+ PWID patient according to the regulation of National health Insurance (NHI). The patient received DAAs treatment according to the different situation such as genotyping, viral load and liver fibrosis status. HCV RNA was checked at 2 time point to confirm the viral response (VR) after treatment of DAAs including end of treatment (EOTVR) and 12 weeks after ceasing treatment (SVR12). Abdominal ultrasound examination was performed before DAAs treatment and 12 weeks after ceasing treatment.

Results: From Jan. 2019 to Jul. 2019, a total of 151 HCV

patients of PWID received DAAs treatment and completed six months of follow-up in Tainan Prison. All patients are male in gender,and are mostly 40~60 years old. The HCV genotype was 1a/1b/2/3/6/mixed (29/16.5/12.5/10/29/2.6%) respectively. 69 patients (45.6%) belonged to the medium viral load (0.8-6 million IU/ml), 31 patients (20.5%) had high viral load (>6 million IU/ml) and the other 51 patients’ (33.9%) viral load less than 0.8 million IU/ml. No patients discontinued DAAs due to side effects. The DAAs used for treatment were Harvoni in 102 patients (67.5%), Maviret 41 patients (27.1%), Zepatier in 8 patients( 5.2%) respectively. 150 patients achieved EOTVR (99.3%) and all achieved SVR12 (100%). However, one patient with high viral load and mixed genotype developed HCV relapse presenting as elevated liver enzymes 5 weeks after SVR12.

The rechecked HCV RNA viral load showed 1,853,532IU/ mL. Analysis of this patient, it showed high viral load (HCV RNA:12,980,203IU/mL) before treatment, mixed genotype and received Maviret 8 weeks. The final SVR rate is 99.33% Conclusions: The treatment efficacy of PWID in prison is the same or even better than in general people, probably due to more drug adherence and compliance. Since mixed genotype HCV infection is higher in PWID, an extended treatment of DAA or add on Ribavirin may be considered for the possibility of genotype 3 infection.

From our initial experience in Tainan prison, this mode of micro-elimination may be applied to other prisons in Taiwan to facilitate the government’s policy, elimination of HCV infection by 2025.

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2020 消化系聯合學術演講年會

③

台灣慢性 C 型肝炎與慢性 B 型肝炎合併感 染之病人使用雷迪帕韋／索非布費治療後 108 周的追蹤 LEDIPASVIR/SOFOSBUVIR FOR PATIENTS COINFECTED WITH CHRONIC HEPATITIS C AND HEPATITIS B IN TAIWAN: FOLLOW-UP 108 WEEKS POSTTREATMENT 1

1,2,3

4

5

6

7

鍾睿翔 劉俊人 莊萬龍 沈一嫻 王鴻源 陳啟益 8 9 10 11 12 曾國枝 張定宗 Benedetta Massetto 胡琮輝 徐友春 13 14 15 16 17 1,3 羅錦河 朱啟仁 陳志州 彭成元 簡榮南 陳培哲 1 臺大醫院內科部胃腸肝膽科 2 臺大醫院肝炎研究中心 3 臺大醫院臨床醫學研究所 4 高雄醫學大學附設醫院 5 林口長庚醫院 6 臺北馬偕醫院 7 嘉義基督教醫院 8 大林慈濟醫院 9 成功大學醫學院附設醫院 10 吉利德科學公司 11 高雄長庚醫院 12 彰化基督教醫院 13 義大醫院 14 臺北榮民總醫院 15 奇美醫院 16 中國醫藥大學附設醫院 17 基隆長庚醫院 Background: In persons chronically coinfected with hepatitis C virus (HCV) and hepatitis B virus (HBV), HCV treatment with direct-acting antivirals can lead to reactivation of HBV. Aims: We evaluated the frequency and characteristics of HBV virologic and clinical reactivation during ledipasvir/ sofosbuvir treatment and 108-week follow-up.

Methods: In Taiwan, 111 patients chronically infected with HCV genotype 1 or 2 and HBV received ledipasvir 90 mg/ sofosbuvir 400 mg once daily for 12 weeks. HBV virologic reactivation was defined as postbaseline increase in HBV DNA from either < lower limit of quantification (LLOQ, 20 IU/mL) to ≥ LLOQ or ≥ LLOQ to > 1 log10 IU/mL. HBV clinical reactivation was defined as HBV virologic reactivation with alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN). Logistic regression analysis was used to evaluate factors associated with development of HBV virologic or clinical reactivation.

54

Results: All patients (100%, 108/108) maintained suppression of HCV through 108 weeks after treatment.

HBV virologic reactivation occurred in 73% of patients (81/111). Clinical reactivation occurred in 9% of participants (10/111). The majority of cases of HBV virologic reactivation (86%, 70/81) occurred by follow-up week 12. Clinical reactivation was generally more delayed, happening between weeks 12 and 48 of follow-up in 4 patients. Eight patients (7%, 8/111) initiated HBV therapy.

In univariate and multivariate analyses, no factors were associated with HBV virologic or clinical reactivation.

Conclusions: Among HCV/HBV coinfected patients treated with direct-acting antivirals for HCV, HBV virologic reactivation occurred in a majority of patients during treatment and follow-up. HBV virologic reactivation was asymptomatic; only a minority initiated HBV treatment. Notably, clinical reactivation is transient and may still occur >3 months after end of therapy.

2020 消化系聯合學術演講年會

④

慢性 C 型肝炎基因型 1b 併重度肝纖維化病 患使用 Daclatasvir plus asunaprevir 之療效 及安全性 DACLATASVIR PLUS ASUNAPREVIR IS HIGHLY EFFECTIVE FOR ADVANCED FIBROTIC GENOTYPE-1B CHRONIC HEPATITIS C INFECTION IN TAIWAN AFTER PRE-EXCLUDING NS5A RESISTANCE-ASSOCIATED VARIANTS 1

1

1

1

2

1

吳思賢 朱啟仁 蘇品碩 蘇建維 林崇棋 李發耀 1 1, 3 黃怡翔 侯明志 1 臺北榮民總醫院胃腸肝膽科 2 臺北榮民總醫院健康管理中心 3 臺北榮民總醫院內科部

respectively. Grades of adverse events were generally mild and all patients completed treatment without early withdrawal. After post-treatment follow-up, 81 patients (96.4%) achieved SVR12. Virological analyses showed one patient with treatment failure due to selection of NS3 RAV D168E, the other two patients had treatment failure caused by mixed genotypes 3 and 6 infection.

Conclusions: Our real-world cohort of Taiwan showed a 24-week DCV/ASV-based treatment was well-tolerated and highly effective for advanced fibrotic genotype-1b CHC in Taiwan after pre-excluding NS5A RAVs. Mixed genotypes infection and selection of NS3 RAV are the main causes responsible for treatment failure.

Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis, hepatic decompensation, hepatocellular carcinoma and liver transplantation candidacies. Treatment of chronic hepatitis C (CHC) evolved rapidly due to the invention of interferon-free direct antiviral agents (DAAs). Genotype 1 accounts for approximately 70% of all HCV infections and subgenotype 1b is most predominant in Europe and Eastern Asia, including Taiwan.

Aims: To investigate the efficacy and safety of daclatasvir (DCV) plus asunaprevir (ASV), the first all oral DAAs combination treatment in the East Asia for genotype 1b CHC, in real world setting of Taiwan.

Methods: Between October 2016 to December 2018, 84 consecutive genotype-1b CHC patients with advanced fibrosis (≥ F3) who completed 24 weeks combination of DCV (60mg/day) plus ASV (200mg/day) by investigators were enrolled for analyses. Patients who were DAAexperienced prior to screening or carried overt NS5A L31F/ I/M or Y93H resistance-associated variants (RAVs) were excluded. SVR12 was defined by undetectable HCV RNA (< 15 IU/mL) at the end and 12 weeks after completion of therapy.

Results: The mean age was 64.1±11.5 years, 30 (35.7%) of them were males and 36 (42.9%) of them failed to previous IFN. 21 (25.0%) patients was diagnosed as liver cirrhosis and 14 (16.7%) had end stage renal disease under hemodialysis. The mean baseline HCV RNA level was 6.03±0.96 log10 IU/mL and 46 (54.8%) had baseline HCV RNA ≥ 2 million IU/mL. The rates of undetectable HCV RNA (< 15 IU/mL) at week-2, week-4, week-12 and end-of-treatment were 67.9%, 92.9%, 97.6 and 97.6%

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2020 消化系聯合學術演講年會

⑤

慢性 C 型肝炎基因型第二型病患以直接作 用抗病毒藥物 (DAA) 治療完全的真實世界 的效果 REAL-WORLD EFFECTIVENESS OF DIRECT-ACTING ANTIVIRAL AGENTS (DAAS) FOR CHRONIC HEPATITIS C PATIENTS WITH GENOTYPE-2 INFECTION AFTER COMPLETED TREATMENT. 1

1

1,2

1,2

1,2

1

鄭自勝 梁博程 黃釧峰 葉明倫 黃駿逸 林子堯 1,2 1,2 1,2 1,2 1,2 陳信成 黃志富 戴嘉言 莊萬龍 余明隆 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學院醫學系

Background: Several direct acting antiviral agents (DAAs), including Sofosbuvir (SOF) plus different NS5A inhibitors, and a non-SOF-based DAAs including Glecaprevir/pibrentasvir (GLE/PIB), have been approved and reimbursed by National Health Insurance for treating chronic hepatitis C (CHC) genotype-2 patients in Taiwan.

Data of real-world effectiveness of these DAAs in genotype-2 CHC patients are still limited.

Aims: We aimed to evaluate the real-world sustaind virological response (SVR) of glecaprevir/pibrentasvir (GLE/PIB), and SOF-based DAAs regimens in CHC genotype 2 patients receiving completed courses of therapy.

Methods: This retrospective study enrolling CHC patients with genotype 2 infection treated with various SOFbased DAAs and GLE/PIB at single medical center in Kaohsiung City from December 2013 to July 2019. The treatment regimens including SOF+ribavirin (RBV), SOF/ daclatasvir (DCV)±RBV, SOF/ledipasvir (LDV), and SOF/ velpatasvir (VEL) for 12 weeks, and GLE/PIB for 8 or 12 weeks. All patients have received completed courses (planned duration) and with data of HCV viral load data at 12 weeks after completion of DAAs therapy (end of follow up; EOF). We excluded patients who with treatment discontinuation, loss of follow‐up, and who expired during or after treatment. The primary effectiveness endpoint was clearance of the HCV RNA at EOF (SVR12).

Results: Till 20 December, 2019, a total of 704 patients (male 37.8%, mean age 62.7±11.8 years) with HCV genotype 2 infection were enrolled. The patients were treated with SOF+RBV (n=229), SOF/DCV±RBV (n=123), SOF/LDV (n=140), and SOF/VEL (n=16) for 12 weeks, and GLE/PIB (n=196) for 8 (n=149) or 12 (n=47) weeks.

The overall SVR12 rate was 97.9%. The SVR12 rate was

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significantly lower in SOF+RBV group (95.6%) than groups of SOF/DCV±RBV (100%) (p=0.017) and GLE/ PIB (99.5%) (p=0.013), but similar to groups of SOF/ LDV (97.1%) (p= 0.461) and SOF/VEL (100%) (p=1.0).

SVR12 rates were similar in all other four DAA regimens.

In patients with advanced chronic kidney disease (CKD stage 4 or 5) (n=37) treated with GLE/PIB, SVR12 rates were similar to patients without advanced CKD (100 % vs.

97.8%, respectively, p=1.0).

Conclusions: In southern Taiwan, for HCV-2 patients with completed course of therapy, SVR12 rate is significantly lower in SOF+RBV regimen. SOF in combination with DCV± RBV, LDV, or VEL and GLE/PIB achieve similar high efficacy. Advanced CKD population treated with GLE/ PIB also has high SVR12 rate.

2020 消化系聯合學術演講年會

主題：B 型肝炎（一）

⑥

探討 C 型肝炎使用全口服抗病毒藥物病人 治療期間 ALT 持續上升之狀況 PERSISTENTLY ON-TREATMENT ALANINE AMINOTRANSFERASE ELEVATION (POAE) IN PATIENTS WITH CHRONIC HEPATITIS C RECEIVING INTERFERON (IFN)-FREE DIRECT ACTING ANTIVIRALS (DAAS) 1

1, 2

1, 2

1, 2

1

1, 2

邱毓澤 劉振驊 劉俊人 陳培哲 陳定信 高嘉宏 1 國立臺灣大學醫學院附設醫院消化內科 2 國立臺灣大學醫學院附設醫院肝炎研究中心

Background: Persistent on-treatment ALT elevation (POAE) tends to occur more frequently in patients with advanced hepatic fibrosis and steatosis, and is associated with treatment failure by interferon (IFN)-based therapies.

However, data are limited with regard to the clinical implications for patients receiving IFN-free direct acting antivirals (DAAs).

Aims: To investigate the prevalence, risk factors and clinical implications of POAE in patients receiving DAAs Methods: A total of 395 patients receiving DAAs were retrospectively recruited. Data about the baseline patient characteristics, on-treatment ALT and HCV RNA levels, as well as the off-therapy week 12 treatment responses (SVR12) were collected for all patients. POAE was defined as persistently ALT quotients ≥ 1.5 for more than 4 weeks after the first presence of serum undetectable HCV RNA levels. The prevalence, risk factors with POAE, and its effect on SVR12 were assessed.

Results: Of the 395 cases, 25 (6.3%) had met the criteria for POAE. Multivariate analysis showed that patients with baseline ALT quotient ≥ 3 (odds ratio [OR]: 3.6, p = 0.009) and hepatic fibrosis ≥ F2 (OR: 4.1, p = 0.028) were associated with the presence of POAE. In contrary to patients under interferon, patients receiving DAAs who presented with POAE all achieved SVR12 in the end, and hence POAE isn’t associated with the SVR rate for DAAs. Conclusions: Pre-existing pathogenic condition of liver, including a higher baseline ALT level and a more advanced fibrosis stage, predisposes patients receiving DAAs to POAE. Different from patients under interferon, those receiving DAAs had less events of POAE, and POAE is not associated with SVR rate for DAAs.

⑦

先發性抗病毒藥物治療可防止肝癌病患在 接受免疫治療期間發生 B 型肝炎病毒再活 化 NO RISK OF HEPATITIS B REACTIVATION IN HEPATOCELLULAR CARCINOMA PATIENTS WITH HBV DNA ≥100 IU/ML UNDERGOING IMMUNE CHECKPOINT INHIBITOR IMMUNOTHERAPY BY PRE-EMPTIVE ANTIVIRAL STRATEGY 1

2

1

1

1

李沛璋 趙毅 李杰如 侯明志 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 臺北榮民總醫院腫瘤醫學部

Background: Immunotherapy with checkpoint inhibitor (ICI) is a promising and FDA-approved treatment for unresectable hepatocellular carcinoma (HCC). According to the clinical trials (CheckMate-040 and Keynote-224), effective anti-viral treatment and lower HBV viral load (<100 IU/mL) was required in patients with chronic hepatitis B before entering to ICI treatment. However, the rationale was still unclear Aims: To investigate the effect of anti-viral treatment on the status of hepatitis in patients with unresectable HCC during immunotherapy.

Methods: From May 2017, 66 patients had received treatment of ICI (nivolumab or pembrolizumab) for unresectable HBV related HCC in Taipei Veterans General Hospital. Among them, 62 patients with documented baseline serum HBV-DNA level were enrolled for clinical assessment. HBV reactivation is defined as a 10-fold increase in HBV viral load.

Results: At the date of data cut on November 15, 2019, the objective response rate was 27.8%, including 2 (3.7%) complete responses and 13 (24.1%) partial responses. The median time to response was 61 days (IQR 46–75 days), and the median duration of response was 5.8 months (IQR 2.9–10.0) for responders. Patients received nucleos(t)ide analogues (NUCs) (n = 55) had similar objective response rate (ORR) to those without NUCs treatment (n = 7) (ORR: 27.1% vs. 33.3%, p = 1.000). HBV reactivation developed in one patient (14.3%) who did not receive NUCs treatment during immunotherapy; whereas, no such event developed in patients with NUCs treatment. Among 23 patients with HBV viral load ≥100 IU/mL at the time of immunotherapy, 19 patients received pre-emptive NUCs treatment and 4 patients did not have NUCs treatment. All

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2020 消化系聯合學術演講年會

patients administrated with NUCs were safe from viral reactivation; whereas, one patient (25.0%) without NUCs treatment experienced HBV reactivation. The other patients with HBV viral load less than 100 IU/mL at the time of immunotherapy were free from HBV reactivation during immunotherapy regardless of NUCs treatment or not.

Conclusions: ICI treatment is not contraindicated for HCC patients with HBV viral load higher than 100 IU/mL once pre-emptive NUCs could be provided.

⑧

B 型肝炎基因型在 E 抗原陰性慢性 B 型肝 炎病人停止貝樂克或惠立妥後再復發所扮 演的角色 THE ROLE OF HBV GENOTYPES IN HBV RELAPSE AFTER CESSATION OF ENTECAVIR OR TENOFOVIR IN HBEAG-NEGATIVE PATIENTS WITHOUT CIRRHOSIS 1

1

1

2

1

2

邱紹銘 陳建宏 王景弘 洪肇宏 胡琮輝 盧勝男 1 高雄長庚紀念醫院 2 嘉義長庚紀念醫院

Background: Nucleos(t)ide analogues (NAs) are widely used for treatment of chronic hepatitis B (CHB) patients.The clinical outcomes of CHB patients improves significantly after using NAs, but the rate of hepatitis B surface antigen (HBsAg) loss is low during longterm treatment, and HBV relapse is common after the discontinuation of NA therapy.

Aims: This study compares the relapse rate of hepatitis B virus (HBV) between patients with HBV genotypes B and C after the cessation of either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy among HBeAg-negative chronic hepatitis B (CHB) patients.

Methods: The study enrolled 460 HBeAg-negative patients without cirrhosis who had stopped either ETV or TDF treatment for at least 12 months. All patients fulfilled the stopping criteria proposed by the APASL 2012 guidelines.

Results: Patients with HBV genotype B had significantly higher rates of virological and clinical relapse and retreatment than those with HBV genotype C among all patients and among patients matched by propensity score (PS). In addition, patients who discontinued TDF therapy had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued ETV therapy among all patients and PS-matched patients.

Multivariate analysis showed that TDF groups, old age, HBV genotype B, and higher end-or-treatment (EOT) HBsAg levels were independent factors of virological and clinical relapse. The 5-year virological and clinical relapse rates were low (19.2% and 15.4%, respectively) in patients with a combination of EOT HBsAg of 100 IU/ mL and HBV genotype C. The rates of off-therapy HBsAg loss, HCC development, and hepatic decompensation were comparable between patients with HBV genotypes B and C and between the ETV and TDF groups.

Conclusions: Patients with HBV genotype B had higher rates of virological and clinical relapse and retreatment than those with HBV genotype C after cessation of either ETV or TDF therapy among HBeAg-negative CHB patients.

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2020 消化系聯合學術演講年會

⑨

在血清轉胺脢僅輕微上升的慢性 B 型肝炎 患者以 Tenofovir 阻止病情進展：多中心雙 盲安慰劑對照隨機分派試驗 TENOFOVIR FOR PREVENTING PROGRESSION OF CHRONIC HEPATITIS B IN PATIENTS WITH MINIMALLY RAISED AMINOTRANSFERASE (TORCH-B): A MULTICENTER DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL 1,2

3

4

5, 6

7

8

許耀峻 陳啟益 張宜崴 吳俊穎 李騰裕 吳明賢 9 10 8 11 1 12 白明忠 陳志州 陳介章 曾政豪 戴啟明 顧文輝 13 14 牟聯瑞 林肇堂 1 義大醫院/ 義守大學 2 輔仁大學附設醫院 3 嘉義基督教醫院 4 臺北醫學大學附設醫院 5 陽明大學 6 臺北榮民總醫院 7 臺中榮民總醫院 8 臺灣大學附設醫院 9 馬偕紀念醫院臺東分院 10 奇美醫學中心 11 義大癌治療醫院/ 義守大學 12 臺北病理中心 13 市立臺南醫院 14 中國醫藥大學附設醫院

Background: Chronic hepatitis B (CHB) is the leading cause of liver-related morbidity and mortality worldwide.

Antiviral therapy is currently recommended for patients with CHB at advanced disease status. Whether treatment can prevent disease progression in patients with minimally raised alanine aminotransferase (ALT) is unclear.

Aims: To determine whether antiviral treatment prevents histopathological deterioration in patients with chronic hepatitis B presenting with minimally raised aminotransferase Methods: This multicenter, double-blind, placebocontrolled trial was conducted at 6 teaching hospitals in Taiwan (E-Da Hospital, Chiayi Christian Hospital, Taichung Veterans General Hospital, National Taiwan University Hospital-Yunlin Branch, Chi Mei Medical Center-Liouying Branch, and Mackay Memorial HospitalTaitung Branch). One hundred and sixty patients without liver cirrhosis or hepatic insufficiency who presented with serum ALT between 1~2 folds the upper limit of normal and

hepatitis B viremia above 2,000 IU/mL were enrolled from January 2012 through November 2015 and randomized to receive either tenofovir disoproxil fumarate (TDF) at a daily dose of 300mg or matching placebo continuously for 3 years. Entecavir was added in cases of hepatitis flare during the blinded trial. The primary efficacy outcomes were histological deterioration (≥2 points in increase of the Knodell necroinflammatory score or any worsening of fibrosis) and fibrosis progression (any increase in the Ishak scale) as determined by core liver biopsy. Analyses were done by the intent-to-treat principle, regardless of add-on entecavir (added in 13 placebo and 2 TDF receivers) Results: Among 160 patients enrolled, 79 and 81 patients were randomly allocated to TDF and placebo, respectively.

After 3-year treatment, 146 patients (n=73 in each group) completed the trial with paired liver biopsy. Histological deterioration occurred in 31.5% (n=23) and 57.5% (n=42) in the TDF and placebo group, respectively (P=0.03). The relative risk of TDF for histological deterioration was 0.55 (95% CI, 0.37~0.81). Liver fibrosis progressed in 26.0% (n=19) and 46.6% (n=34) in the TDF and placebo group, respectively (P=0.02). The relative risk for fibrosis progression was 0.56 (95% CI, 0.35~0.88). TDF achieved higher rates of viral and biochemical remission but the two groups were similar in serological outcomes. More patients in the placebo group (16.1% vs. 2.5%, P=0.005) experienced hepatitis events that required rescue therapy.

Conclusions: Antiviral therapy prevents histopathological progression in non-cirrhotic CHB patients who present with minimally raised ALT and significant viremia.

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2020 消化系聯合學術演講年會

⑩

比較停止化學治療後 6 個月和 12 個月的延 長預防性抗 B 型肝炎抗病毒治療 - 兩年追蹤 結果 TWO-YEAR FOLLOW-UP COMPARISONS OF THE DURABILITY OF 6 AND 12 MONTHS EXTENDED HBV PROPHYLAXIS ANTIVIRAL THERAPY AFTER CESSATION CHEMOTHERAPY 楊適宇 曾柏霖 周業彬 郭垣宏 蔡明釗 張國欽 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 Background: Prophylaxis antiviral therapy is r e c o mme n d e d for he pa t i t i s B pa t i e nt s re c eiving chemotherapy but the ideal treatment duration after cessation chemotherapy lakes clinical evidence.

Aims: To compare the relapse rate of short finite interval of 6 months and 12 months NA therapy in patients stratified by low HBV-DNA<2000 IU/ml or high HBV-DNA≥2000 IU/ml.

Methods: Patients received Tenofovir or Entecavir one week before chemotherapy and randomized into 4 groups after cessation chemotherapy: (1) HBV DNA<2000 IU/ ml, 6-month or 12-month duration (2) HBV DNA≥ 2000 IU/ml, 6-month or 12-month duration. Virological relapse (VR) was defined as HBV DNA > 2000 IU/ml and clinical relapse (CR) was defined as HBV DNA > 2000 IU/ml and ALT>80 IU/L during the follow-up. The primary endpoint was to compare the durability between groups.

Results: Sixty-one patients were enrolled and 5 patients were loss follow-up or tumor recurrence. Overall 2-year VR and CR rate was 53.6% and 14.3%, respectively. The VR rate was lower in 12-month consolidation group (p=0.008) but the CR rate was similar in each groups(p=0.53). VR rate was lower in patients with pre-treatment HBV-DNA <2000 IU/ml than that of HBV DNA≥ 2000 IU/ml. There was no difference of CR rate between the low and high HBV-DNA groups. End-treatment HBsAg level≥500 IU/ml was the predictor of virological relapse (adjust hazard ratio: 2.68; p=0.03).

Conclusions: Extended 12-month consolidation duration lower VR rate. Patients with HBV-DNA≥2000 IU/ml may receive longer consolidation therapy and those with end-treatment HBsAg level≥500 IU/ml should be closely monitored after cessation antiviral therapy in areas with limited budget.

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⑪

無肝硬化之慢性 B 型肝炎急性嚴重發作病 人停止使用抗病毒核苷類似物後肝炎復發 情形 HEPATITIS RELAPSE AFTER CESSATION OF NUCLEOS(T)IDE ANALOGUE THERAPY IN NONCIRRHOTIC PATIENTS WITH SPONTANEOUS SEVERE ACUTE EXACERBATION OF CHRONIC HEPATITIS B 賴佳業 李少武 蔡炘儒 黃耀光 楊勝舜 張繼森 李騰裕 臺中榮民總醫院 Background: HBsAg loss is a difficultly achieved target in the treatment of chronic hepatitis B (CHB), so cessation of nucleos(t)ide analogue (NA) therapy is a common realworld decision in non-cirrhotic patients. However, for patients with severe acute exacerbation (SAE) of CHB, the risk of NA therapy cessation has not been fully evaluated.

Aims: We aimed to assess the risk of hepatitis relapse after stopping NA therapy in non-cirrhotic patients who experienced CHB with SAE. Methods: In this hospital-based cohort study, we retrospectively screened CHB patients who received NA therapy due to CHB with SAE (bilirubin > 2 mg/ dL, prothrombin time prolongation > 3 seconds, HBV viral load > 2000 IU/ML, and alanine aminotransferase (ALT) > 5X upper limit of normal [ULN]), and then stopped NA therapy after achieving therapeutic endpoints (undetectable HBV viral load and negative HBeAg) during the period of 2003/10/01 to 2019/01/31. Exclusion criteria were as follows: currently active malignancy, liver cirrhosis, hepatitis C virus or human immunodeficiency virus co-infection, alcoholism, post-organ transplantation, immunotherapy, hepatitis other than CHB, mortality during NA therapy, and HBsAgseroclearance during NA therapy.

Cumulative incidences of hepatitis relapse, including SAE, severe hepatitis (ALT > 10X UNL), or clinical relapse (ALT > 2X ULN), were evaluated after cessation of NA therapy.

Results: In total, 72 non-cirrhotic patients with SAE of CHB were recruited for analysis in this study. The median age was 42.5 (25-75% IQR: 31.3-53.0) years old. Fiftyone (70.8%) patients were males, and twenty-one (29.2%) patients initially presented with positive HBeAg. Four kinds of NA were used (5.6% telbivudine, 44.4% lamivudine, 44.4% entecavir, and 5.6% tenofovir) for treating the SAE of CHB. The median duration of NA therapy was 36.0 (25-

2020 消化系聯合學術演講年會

主題：B 型肝炎（二） 75% IQR: 22.9-36.0) months. The median follow-up period was 18.6 (25-75% IQR: 8.5-35.8) months. The 5-year cumulative incidences of SAE, severe hepatitis flare, and clinical relapse were 31.2% (95% CI: 13.7-48.8%), 46.8% (95% CI: 30.2-63.4%), and 62.4% (95% CI: 48.4-76.3%), respectively. One patient died of SAE-related liver failure.

However, the 5-year cumulative incidence of HBsAg loss was 16.7% (95% CI: 0-33.4%).

Conclusions: Hepatitis relapse was common and usually severe after cessation of NA therapy in patients who received NA therapy for CHB with SAE. The hepatitis risk should be fully discussed with those patients before considering stopping NA therapy

⑫

比較 e 抗原陰性慢性 B 型肝炎病人停止惠 立妥後無再治療或再治療表命抗原改變的 比較 COMPARISON OF HBSAG CHANGE BETWEEN HBEAG-NEGATIVE CHRONIC HEPATITIS B PATIENTS WHO DISCONTINUED TENOFOVIR WITH AND WITHOUT RETREATMENT 1

1

1

2

2

陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 2 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科 Background: The changes of HBsAg and HBsAg loss rate after cessation of tenofovir disoproxil fumarate (TDF) remains unclear.

Aims: To compare the HBsAg change and HBsAg loss rates between HBeAg-negative patients who discontinued TDF with and without retreatment Methods: A total of 157 HBeAg-negative patients without cirrhosis who have stopped TDF treatment at least 12 months were recruited. All patients in discontinued group fulfilled the stopping criteria set forth by APASL 2012.

Results: Of the 157 patients, 51 had a persistent virological suppression (Group I), 31 had no virological suppression (HBV DNA>2000 IU/mL) after virological or clinical relapse without retreatment (Group II), 14 had virological suppression after transient virological or clinical relapse without retreatment (Group III), and 61 received retreatment (Group IV). The HBsAg levels at baseline were lowest in Group I (2.57±1.04 log IU/mL) compared to Groups II and IV (P<0.01). The HBsAg levels at the end of treatment were lowest in Group I (1.66±0.83 log IU/mL) compared to Groups II, III and IV (P<0.01).

To evaluate the correlation between different groups with post-treatment HBsAg changes, we conducted GEE analysis. Patients in Group I had significantly lower posttreatment HBsAg levels than patients in Groups II, III, and IV (all P<0.01). Patients in Group III had borderline lower HBsAg levels than patients in Groups II (P=0.054) and IV (P=0.074). Patients in Groups I exhibited a greater posttreatment HBsAg decline than patients in Groups II and IV (P<0.001), but not Group III (P=0.572). Patients in Group III had a borderline greater HBsAg decline than patients in Group IV (P=0.057).

The 4-year cumulative rates of post-treatment HBsAg loss in Groups I, II, III and IV were 27.2%, 0%, 7.1% and 2%, respectively (P<0.001).

Conclusions: Patients who discontinued TDF therapy and achieved persistent virological suppression (Group I) exhibited a greater HBsAg decline and higher HBsAg loss rate compared with other groups.

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⑬

較長鞏固治療時間可減少 E 抗原陰性患者 依照亞太肝病醫學會指引停用惠立妥後一 年內臨床復發的機率 LONGER CONSOLIDATION DURATION IS REQUIRED TO REDUCE 1-YEAR CLINICAL RELAPSE RATE AFTER STOPPING TENOFOVIR IN HBEAG NEGATIVE PATIENTS 1,3

2,3

1,3

1,3

鄭文睿 陳建宏 陳益程 沈一嫻 簡榮南 3,4 廖運範 1 林口長庚紀念醫院胃腸肝膽科系 2 高雄長庚紀念醫院胃腸肝膽科系 3 長庚大學醫學院 4 林口長庚紀念醫院肝臟研究中心

1,3,4

Background: Our recent report (AASLD 2019) showed no significant difference in the 1-year clinical relapse rate among overall 902 Nuc treated HBeAg negative CHB patients with a consolidation duration of 1-2, 2-3 and >=3 years. Comparing with ETV, TDF therapy is associated with much earlier off-therapy relapse. Whether consolidation duration required to be longer in this population remained unknown.

Aims: To compare the optimal length of consolidation treatment in terms of 1-year clinical relapse (CR: HBV DNA >= 2000IU/ml + ALT >=2X ULN) rate between ETV and TDF treated patients.

Methods: HBeAg negative CHB patients from two tertiary medical centers received ETV or TDF and had stopped therapy after demonstration of undetectable HBV DNA for more than 1 year with off-Nuc followed-up >= 1 year were recruited. The 1-year CR rate was compared among patients with consolidation therapy of 1-2 years vs. >= 3 years. Propensity score matching with age, cirrhotic status, prior treatment history, the proportion of EOT HBsAg categorized level (>200, 200-100, <100 IU/ml) at 1:1 ratio was performed to adjust the characteristics between off ETV and off TDF patients. Kaplan-Meir analysis and the log-rank test was performed to compare the consolidation duration impact on off ETV or TDF 1-year clinical relapse rate.

Results: A total of 428 patients were included, with 214 patients in each group. Age, EOT age, gender, cirrhotic status, genotype, prior treatment history and proportion in EOT HBsAg > 200,100-200,<100IU/ml were comparable between off ETV and TDF group. In Kaplan Meir analysis, the 1-year CR rate was significantly lower in off-TDF

62

patients with consolidation > 2 years than those < 2 years (37.7% vs. 61.7%, log-rank test, P=0.001) whereas there was no difference (30.8% vs. 35.2%, log-rank test, P=0.400) in off-ETV patients.

Conclusions: The results have demonstrated that consolidation duration in off-TDF patients may require longer period > 2 years to reduce the off-Nuc 1-year clinical relapse rate

2020 消化系聯合學術演講年會

⑭

以 HBsAg 預測 B 型肝炎相關肝癌手術切除 後早期及晚期復發之預後模式 HBSAG-BASED MODELS STRATIFY RISK OF EARLY AND LATE RECURRENCE AFTER CURATIVE RESECTION OF HBV-RELATED HEPATOCELLULAR CARCINOMA 1,2

3

1,2

1,2

1,2

1,2,4

李懿宬 周嘉揚 蘇建維 林漢傑 侯明志 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院外科部 4 國立陽明大學臨床醫學研究所

Background: The risk of recurrence is high even under nucleos(t)ide analogues (NUCs) treatment in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection.

Aims: The aim of this study was to evaluate the role of HBsAg in patients receiving curative resection for HBVrelated HCC in NUCs era.

Methods: Consecutive 551 patients receiving curative resection for HBV-related HCC with available serum HBsAg levels were retrospectively enrolled, including 67.2% patients with NUCs treatment after surgery. In patients without NUC therapy, 63.2% had low HBV viral load (< 2000 IU/mL). Factors associated with early and late recurrence were evaluated.

Results: During a median follow-up of 50.5 months, 201 (36.5%) and 84 (15.2%) patients developed early and late recurrence, respectively. By multivariate analysis, BCLC stage B-C (hazard ratio (HR)=2.170, p<0.001), HBsAg >200 IU/mL (HR=1.766, p=0.006), ALBI grade 2-3 (HR=1.454, p=0.035), and presence of microvascular invasion (HR=1.802, p=0.016) were independent predictors of early recurrence. HBsAg >200 IU/mL (HR=1.851, p=0.048), Ishak inflammation score >6 (HR=2.820, p=0.011) and cirrhosis (HR=1.951, p=0.020) were independent predictors of late recurrence. Predictive models based on HBsAg levels were developed and could discriminate patients into 3 risk groups of early recurrence (2-year recurrence rate of 22.2%, 32.8% and 56.7%, respectively, p<0.001) and late recurrence (5-year recurrence rate of 10.4%, 28.7% and 50.3%, respectively, p<0.001).

Conclusions: The HBsAg-based models could classify patients into three risk groups of early and late recurrence, and would guide post-operative surveillance program and select patients who need adjuvant therapy for clinical trials design.

⑮

貝樂克或惠立妥治療停藥病人有臨床復發 後再治療或持續病毒抑制之預測因子 THE PREDICTORS OF RETREATMENT OR PERSISTENT VIROLOGICAL SUPPRESSION AFTER CLINICAL RELAPSE IN PATIENTS WHO DISCONTINUED ENTECAVIR OR TENOFOVIR THERAPY 1

1

1

1

2

2

方信為 陳建宏 王景弘 胡琮輝 洪肇宏 盧勝男 1 高雄長庚紀念醫院胃腸肝膽科系 2 嘉義長庚紀念醫院胃腸肝膽科系

Background: The predictors of retreatment or persistent virological suppression without retreatment after clinical relapse (CR) in patents who discontinued nucleot(s)ide analogues (NA) therapy remains unclear.

Aims: To investigate the predictors of retreatment or virological suppression after CR in patients who discontinued entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy.

Methods: A total of 229 HBeAg-negative patients without cirrhosis who experienced CR after the cessation of ETV or TDF for at least 12 months were enrolled.

All patients fulfilled the stopping criteria by the APASL 2012 guidelines. The criteria for retreatment in Taiwan’s National Health Plan are two instances of ALT ≥ 2 × ULN at 3 months apart and HBV DNA ≥ 2000 IU/mL, and hepatic decompensation are total biliruin ≥ 2 mg/dL or PT prolongation ≥ 3 seconds, regardless of HBV DNA levels.

Results: Of the 229 patients, 169 received retreatment and 60 did not received retreatment (27 achieved persistent virological suppression without retreatment) after CR. All patients who received retreatment met the stopping criteria of Taiwan’s National Health Plan. The multivariate analysis showed that young age at entry and lower HBsAg levels at the first CR were independent factors of patients who achieved persistent virological suppression.

The HBsAg cut-off value at the first CR for predicting virological suppression without retreatment was 107.4 IU/ mL (AUROC: 0.772). The rates of virological suppression in patients with HBsAg <100 and ≧ 100 IU/mL at the first CR were 48% and 6.9% (p<0.001), respectively. TDF therapy, old age at entry, higher baseline HBsAg level and HBsAg change from first CR to end of treatment were independent factors of retreatment. The 6-year cumulative rates of HBsAg loss in patients with and without persistent virological suppression after stopping ETV or TDF therapy were 31.7% and 2.9% (p<0.001).

Conclusions: The HBsAg level at the first CR could predict virological suppression or retreatment after CR in patients who discontinued ETV or TDF therapy.

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⑯

細胞核運輸抑制和 B 型肝炎病毒複製的關 係：新穎的 B 型肝炎治療標的 NUCLEAR TRANSPORT INHIBITION AND HBV REPLICATION:A POTENTIAL THERAPEUTIC TARGET FOR HBV 1,2

1,2

1,2

1,2

蔡維倫 鄭錦翔 孫煒智 陳文誌 張聰賢 1 高雄榮民總醫院腸胃科 2 國立陽明大學醫學院 3 國防醫學院, 微生物及免疫學科暨研究所

3

Background: Chronic hepatitis B virus (HBV) infection is the leading cause of cirrhosis or hepatocellular carcinoma (HCC) in Taiwan. However, there remained no effective therapy to cure HBV. Nuclear transport is essential for the replication of many DNA virus or retrovirus in their life cycles. But the role of nuclear transport inhibition in HBV replication remained unclear.

Aims: The aim of the study is to screen and identify the molecules associated with nuclear transport and replication of HBV Methods: The HepG2.2.15 cells were used in the experiments. Lentivirus mediated short hairpin RNA (shRNA) knock-down of candidate genes were done.

Quantification of supernatant HBsAg and HBV DNA were performed. Cell viability assay was conducted. Q-PCR to evaluate efficiency of knock-down of candidate genes were performed.

Results: We screened many molecules associated with nuclear transport in hepatocytes and investigated the influence of these molecules on HBV replication. We have identified that several molecules associated with nuclear transport including Nucleoporin (Nup) -50 and several other molecules, A, B and C were related with HBV replication. Lentivirus mediated shRNA knock-down of Nup-50 and molecules A, B and C in HepG2.2.15 cells significantly reduced the level of HBsAg in supernatant at 3 and 5 days. Supernatant HBV DNA was checked in the shRNA knock-down of Nup50 cells. HBV DNA at 5 days in the supernatant was decreased in shRNA mediated knock-down of Nup50 in HepG2.2.15 cells. shRNA mediated knock-down of these candidate genes did not influence cell viability in HepG2.2.15 cells. Q-PCR found that shRNA mediated knock-down of these candidate genes are effective.

Conclusions: We have found that inhibition of Nup50 and three novel molecules associated with nuclear transport of hepatocytes significantly reduced HBV replication. Our

64

ongoing studies are to investigate the molecular mechanism of Nup50 and another three novel molecules associated with nuclear transport and HBV replication. Nuclear transport inhibition may be a potential therapeutic target for future anti-HBV treatment

2020 消化系聯合學術演講年會

主題：肝腫瘤（一）

⑰

具肝硬化與高 modified FIB-4 指標之慢性 B 型肝炎患者接受貝樂克治療前 7 年具有高肝 癌年發生風險 INCREASED ANNUAL RISK OF HEPATOCELLULAR CARCINOMA PERSISTS UP TO 7 YEARS OF ENTECAVIR THERAPY IN CHRONIC HEPATITIS B PATIENTS WITH BASELINE CIRRHOSIS AND HIGHER MODIFIED FIB-4 VALUE 1

2

1

2

2

1

王鴻偉 陳建宏 賴學洲 胡琮輝 王景弘 彭成元 1 中國醫藥大學附設醫院消化醫學中心 2 高雄長庚紀念醫院內科部胃腸肝膽科系

Background: Long-term nucleos(t)ide analogue (NA) therapy reduces the cumulative incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, the dynamic changes in the annual HCC incidence and its risk stratification by baseline liver fibrosis status and non-invasive fibrosis index remain unclear.

Aims: We aimed to investigate the annual incidence of HCC stratified by baseline liver fibrosis status (cirrhosis or not) and non-invasive fibrosis index (FIB-4 and modified FIB-4 (mFIB-4)) in patients with CHB who received NA therapy.

Methods: A total of 1325 prior NA-naïve CHB patients receiving entecavir therapy were enrolled from January 2007 to August 2012. Baseline clinical characteristics and laboratory data were collected. Liver cirrhosis was identified by either liver biopsy or ultrasonographic diagnosis. The optimal cutoff values of non-invasive indices in predicting HCC were identified by receiver operating characteristic (ROC) curve analysis and the Youden index. Annual HCC incidence was calculated and compared among subgroups stratified according to the combinations of baseline cirrhosis status and non-invasive fibrosis index.

Results: A total of 105 patients developed HCC. Baseline mFIB-4 showed higher predictive performance for HCC compared to FIB-4 either in cirrhotic patients (AUC: 0.63 vs 0.61, P = 0.277) or non-cirrhotic patients (AUC: 0.76 vs 0.65, P = 0.003). The optimal cutoff value of mFIB-4 in predicting HCC in cirrhotic (n = 481) and non-cirrhotic (n = 844) patients was 5.92 and 3.68, respectively. Patients with baseline cirrhosis and mFIB-4 ≥5.92 continued to exhibit the highest annual HCC incidence up to 7 years of treatment, compared to those with baseline non-cirrhosis

and mFIB-4 <3.68 who exhibited the lowest annual HCC incidence (1-2 yr: 10.07% vs 0%, P <0.001; 2-3 yr: 6.78% vs 0.44%, P <0.001; 3-4 yr: 12.24% vs 0.17%, P <0.001; 4-5 yr: 5.33% vs 0.68%, P = 0.017; 5-6 yr: 5.17% vs 0%, P = 0.01; 6-7 yr: 9.68% vs 0%, P = 0.005). Patients with baseline cirrhosis and a decline in mFIB-4 at one year of treatment exhibited a numerically lower annual HCC incidence over Year 1 to 5 compared to those with cirrhosis and an increase in mFIB-4 at one year of treatment (1-2 yr: 4.17% vs 5.97%, P = 0.514; 2-3 yr: 3.23% vs 4.01%, P = 1.000; 3-4 yr: 2.78% vs 7.95%, P = 0.101; 4-5 yr: 0% vs 6.10%, P = 0.023).

Conclusions: A combination of baseline liver cirrhosis status and mFIB-4 could identify the subgroup of patients with CHB undergoing long-term entecavir therapy at higher annual risk of HCC up to 7 years of treatment.

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2020 消化系聯合學術演講年會

⑱

C 型肝炎相關肝癌手術切除後復發及存活之 預測因子 PREDICTORS OF RECURRENCE AND SURVIVAL AFTER CURATIVE RESECTION IN PATIENTS WITH HCV-RELATED HEPATOCELLULAR CARCINOMA 1

1,2

1

3

1,2

1,2,4

胡果正 李懿宬 齊振達 周嘉揚 侯明志 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院外科部 4 國立陽明大學臨床醫學研究所

Background: Predictors of recurrence and survival after curative resection in patients with hepatitis C virus (HCV)related hepatocellular carcinoma (HCC) remains unclear.

Aims: The aim of this study was to evaluate the predictors of recurrence and survival in patients receiving curative resection for HCV-related HCC. Methods: Consecutive 283 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 96 (33.9%) and 65 (23%) patients with interferon and direct-acting antivirals (DAA) treatment, respectively, either before or after surgery. Factors associated with early recurrence within two years and late recurrence after two years of surgery as well as overall survival (OS) were evaluated.

Results: During a median follow-up period of 44.5 months, 95 (33.6%) and 48 (17%) patients developed early and late recurrence, respectively, and 98 (34.6%) patients died. 73 (76%) and 62 (95.4%) of patients treated with interferon and DAA achieved sustained virological response (SVR), respectively. By multivariate analysis, tumor size >5 cm (hazard ratio (HR)=2.335, p<0.001), multiple tumors (HR=1.768, p=0.016), and aspartate aminotransferase >40 U/L (HR=1.803, p=0.011) were independent predictors of early recurrence. Gamma-glutamyl transferase (GGT) >75 U/L (HR=2.004, p=0.038) was the only independent predictor of late recurrence. Tumor size >5 cm (HR=1.668, p=0.033), FIB-4 score >3.25 (HR=1.889, p=0.003), and achieving SVR by either interferon-based treatment (HR=0.366, p<0.001) or DAA (HR=0.165, p<0.001) were independent predictors of OS. Conclusions: Tumor factors are associated with early recurrence while GGT was a predictor of late recurrence in patients with HCV-related HCC undergoing curative resection. Achieving SVR by either interferon or DAA therapy was associated with a significant reduction in mortality after surgery.

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⑲

預測經射頻燒灼術後復發小型肝癌病患之 預後 PREDICTING OUTCOMES FOR RECURRENT HEPATOCELLULAR CARCINOMA WITHIN MILAN CRITERIA AFTER COMPLETE RADIOFREQUENCY ABLATION 1

2

1

1

2

1

陳興曄 盧勝男 王景弘 陳建宏 洪肇宏 顏毅豪 1 1 郭垣宏 紀廣明 1 高雄長庚紀念醫院胃腸肝膽科系 2 嘉義長庚紀念醫院胃腸肝膽科系

Background: Intrahepatic recurrence is a significant problem for patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC).

Aims: The objective of the study is to investigate risk factors and to predict outcomes of recurrent HCC within Milan criteria after complete RFA for primary early-stage HCC. Methods: This retrospective study reviewed 368 patients with recurrent HCC that tumor number <=3 and tumor size <= 3cm after complete RFA for early-stage HCC in Kaohsiung Chang Gang Memorial hospital during June 2003 to October 2018, and 65 patients with local recurrence were excluded. A total of 303 patients were included and their baseline characteristics, further treatment modalities after tumor recurrence and survival were analyzed.

Results: After a median follow-up of 39.5 months, 55 patients had died. The majority of patients were male (59.9%) with median age of 66 years (range:38-88).

The cumulative 1-, 3-, and 5-year overall survival (OS) rates after treatment for recurrent HCC was 97.2%, 86.6% and 76.8%, respectively. On univariate analysis, female gender, patient age older than 65 years, an aspartate aminotransferase level higher than upper limit, Child-Pugh classification B or C, leukopenia, anemia, thrombocytopenia, the 2nd recurrence developed within 6 months after treatment, ALBI grade 2 or 3, and APRI index >1 were significant risk factors for OS. Further multivariate analysis results showed that age older than 65 years (Hazard ratio(HR): 2.3, 95% CI, 1.21-4.34, p<0.01), presence of hypertension (HR:2.05, 95% CI, 1.21-4.34, p=0.014), ALBI grade B or C (HR:3.719, 95% CI, 1.9-7.27, p<0.001), and shorter time to 2nd recurrence (HR:2.97, 95% CI, 1.675.27, p<0.001) were associated with worse survival. The cumulative 1-, 3-, and 5-year recurrence rates was 41.1%, 79.2% and 89.3%, respectively. On univariate analysis,

2020 消化系聯合學術演講年會

patient age older than 65 years, alcohol use, an α-fetoprotein level greater than 20 ng/mL, higher serum creatinine level, APRI index >1, ALBI grade 2 or 3, anemia, thrombocytopenia, tumor number > 1, 1st HCC recurrence developed within 1 year after RFA, were associated with higher risk of 2nd recurrence. On multivariate analysis, patient age older than 65 years (HR:1.63, 95% CI, 1.242.15, p<0.001), alcohol use (HR: 1.66, 95% CI, 1.232.23, p=0.001), an α-fetoprotein level greater than 20 ng/ mL (HR: 1.56, 95% CI, 1.18-2.04, p=0.001), higher serum creatinine level (HR: 1.13, 95% CI, 1.04-1.24, p=0.004), thrombocytopenia (HR:1.448, 95% CI, 1.07-1.95, p=0.015), tumor number> 1 (HR: 1.499, 95% CI, 1.1261.995, p=0.006), the time to 1st recurrence (HR:0.991, 95% CI, 0.984-0.997, p=0.002) and non-surgical treatment for HCC recurrence (HR: 2.49, 95% CI, 1.08-5.75, p=0.032) are prognostic factors for re-recurrence.

Conclusions: Our study suggested that age older than 65 years, hypertension, ALBI grade and time to 2nd HCC recurrence were associated with overall survival while the 2nd HCC recurrence was associated with alcohol use, age, α-fetoprotein level >20 ng/mL, thrombocytopenia, nonsurgical therapy, time to 1st recurrence, and tumor number > 1.

⑳

從 TCGA 肝細胞癌資料庫分析獲得的五個 長非編碼 RNA(lncRNA) 所組成預後指標的 臨床預後效益評估 5‐LNCRNA PROGNOSTIC SIGNATURE FOR HEPATOCELLULAR CARCINOMA FROM TCGA DATABASE 1,2

2

2

2

3

王嗣仁 蔡青陽 孫盟舜 陳錫榮 戴嘉言 余明隆 1 高雄醫學大學臨床醫學研究所 2 阮綜合醫院消化內科 3 高雄醫學大學附設醫院肝膽胰內科暨肝病中心

3

Background: Current studies showed that long noncoding RNAs (lncRNAs) may play the role of prognostic biomarkers in various cancers. This study aimed to find a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis from The Cancer Genome Atlas(TCGA) database.

Aims: This study aimed to find a long non-coding RNA (lncRNA) signature for predicting hepatocellular carcinoma (HCC) prognosis from The Cancer Genome Atlas(TCGA) database.

Methods: 1. LncRNAs expression profiles and corresponding clinicopathological data for 374 patients with HCC were obtained from The Cancer Genome Atlas (TCGA), including 374 tumor-part specimens and 50 nontumor-part specimens.

2. Differentially expressed lncRNAs (DELs) between tumor-part and non-tumor-part specimens of hepatocellular carcinoma(HCC) were identified using the edgeR package, using an false discovery rate (FDR) < 0.05 and log2 |fold change(FC)| > 2.

3. The least absolute shrinkage and selection operator Cox (LASSO Cox) regression model was used to identify the lncRNA signature.

4. Next, the key lncRNAs in Lasso Cox regression were further analyzed with a stepwise multivariate Cox regression model. The lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were selected to construct a prognostic risk formula.

5. The R software version 3.6.1 and the “edgeR”, “glmnet”, “survival”, “timeROC” and “survminer” package were utilized to analysis.

6. The risk scores were calculated based on the formula generated through the multivariate Cox regression model.

Using the median risk score as the cutoff value, patients in the dataset were divided into low‐risk or high‐risk groups

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correspondingly.

7. The efficiency of the predictive model was estimated by the Receiver operating characteristic curve(ROC curve) and Harrell’s C-index statistic.

Results: Based on lncRNA expression profiling of 374 HCC patients from the TCGA database, a total of 1292 DELs were selected out including 80 down-regulated DELs and 1212 up-regulated DELs(Fig. 1). 6 lncRNAs were identified using LASSO Cox. Finally, 5 lncRNAs(AC015712.7, AC015722.2, LINC00462, LINC01297 and SRGAP3AS2) were confirmed in multivariate Cox regression model(Fig. 2). According to this 5-lncRNAs signature, the corresponding AUC for the predictive model of 3-year and 5-year survival was 0.689 and 0.647, respectively(Fig. 3).

It had a Harrell’s C-index statistic of 0.679(95%CI:0.540.81), indicating a near moderate predictive ability for survival time of HCC. Kaplan-Meier analysis revealed that for the TCGA cohort, the high-risk group had significantly poorer survival than the low-risk group(Log-Rank test p=2.579e-0.5)(Fig. 4).

Conclusions: Our study constructed the 5-lncRNA model can be a biomarker to predict the prognosis of HCC. Further studies were needed to confirm this signature.

68

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驗證改良式 ALBI-TNM 分級用於預測早期 肝癌患者接受射頻灼燒術的預後 VALIDATION OF MODIFIED ALBUMIN-BILIRUBIN-TNM GRADE AS A PROGNOSTIC PREDICTION IN PATIENTS WITH EARLY-STAGE HEPATOCELLULAR CARCINOMA UNDERGOING RADIOFREQUENCY ABLATION 1

2

1

1

2

1

葉文碩 盧勝男 王景弘 陳建宏 洪肇宏 顏毅豪 1 1 郭垣宏 紀廣明 1 高雄長庚紀念醫院胃腸肝膽科系 2 嘉義長庚紀念醫院胃腸肝膽科系

Background: Modified albumin-bilirubin (mALBI) grade is currently a good tool for assessment of hepatic reserve function in hepatocellular carcinoma (HCC) patients.

Aims: The aim of this study was to validate the modified albumin-bilirubin-TNM (mALBI-T) grade as a prognostic prediction model for patients with very early or early stage HCC undergoing radiofrequency ablation (RFA).

Methods: From January 2002 to September 2016, patients diagnosed with naïve HCC, Barcelona Clinic Liver Cancer (BCLC) stage 0 and A and treated with RFA as first therapy were enrolled in this study. According to previous study, we used -2.270 (divide grade 2 to 2a and 2b) as an additional cutoff value for ALBI score to divide ALBI grade into 4 levels (mALBI) that might provide a more detailed assessment of hepatic function. Child-Turcotte-Pugh (CTP) score, ALBI, mALBI, and platelet-ALBI (pALBI) were estimated as hepatic function and combined with 8th edition TNM stage. Akaike’s Information Criterion (AIC) and c-index values were analyzed for all scoring system to find a better prognostic prediction model for these patients.

All patients were followed-up until dead or the end of the study in December 2018.

Results: A total of 950 patients were included in this study (591 males and 359 females with a mean age of 64.2±10.3 years). The one-, 3-, 5-year overall survival (OS) was 94.6%, 73.6% and 58.0%, respectively.Among CTP, ALBI, mALBI, pALBI grading, the results showed there were significant survival differences between each group (p<0.01) and exist a linear trend(P<0.001). After combined with 8 th TNM stage, AIC and c-index for mALBI-T (5052.3/0.689) were better than CTP-T (5106.1/0.613), ALBI-T (5069/0.663), pALBI-T (5083.7/0.661). In subgroup, the AIC/n and c-index for mALBI-T in CTP

2020 消化系聯合學術演講年會

class A patients (4.84/0.682) were better than in CTP class B patients (5.25/0.507).

Conclusions: The mALBI-T represented the best stratification ability and prognostic prediction in earlystage HCC who undergoing RFA if compared with CPT-T, ALBI-T, pALBI-T. Beside, mALBI-T has better prognostic prediction in CTP class A than CTP class B patients.

㉒

肝癌治療成效追蹤與術後復發預測輔助系 統 ARTIFICIAL INTELLIGENCE ASSISTED PREDICTION SYSTEM OF HEPATOCELLULAR CARCINOMA TREATMENT EFFICACY AND POST TREATMENT RECURRENCE. 1

3

3

2

4,5

梁嘉德 楊大煒 陳柏文 吳耀銘 周承復 1 國立臺灣大學醫學院附設醫院胃腸肝膽科 2 國立臺灣大學醫學院附設醫院一般外科 3 國立臺灣大學資訊網路與多媒體研究所 4 國立臺灣大學資訊工程系暨研究所 5 臺大醫院資訊室 Background: According to research, the probability of liver cancer recurrence within 50 years is 50-60%. Tumor resection and RFA are the most widely used curative treatment methods today. The proportion of complications caused by treatment is getting lower and lower, but receiving curative treatment after the recurrence rate remains high, it is also the main cause of patient death.

Currently, the effectiveness of curative treatment in Taiwan has not been systematically tracked, which has led to unpredictable postoperative recurrence.

Therefore, it is hoped that by establishing a system for tracking the effectiveness of liver cancer resection and RFA and the prediction of postoperative recurrence rate, the pretreatment and post-treatment data will be analyzed, and the high-risk groups with recurrence will be identified for close tracking. It is hoped that there will be opportunities to reduce liver cancer Chance of relapse to death.

Aims: Early stages of hepatocellular carcinoma (HCC) can be curatively treated radiofrequency ablation (RFA) and surgery, but the recurrence rate is still high. We currently cannot accurately identify the high-risk patients with recurrence by existing relevant statistical studies with inconsistent results. Plenty of studies using conventional statistical methods to predict the recurrence of cancer have been published. However, research of artificial intelligence (AI) assisted construction of predictive models for the HCC recurrence is still limited. We want to construct a HCC recurrence prediction model by using AI techniques, further reducing the proportion of relapses after receiving curative treatment.

Methods: Our HCC recurrence prediction model is trained with 334 patients’ clinical records collected in database form National Taiwan University Hospital (NTUH)

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主題：肝硬化及其他肝病 between 2007 and 2013. The patients were all newly diagnosed early stage HCC who received RFA as the first treatment. There are 256 patients did not have recurrent HCC one year after RFA treatment and the other 78 patients had HCC. We extracted 16 HCC related features among patient’s clinical information, blood test data, ultrasound report, etc. Further, we construct the patient-based package report with these features as the data input for AI training.

To develop the HCC recurrence prediction model, which outputs whether the input patient report will have HCC recurrence in one year, we have tried several type of AI methods including support vector machine (SVM), random forest (RF), and deep neural network (DNN). Afterwards, we compared the performance of model among different methods.

Results: We use the following metrics to evaluate performance of our models with different AI methods: accuracy (ACC), sensitivity (SEN), specificity (SPE), and balanced accuracy (BAC) which is the average of SEN and SPE. The compared result is shown in the table.

The method “RF+SVM” means we first apply random forest classifier to the whole dataset, and then add feature stepwise according to feature weights given by the classifier. With each feature subset, do the grid search to find best result. “SA+RF+SVM” is further use simulated annealing for feature selection before applying RF to assign feature weights. The accurate rate of our current prediction model is about 70% by SVM, while DNN improves that to 80% with almost the same balanced accuracy.

Conclusions: We utilized the collected HCC patients’ clinical records in NTUH to build a prediction model of HCC recurrence after RFA and validated different AI analysis methods. In summary, the DNN method achieved best results by considering both accuracy and balanced accuracy. There is room for improvement in accurate rate for our research.

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利用機器學習及資料擴增方法偵測超音波 肝硬化 ULTRASONOGRAPHIC LIVER CIRRHOSIS DETECTION ASSISTED

BY MACHINE LEARNING AND IMAGE AUGMENTATION 1, 2

3

3

1,2,4,5

蘇東弘 張皓鈞 蔡明哲 高嘉宏 1 臺大醫院胃腸肝膽科 2 臺大醫院肝炎研究中心 3 康濰醫慧有限公司 4 臺大醫學院臨床醫學研究所 5 臺大醫院醫學研究部 6 臺大醫院影像醫學部

3

6

楊凱傑 吳志宏

Background: Liver cirrhosis is usually detected by abdominal ultrasonography; however, the sensitivity and specificity were low because ultrasonography is largely operator-dependent. To identify key morphological features of the images may improve the diagnostic accuracy for liver cirrhosis.

Aims: To investigate whether machine learning assisted feature extraction can help the ultrasonographic diagnosis of liver cirrhosis.

Methods: This is a retrospective cohort study to collect ultrasonographic images of liver. Fibrosis stages (F0-4) were determined by shear wave velocity from acoustic radiation force impulse (ARFI) imaging during routine abdominal ultrasonographic examination. Images with cirrhosis (F4) or normal (F0) were collected and then randomly split into either the training set or the validation set in a ratio of 8:2. From each image of the training set, additional region of interest (ROIs) with similar ultrasonographic texture were selected manually, to augment the training samples. These training ROIs were used for model establishment. The texture features derived from training images, like properties of grey-level cooccurrence matrix, were used to train non-neural-network models. The accuracy, sensitivity, and specificity of models on the validation set were measured.

Results: The original training set contained 362 cirrhosis and 220 normal ultrasonographic images. By adding additional ROIs, these numbers were augmented to 558 and 585, respectively. Meanwhile, the validation set contained 92 cirrhosis and 55 normal images. In the validation set, Support-vector scored the highest accuracy of 80.6% and achieved 72.7% specificity and 85.7% sensitivity. We also ensembled multiple models including the Support

2020 消化系聯合學術演講年會

Vector Machine, Logistic Regression, and the Elastic Net by taking the average of predictions, resulting in 83.7% accuracy, 72.7% specificity and 90.2% sensitivity.

Conclusions: We trained various models for classifying liver cirrhosis from normal ultrasonographic images and obtained acceptable performance. Our results suggested image recognition could be applied in abdominal ultrasound to help the detection of liver cirrhosis.

㉔

shear wave elastography 對後期肝纖維化的 診斷準確度 DIAGNOSTIC PERFORMANCE OF SHEAR WAVE ELASTOGRAPHY IN ADVANCED LIVER FIBROSIS 1

2

1

1

1

1

黃耀光 王任卿 李少武 蔡炘儒 楊勝舜 張繼森 1 李騰裕 1 臺中榮民總醫院內科部胃腸肝膽科 2 臺中榮民總醫院病理部

Background: Evaluation the severity of liver fibrosis is important in the diagnosis and treatment of liver disease.

Although liver biopsy is the gold-standard test for assessment of liver fibrosis but is invasive. Therefore an accurate non-invasive test is helpful in evaluating liver fibrosis.

Aims: The aim of this study was to evaluate the validity of shear-wave elastography in the diagnosis of advanced liver fibrosis.

Methods: In this prospective trans-sectional study, consecutive 78 patients who underwent liver biopsy were recruited from February, 2017 to October, 2019. Liver tissues were evaluated by two independent pathologists with the Metavir fibrosis score system from F0 to F4.

Shock wave elastography was measured with an Aplio 500 Platinum Series ultrasound machine. The Fib-4 and APRI value were calculated at the same time. The cut-off values for severe fibrosis(Metavir stage ≥F3) were determined with receiver operating characteristic (ROC) analysis. The accuracy was compared between shear wave elastography, Fib-4 and APRI. Results: The median age of the patients was 60.0 (25%75% IQR: 49.8-69.0) years old, and 44 patients (56.4%) were males. The median shear-wave speed measured were 1.85 m/s (1.59-2.15). In addition, 38 (48.7%) and 35 (44.9%) patients were HBV and HCV carriers, respectively.

The median Fib-4 value was 2.55 (25%-75% IQR: 1.504.10), and The median APRI value was 0.91 (25%-75% IQR:0.55-1.45). Using an optimal cutoff value of 1.87 m/s, the sensitivity and specificity in the diagnosis of advanced fibrosis were 83.3% and 88.1%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 90.9% and 86.1%, respectively. Comparing to Fib-4 (sensitivity 69.4% and specificity 71.43%) and APRI (sensitivity 94.4% and specificity 50.0%), the shear wave elastography may be a superior modality in detecting advanced fribosis (P< 0.001).

Conclusions: In this prospective study, the shear wave elastography can be a valid non-invasive method in the detection of advanced liver fibrosis.

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㉕

㉖

蔡宗憲 張經緯 王蒼恩 陳銘仁 朱正心 馬偕紀念醫院腸胃內科 馬偕醫護管理專科學校 馬偕醫學院

朱祐龍 曾岱宗 蘇東弘 賴台軒 陳世宜 林水龍 1,2,3,4 1,2,3 1 1,2,3,4,5 1,2,3,4,5 劉俊人 劉振驊 楊宏志 陳培哲 高嘉宏 1,2,3,4,6 陳定信 1 臺大醫院內科部胃腸肝膽科 2 臺灣大學醫學院內科部 3 臺大醫院肝炎研究中心 4 臺大醫院肝炎研究中心 5 臺大醫院醫學研究部 6 中央研究院基因體研究中心 7 臺大醫院內科部腎臟科

肝膿瘍在老人之臨床表現：單一醫學中心臨 床經驗研究 LIVER ABSCESS IN EXTREMELY ELDERLY PATIENTS: A REAL-WORLD EXPERIENCE IN A SINGLE TERTIARY MEDICAL CENTER EXPERIENCE IN TAIWAN

Background: Liver abscesses are the most common type of visceral abscess. It could be life-threatening condition for elderly population. The majority of these abscesses are categorized into pyogenic or amoebic, although a minority is caused by parasites and fungi. Timely intervention including surgical debridement or percutaneous drainage method in combination with broad-spectrum antibiotics could be help for the elderly populations.

Aims: This study is aimed to analysis the real-world experience in treatment for the elder populations (age more than 65 years-old) with liver pyogenic abscess.

Methods: A retrospective study in Mackay Memorial Hospital, Taipei, Taiwan was performed for analysis for elderly patients with liver abscess including demographics, blood and pus cultures.

Results: From Aug 2008 to Aug 2018, there are 129 patients who were admitted for liver abscess in Mackay Memorial Hospital, Taipei, Taiwan. The ratio for male to female is 52% to 48%. The mean age of patients is 76.51 ± 8.02. Time of Hospitalization (Days) is 23.39 ± 19.34.

Time from symtpoms to diagnosis (Days) is 5.09 ± 4.21.

The rate of smoking and alcoholism is 7.7% and 3.7% separately. The most common co-morbidity is hypertension (52.88%), diabetes mellitus (49.60%), and coronary artery disease (22.00%). Fever and chills are most common initial presentations of symptoms followed by epigastric and right abdominal pain, nausea and vomiting, and hypotension.

The most common bacteria in abscess culture are Klebsiella pneumonia (31.01%), E coli (8.53%) and Enterococcus (3.1%). Relatively in blood are Klebsiella pneumonia (34.88%), E coli (7.75%) and viridans streptococci (3.1%).

Conclusions: Liver abscess formation is a critical condition for those with elder age and co-morbidities. The elderly age, ICU admissions and hypotension have a worse prognosis. To identify the pathogen and early intervention could be life saving especially for those with patients with elderly age.

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血液透析患者 B 型及 C 型肝炎流行病學及 治療現狀 THE EPIDEMIOLOGY AND MANAGEMENT OF HEPATITIS B OR C IN PATIENTS UNDERGOING HEMODIALYSIS: A PROSPECTIVE COHORT STUDY 1

1,2,3

1,2

7

7

7

Background: The transmission routes for viral hepatitis B and C include blood transfusion, percutaneous exposure such as medical procedures or injections. The epidemiology of acute or chronic hepatitis B or C infection in hemodialysis center in Taiwan remains unclear.

Aims: Our aim was to explore the incidence of acute hepatitis B, or C, and the prevalence as well as management of chronic hepatitis B or C in hemodialysis centers.

Methods: We conducted a prospective cohort study enrolling patients with end-stage renal disease undergoing hemodialysis from local clinics and a medical center in Taipei. The serological markers of hepatitis B or C were checked annually for the new development of viral infection. We also collected patients prospectively for the management status of chronic hepatitis B or C patients.

Results: Overall, around 490 patients in hemodialysis centers were enrolled for the new development of HBV or HCV infection during 2014-2018. The incidence of HBsAg and anti-HCV positivity from seronegative patients was up to 0.67% (1 case) per year, respectively. We further collected 347 patients prospectively for detailed serological and virological tests. The prevalence of HBsAg and antiHCV positivity was 7% and 7%, respectively. In local hemodialysis clinics, about 10% patients were negative for both anti-HBc and anti-HBs; however, 82% of them were unwilling to receive self-paid HBV vaccination. Among HBsAg carriers with HBV DNA > 2000 IU/mL, 25% of them would like to receive antiviral therapy. About 59% of anti-HCV-positive patients had HCV viremia, but only

2020 消化系聯合學術演講年會

18% of them received direct antiviral agent (DAA) therapy.

In the medical center, 1% of patients had co-infection with HIV and 1% had dual HBV and HCV infection. The treatment rate was 40% for HBV-monoinfected patients, and 75% for HCV monoinfected patients. The rate of viral suppression or sustained virological response (SVR) by antiviral therapy against HBV or HCV was comparable to non-hemodialysis patients.

Conclusions: The incidence rate of acute HBV or HCV infection in patients on hemodialysis was less than 1% in Taipei. The prevalence of HBsAg carriage was lower, but anti-HCV positivity was higher than that in the general population. Only 18-25% of eligible patients on hemodialysis would like to receive HBV vaccination or antiviral therapy in the clinics. In contrast, more patients in the medical center received current standard of care.

㉗

中低劑量酒精加重非酒精性肝硬化大鼠的 血流動力異常 MEDIUM DOSE OF ALCOHOL INCREASES SEVERITY OF HYPERDYNAMIC CIRCULATION IN NON-ALCOHOLIC CIRRHOTIC RATS 1, 2

2, 3

1, 2

許劭榮 黃惠君 李發耀 侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學 3 臺北榮民總醫院內科部一般內科

1, 2

1, 2

黃怡翔

Background: Portal hypertension develops and aggravates during the progression of liver cirrhosis. There are several pathophysiological mechanisms of portal hypertension such as fibrogenesis, angiogenesis and change of intra- and extra-hepatic vascular contractility. Alcohol containing beverages have been widely distributed in human history and alcohol modulates the aforementioned actions and associated molecular pathways. Whether medium dose of alcohol that does not induce hepatic fibrosis in itself might worsen portal hypertension, however, is not known.

Aims: This study aimed to survey the relevant effects of medium dose of alcohol in rats with cholestatic liver cirrhosis and portal hypertension.

Meth od s : Choles tatic liver cirrhos is and po r t a l hypertension was induced in male Sprague-Dawley rats with bile duct ligation (BDL). Rats received sham or BDL operation were fed with ethanol (2.4 g/kg/day, oral gavage) or vehicle from the 8th to the 35th day after operations.

After that, portal hypertension-related parameters were evaluated.

Results: The results showed that chronic alcohol administration did not have effects on liver enzyme or fibrosis in sham or BDL rats. It suggested this dose of alcohol did not worsen liver cirrhosis. Interestingly, chronic alcohol administration decreased systemic vascular resistance and increased cardiac index in BDL rats. The plasma renin activity increased at the same time.

Alcohol increased splanchnic inflow. The mesenteric vascular density, protein expressions of iNOS, VEGF and p-VEGFR2 increased in alcohol-administered group. On the other hand, alcohol did not influence the splanchnic vascular contractility. In hepatic system, the hepatic fibrosis and vascular contractility were not affected by alcohol.

The liver iNOS protein expression increased in alcohol group. the collateral vascular contractility decreased in alcohol-treated group. After acute alcohol ingestion, the

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主題：脂肪肝相關疾病 collateral vasodilatation was found. The collateral vascular responsiveness also decreased after alcohol pre-incubation.

Conclusions: In conclusion, the net effects of medium dose of alcohol administration did not affect portal pressure.

However, the impacts on hemodynamic derangements and the increased mesenteric angiogenesis may worsen portal hypertension-related complications.

㉘

利用尿液脂肪酸結合蛋白和視黃醇結合蛋 白 -4 預測嚴重非酒精性脂肪肝病合併高血 壓病人的慢性腎臟性疾病進展 URINARY FATTY ACID AND RETINOL BINDING PROTEIN-4 PREDICT CKD PROGRESSION IN SEVERE NAFLD PATIENTS WITH HYPERTENSION 1

1,2

1,3

1,4

1,2

1,2

蔡友蓮 楊盈盈 劉志偉 黃祥芬 黃加璋 黃怡翔 1,2 1,2 林漢傑 侯明志 1 臺北榮民總醫院內科部 2 臺北榮民總醫院肝膽腸胃科 3 臺北榮民總醫院風濕免疫科 4 臺北榮民總醫院感染科

Background: High prevalence of chronic kidney disease (CKD) and hypertension had been reported among nonalcoholic fatty liver disease (NAFLD) patients. Detection of the CKD progression can begin early intervention to improve the prognosis of severe NAFLD. Serum and urine biomarkers including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), adhesion molecules, fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, had been reported to predict the CKD progression.

Aims: This bi-directional cross-sectional study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4) for the prediction of CKD progression in severe NAFLD patients with hypertension and proteinuria.

Methods: This study prospectively screened 330 severe NAFLD patients with abnormal liver and renal function tests from the medical records from October 2014 to March 2019. Then, 120 severe NAFLD patients met the inclusion criteria of hypertension and proteinuria (NAFLD+ HTN+). After excluding cases with excluding criteria, 90 severe NAFLD patients with hypertension and proteinuria (NAFLD+HTN+) were enrolled and divided into CKD (n=39) and non-CKD groups (n=51) according to the eGFR data within 24 months before time of inclusion. Finally, 39 NAFLD+ HTN+ patients with CKD were included for clinical serologic and urinary measurements.

Results: Among 39 NAFLD+HTN+ patients, 18 cases were categorized as CKD progression group according to the slope or reciprocal serum creatinine across 24 month before and 24 month after inclusion. Surrogate markers for hypertension, major risk factor for CKD, including

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serum CRP, sICAM-1, sVCAM-1 and urine VCAM-1 were significantly increased in CKD progression group.

FABP1, FABP4, RBP4 levels, both in serum and urine, were elevated in CKD progression group compared with CKD stable groups. In comparison with CKD stable group (n=21), the positive correlation between fold change values of hepatic fibrotic score (KPa), urinary FABP4 or urinary RBP4 versus severity of albuminuria were noted among CKD progression group. On multivariate analysis, high BMI (>25 kg/m2), high hepatic fibrosis score (>9.5KPa), high urinary level of VCAM-1 (>2239μg/g.cr), high urinary level of FABP4 (>115 ng/g.cr) and high urinary level of RBP4 (>33.5 mg/g.cr) are five independent predictors for progressive CKD during 24 months of follow-up. Among these five significant risk predictors of CKD progression, the increasing trend of odd ratio (3.2 or 4) for cases having more than any three or 4-5 risk factors as compared to reference group (with OR=1 for those with 0-2 risk factors) was found.

Conclusions: Through clinical approaches, this study revealed new five synergetic predictors including high BMI, hepatic fibrosis score, urinary level of VCAM-1, urinary level of FABP4 and RBP4, for the CKD progression in severe NAFLD patients with hypertension and proteinuria.

㉙

精瘦型與肥胖型非酒精脂肪肝病人之臨床 表現差異 - 多中心研究 THE DIFFERENCES IN CLINICAL MANIFESTATIONS BETWEEN LEAN AND OBESE NON-ALCOHOLIC FATTY LIVER DISEASE-A MULTI-CENTER STUDY 1

1, 5

2, 5

3, 5

4, 5

陳蕙芬 林志陵 黃奕文 楊勝舜 劉俊人 4, 5 4, 5 高嘉宏 陳培哲 1 臺北市立聯合醫院仁愛院區消化內科肝病中心 2 國泰綜合醫院肝臟中心 3 臺中榮民總醫院內科部胃腸肝膽科 4 國立臺灣大學附設醫院肝炎研究中心 5 臺灣肝臟疾病臨床試驗合作聯盟 Background: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. The global prevalence of NAFLD was estimated to be 15 to 30%. Metabolic comorbidities associated with a diagnosis of NAFLD included obesity, type 2 diabetes mellitus, hyperlipidemia, hypertension, and the metabolic syndrome.

The risk factors of NAFLD include male gender, aging, obesity, high serum levels of aminotransferase, triglycerides and total cholesterol. However, NAFLD can also occur in people with a normal body mass index, known as lean NAFLD. Aims: This study aimed to compare the anthropometric parameters, laboratory parameters and the severity of hepatic fibrosis by non-invasive examination between lean and obese NAFLD. Methods: This multi-center descriptive study recruited a total of 387 subjects with nonalcoholic fatty liver diseases detected by image findings from the Ren-Ai branch, Taipei City Hospital (TPECH-RA), National Taiwan University Hospital (NTUH), Cathay General Hospital (CGH) and Taichung Veterans General Hospital (VGHTC). The body mass index cutoff of 25 kg/m2 was used to divided cases into lean (BMI < 25 kg/m2) and obese (BMI ≧ 25kg/m2) NAFLD. The data of anthropometric parameters, laboratory tests, and liver fibrosis severity by non-invasive methods were collected. The differences in clinical manifestations between lean and obese non-alcoholic fatty liver disease were compared. Cases with chronic viral hepatitis were excluded.

Results: A total of 100 cases (25.8%) in the lean NAFLD group and 287 cases (74.2%) in the obese NAFLD group were enrolled. There was no significant difference in

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terms of sex, age, height, liver function, liver enzyme, the proportion of hypertension and diabetes mellitus, fasting glucose, total cholesterol level, and total triglyceride level between two groups. Compared with the obese NAFLD subjects, the lean NAFLD patients had less weight (64.0±8.5kg vs. 80.6±13.3kg, p<0.0001), less waistline (85.7±6.1cm vs. 97.4±9.3cm, p<0.0001), lower systolic blood pressure (131±16mmHg vs. 136±17 mmHg, p=0.024), lower serum creatine level (0.8±0.2 mg/dl vs.

0.9±0.2 mg/dl, p=0.008), and lower fasting insulin level (10.5±7.5 uIU/ml vs. 18.3±13.8 uIU/ml, p<0.0001).

Among these patients, 25 cases in the lean NAFLD group and 59 cases in the obese NAFLD group received transient elastography. Lean NAFLD patients had less CAP score, (280.6±56.5 dB/m vs. 327.6±39.7, p=0.001), but similar stiffness compared to the obese cases (8.3±7.3 vs 7.5±3.6, p=0.580). The NAFLD fibrosis score, FIB-4 and APRI between the two groups also showed no difference. The insulin resistance score (HOMA-IR) was estimated in 159 patients. The HOMA-IR had a positive correlation with BMI (0.283, p=0.003). The lean NAFLD group had significantly lower HOMA-IR than the obese NAFLD group.

Conclusions: Compared to the obese NAFLD patients, the lean NAFLD patients had lower CAP score and insulin resistance. However, the lean NAFLD group and the obese group have similar severity of fibrosis.

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台灣非酒精性脂肪肝的臨床與病理表現與 同時罹患慢性 B 的影響 PATHOLOGIC FINDINGS OF PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE AND THE IMPACT OF CONCURRENT HEPATITIS B VIRUS INFECTION IN TAIWAN 蘇浩俊 高嘉宏 曾岱宗 楊宏志 陳培哲 劉俊人 國立臺灣大學醫學院附設醫院內科部 國立臺灣大學醫學院附設醫院內科部臨床醫學與肝病 研究中心 Background: Pathologic data of non-alcoholic fatty liver disease (NAFLD) was limited and the association between NAFLD and chronic hepatitis B remained unclear in Taiwan.

Aims: This study aimed to determine the pathological manifestations of NAFLD and the impact of concurrent hepatitis B virus (HBV) infection in a medical center.

Methods: Retrospective review of 104 consecutive random liver biopsies with the histologic diagnosis of NAFLD or cryptogenic cirrhosis from 2009 to 2018 was conducted.

Clinical, biochemical and histological data were compared among various stages of NAFLD and between those with or without concurrent HBV infection.

Results: Advanced fibrosis was documented in 42% of Taiwanese patients with NAFLD according to METAVIR scoring system and was associated with elderly (odds ratio, 1.06; 95% CI, 1.03-1.10), hypertension (odds ratio, 2.97; 95% CI, 1.31-6.74), diabetes mellitus (odds ratio, 4.36; 95% CI, 1.78-10.70) and concurrent HBV infection (odds ratio, 3.55; 95% CI, 1.46-8.58) by multivariate analyses.

Concurrent HBV was found in 28.57% of NAFLD patients.

Patients with concurrent HBV had lower platelet counts, longer prothrombin time/INR and higher fibrosis stage than those without CHB. Conclusions: Advanced fibrosis in patients with NAFLD was related to aging, hypertension, diabetes mellitus and concurrent HBV infection. Concurrent HBV was associated with more severe liver diseases.

2020 消化系聯合學術演講年會

㉛

比較超音波的衰減圖像和纖維化檢測儀中 控制衰減參數之間的關係 - 一個新方法評估 非酒精性脂肪肝 COMPARING THE RELATIONSHIP BETWEEN ULTRASONIC ATTENUATION IMAGE (ATI) AND FIROSCAN’S CONTROLLED ATTENUATION PARAMETER (CAP)-A NEW METHOD FOR EVALUATING NONALCOHOLIC FATTY LIVER 伍麗莎 許柏格 蘇培元 陳洋源 徐有春 顏旭亨 蘇維文 彰化基督教醫院肝膽胃腸科 Background: As we know, Transient elastography (Fibroscan®) is a FDA approved non-invasive procedure to do liver stiffness measurement(LSM) and steatosis.

For steatosis, the degree of non-alcoholic fatty liver can be known through Fibroscan’s Controlled Attenuation Parameter (CAP). On the other hand, Attenuation imaging (ATI) is a new detection method that can quantify the degree of fatty liver. This device is installed on Aplio i800 (Toshiba Medical Systems). In this study, we compared whether there is a correlation between CAP and ATI among non-alcoholic fatty liver populations.

Aims: To see if there is a correlation between CAP and ATI among non-alcoholic fatty liver populations Methods: We retrospectively and randomly collected 27 patients in 1 year since January 1, 2019. These 27 nonalcoholic fatty liver patients were arranged Transient elastography (Fibroscan®) recorded with CAP (dB/m) and, at the same time, we also did ultrasound with ATI recording . Use pearson correlation by MedCalc Statistical Software version 19.1.3 (MedCalc Software bv, Ostend, Belgium) to check whether the reports are related.

Results: The average patient’s characteristic showed in table 1. We enrolled 27 patients: age: 51.3 ± 13.5 and BMI(Kg/m2): 29.4± 4.2 (mean ± SD ), the others are as follows in Table 1. We use pearson correlation for CAP (dB/m) and ATI showed excellent correlation ((Pearson’s r=0.613, 95% CI 0.304-0.805, p< 0.05).

Conclusions: Attenuation image (ATI) installed in ultrasound device showed in excellent correlation with CAP in Fibroscan device which is well known for evaluation of steatosis. In the future, it may be further applied to the screening of non-alcoholic fatty liver to benefit the population

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洋薊酸對肝細胞脂肪變性之作用 THE EFFECT OF CYNARIN ON STEATOSIS IN HEPATOCYTE IN VITRO 1,2

1,3

1,3

1,3

1,3

詹哲彰 李癸汌 侯明志 林漢傑 李發耀 1 臺北榮民總醫院內科部胃腸科 2 臺北榮民總醫院桃園分院內科部胃腸科 3 國立陽明大學醫學系

Background: Non-alcoholic fatty liver diseases (NAFLD) are wide spectrum diseases ranging from simple steatosis, steatohepatitis to liver cirrhosis. NAFLD currently has no proven effective treatment. Artichoke acid has liverprotective effect against a variety of liver toxins and has been found to reduce liver cholesterol and triglycerides.

Aims: The purpose of this study was to investigate whether the essential ingredients of artichoke extract, cynarin, had anti-steatosis effect on palmitic acid (PA)-treated hepatocytes in vitro.

Methods: A mouse hepatocyte cell line was used for the study and divided into (1) control (vehicle) group, (2) palmitic acid (PA) group, and (3) PA + cyanrin (1mg/ml) treatment groups. The effect of cynarin on the proliferation, the degree and the signaling pathway of steatotic hepatocyte were evaluated.

Results: PA treatment significantly induced steatosis and reduced proliferation in hepatocytes. Treatment with cynarin significantly decreased the degree of steatosis and did not affect the proliferation of steatotic hepatocytes. In steatotic hepatocytes, the gene expression of PPARa was significantly depressed. Cynarin treatment reversed the reduced expression of PPARa in steatotic hepatocytes.

Conclusions: Cynarin treatment could reduce steatosis and increase PPARa expression in PA-treated steatotic hepatocytes. This study suggested that cynarin may have potential benefit in the management of steatosis.

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主題：上消化道疾病（一）

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使用氫離子幫浦阻斷劑並沒有降低食道靜 脈曲張結紮術後死亡率 – 單一中心研究 PROTON PUMP INHIBITOR USE DID NOT LOWER THE MORTALITY RATE FOLLOWING ESOPHAGEAL VARICEAL LIGATION: A SINGLE CENTER EXPERIENCE 1

1

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張峻愷 郭行道 許銘仁 花逸茗 何宗翰 陳建安 1 奇美醫院胃腸肝膽科, 奇美醫院內科部 2 奇美醫院藥劑部 3 奇美醫院醫學研究部 4 奇美醫院全人醫療科

Background: Endoscopic variceal band ligation (EVL) is one of the effective procedure to control and prevent variceal bleeding in patients with liver cirrhosis, but it can be complicated by bleeding from post-EVL ulcers. Several studies have reported that proton pump inhibitors (PPI) decrease the size of post-EVL ulcers. However, evidence are limited as to whether PPIs actually reduce the risk of bleeding or lower the mortality after EVL. Aims: To determine whether PPI causes post-ligation bleeding and mortality reduction effect in EVL within 30 days.

Methods: We retrospectively evaluated patients that underwent emergent or prophylactic EVL from June 2018 to December 2018 in Chi-Mei Medical Center.

Results: A total 112 patients meet the inclusion and the exclusion criteria were enrolled. 102 patients have received PPI and 10 patients were in the group that without PPI use.

27.5% (N=28) patients have post-EVL bleeding within 30day in the group of “Use PPI” and none of the patient have post-EVL bleeding within 30-day in the “Non-use PPI” group. There is no significant difference to mortality in 30 days after EVL between the “Use PPI” and “Non-use PPI” groups (7.8% vs. 10%).

Conclusions: In conclusion, post-EVL PPI use does not show better outcomes in post-EVL 30-day bleeding and mortality rate compared to the patients without PPI use.

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運用高解析度食道壓力檢查探討胃食道逆 流症合併食道無效性蠕動與二度收縮之關 聯性 EVALUATE THE INTERRELATIONSHIP BETWEEN INEFFECTIVE ESOPHAGEAL MOTILITY AND SECONDARY PERISTALSIS IN GERD: STUDIES WITH HIGH RESOLUTION MANOMETRY 1

2

1

1

1

1

雷尉毅 王仁宏 易志勳 劉作財 洪睿勝 翁銘彣 1 1 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃 1 科 2 佛教慈濟醫療財團法人花蓮慈濟醫院醫學研究部 Background: Secondary peristalsis, triggered by esophageal distension, contributes to the clearance of retained refluxate from the esophagus. Ineffective esophageal motility (IEM), common found in gastroesophageal reflux disease (GERD), is usually associated with impaired secondary peristalsis. Data were scanty regarding characterizing peristaltic physiology of distension-induced secondary peristalsis by high resolution manometry (HRM).

Aims: The aim of this study was to investigate the hypothesis whether there is a difference in secondary peristalsis among subgroups of GERD patients with and without IEM, and healthy adults.

Methods: We prospectively enrolled 28 consecutive patients (49.7±11.0 years, 10 male) presenting for evaluation of GERD symptoms. Seventeen healthy volunteers (30.2±6.4 years, 15 male) without GERD symptoms were also enrolled. Esophageal HRM with a catheter containing one air-injection in mid-esophagus was performed for all participants. The secondary peristalsis was stimulated by rapid mid-esophageal injections of 20 mL air. Esophageal peristaltic performance was evaluated using distal contractile integral (DCI). We compared HRM parameters of secondary peristalsis including DCI, 4-second integrated relaxation pressure (IRP-4s) and distal latency (DL), as well as the response and effective rate of triggering secondary peristalsis between healthy adults, patient with normal peristalsis and IEM. Results: On standard HRM, 16 patients (57%) had IEM and the remaining 12 had normal manometry. IEM patients had significantly lower DCI values and increased swallows with peristaltic breaks, compared to patients with normal

2020 消化系聯合學術演講年會

peristalsis and normal adults (p < 0.001). By triggering of secondary peristalsis, normal adults had significantly higher IRP-4s (p = 0.003), higher DL (p < 0.001) and higher DCI values (p < 0.001), compared to patients with normal peristalsis and IEM. The secondary peristalsis was triggered more frequently in normal adults than patients with normal peristalsis (69.4% vs. 24.2%, p < 0.001) and IEM (69.4% vs. 21.9%, p < 0.001). The effective contraction rate which determined as DCI > 450mmHg.sec.cm was also higher in normal adults (36.5%) patients with normal peristalsis (36.5% vs. 19.4%, p < 0.001) and IEM (36.5% vs. 6.3%, p < 0.001). There was no difference in the triggering or effective rate between patients with and without IEM. Conclusions: On standard HRM, 16 patients (57%) had IEM and the remaining 12 had normal manometry. IEM patients had significantly lower DCI values and increased swallows with peristaltic breaks, compared to patients with normal peristalsis and normal adults (p < 0.001).

By triggering of secondary peristalsis, normal adults had significantly higher IRP-4s (p = 0.003), higher DL (p < 0.001) and higher DCI values (p < 0.001), compared to patients with normal peristalsis and IEM. The secondary peristalsis was triggered more frequently in normal adults than patients with normal peristalsis (69.4% vs. 24.2%, p < 0.001) and IEM (69.4% vs. 21.9%, p < 0.001). The effective contraction rate which determined as DCI > 450mmHg.sec.cm was also higher in normal adults (36.5%) patients with normal peristalsis (36.5% vs. 19.4%, p < 0.001) and IEM (36.5% vs. 6.3%, p < 0.001). There was no difference in the triggering or effective rate between patients with and without IEM.

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胃食道逆流症患者之食道微生物菌相特徵 在食道無效蠕動的意義 ESOPHAGEAL MICROBIOME SIGNATURES IN GERD PATIENTS: IMPLICATION FOR INEFFECTIVE ESOPHAGEAL MOTILITY 1

2

2

1

2

1

翁銘彣 吳偉愷 劉勃佑 雷尉毅 吳明賢 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃 1 科 2 臺大醫院胃腸肝膽科 Background: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) associated with varied severity in esophageal dysmotility. To date, the microbiome community in IEM and its link to the severity in esophageal motility has not been well investigated.

Aims: We aimed to investigate the hypothesis whether there is difference in microbiome community between patients with and without IEM. Methods: Thirty-seven patients with symptomatic GERD had undertaken high-resolution manometry (HRM) with multiple rapid swallows test (contraction reserve).

Esophageal mucosal tissues were acquired through biopsies by upper endoscope. Bacterial DNA were extracted from esophagus tissues and 16S rRNA gene were amplified for next generation sequencing. A state-of-the-art analytical pipeline QIIME2 in tandem with the expanded Human Oral Microbiome Database (eHOMD) was used to analyze the sequencing data. All participated patients had signed a waiver of informed consent.

Results: Among the 37 esophageal biopsy samples, 7583 microbiome amplicon sequence variant (ASV) features were identified, and were annotated to 325 species/strain, 106 genera, 54 families, and 11 phyla.

The genus of Streptococcus, Prevotella, Veillonella, Nisseria, Fusobacterium, Haemophilus, Leptotrichia, and Porphyromonas were most commonly found in these GERD patients. The global microbiome profiles between normal motility and IEM were similar, however, some bacteria were found to be enriched in IEM with reserved contraction group, probably indicating their roles in the pathogenesis of IEM. As we compared microbiome between reserved vs non-reserved esophageal contraction groups, a significant difference was noted to show that some bacteria were remarkably decreased in non-reserved group. Notably, a ubiquitous bacterial phylum in human

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oral flora, Saccharibacteria (TM7), was found to be remarkably reduced in IEM with non-reserved contraction group, which may serve as a functional biomarker for abnormal esophageal contraction. A microbiome-based random forest model was built to predict non-reserved contraction and yielded an AUROC = 0.94 (0.87-1). Taken together, we found distinct microbiome features between normal esophageal motility versus IEM and between normal versus non-reserved esophageal function.

Conclusions: We firstly demonstrated distinct microbiome features in reflux patients with IEM. These data may provide mechanistical insights into pathophysiological evidence of esophageal hypomotility and facilitate our understanding about the relationship between the human microbiome and esophageal dysmotility.

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糜爛性食道炎的盛行率和嚴重程度在腹腔 鏡胃縮小手術術後 1 年明顯增加 THE PREVALENCE AND SEVERITY OF EROSIVE ESOPHAGITIS SIGNIFICANTLY INCREASED 1 YEAR AFTER LAPAROSCOPIC SLEEVE GASTRECTOMY 1,2,3

3,4

3, 5

3,4

1,3

蔡英楠 戴啟明 陳建翰 王文 曾政豪 6,7,8 郭昭宏 1 義大癌治療醫院內科部 2 高雄醫學大學臨床醫學研究所 3 義守大學 4 義大醫院內科部 5 義大醫院外科部 6 高雄醫學大學附設中和紀念醫院胃腸內科 7 高雄醫學大學 8 高雄市立小港醫院

Background: Laparoscopic sleeve gastrectomy (LSG) is a popular bariatric surgery in many countries and several studies showed an increase in the incidence of clinical gastroesophageal reflux (GERD) by clinical questionnaires.

Aims: We objectively evaluated the incidence and change of erosive esophagitis (EE) 1 year after LSG. Methods: The data of patients underwent LSG between February 2007 and March 2016 at E-Da hospital were retrospectively reviewed. Exclusion criteria included patients with major surgical complications or conversion to laparoscopic Roux-en-Y gastric bypass after LSG. The endoscopic findings, demographic and anthropometric data before and 1 year after LSG were recorded. The severity of EE was assessed according to the Los Angeles (LA) classification.

Results: A total of 316 patients were included and the median follow up time was 13 months (range, 12–23). The prevalence and severity of EE increased significantly after LSG. Before LSG, 96 patients (30.4%) were found to have EE, and all cases were grade A and B. After surgery, 215 patients (68%) had EE, including 136 (43%) with grade A, 62 (19.6%) with grade B, and 17(5.4%) with grade C and D. Patients were also divided into no change or reduced severity of EE (n=150) and increased severity of EE (n =166). In the group of increased severity of EE, 127 patients (76.5%) were de novo EE after LSG. Conclusions: The prevalence and severity of EE increased significantly 1 year after LSG. Patients with de novo EE account for 76.5% of patients with increased severity of EE after LSG.

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㊲

㊳

易志勳 劉作財 洪睿勝 雷尉毅 翁銘彣 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃 科

吳忠翰 陳建誠 洪明原 康瑞文 郭欣瑜 黃千睿 1, 2 莊喬雄 1 國立成功大學醫學院附設醫院內科部 2 國立成功大學前瞻醫療器材科技中心 3 國立成功大學醫學院附設醫院急診部

探討食道收縮生理對內視鏡正常逆流症患 者其逆流酸負載之影響 IMPACT OF ESOPHAGEAL PERISTALTIC PHYSIOLOGY TO ESOPHAGEAL REFLUX BURDEN IN GERD PATIENTS WHO HAVE NORMAL ENDOSCOPY

Background: A majority of patients with gastroeophageal reflux disease (GERD) have normal endoscopy (NE).

Patients without NE have greater acid exposure, while heterogeneity in acid reflux parameters is found in patients with normal endoscopy. Association between ineffective esophageal motility (IEM) and increased acid burden is evident in patients with GERD. However, those findings are rarely reported in patients with normal endoscope.

Aims: Our study aimed to investigate the hypothesis whether esophageal primary or secondary peristalsis has any influence on esophageal reflux parameters in patients with NE. Methods: We enrolled consecutive PPI-naïve patients with typical reflux symptoms and NE in a single medical center.

All patients had undertaken HRM and 24-h impedancepH studies. By HRM, secondary peristalsis was performed with 10 times of 20-mL rapid air injections, while primary peristalsis was done with 10 times of 5-mL wet swallows.

Results: A total of 29 patients had completed the studies, of whom IEM were found in 17 NE patients. There was no difference in any of reflux phenotypes between patients with and without IEM (p = 0.29). All of reflux parameters from 24-h impedance-pH were comparable between patients with and without IEM (p = NS). Normal secondary peristalsis was observed in 22 patients. Patients with and without normal secondary peristalsis had similar findings in terms of reflux phenotypes or any variable of reflux parameters (p = NS).

Conclusions: Our work has shown that esophageal primary or secondary peristalsis has no obvious impact on esophageal reflux burden as determined by 24-h impedance-pH in NE patients. Our study indicates that neither IEM nor impaired esophageal secondary peristalsis has pathophysiological role in esophageal reflux burden, especially for reflux patients who have normal endoscopy.

上消化道再出血即時監測系統 A NOVEL UPPER GASTROINTESTINAL MONITORING SYSTEM TO TRACK UPPER GASTROINTESTINAL BLEEDING: A PILOT STUDY 1

2

3

1

1

1

Background: Second-look endoscopy would be scheduled, if rebleeding is suspected after primary endoscopic hemostasis of upper gastrointestinal (UGI) bleeding.

However, the routine second-look endoscopy is a high-cost intervention and could even increase unnecessary risk.

Aims: We aimed to develop a novel continuous UGI monitoring system to improve the tracking of UGI bleeding.

Methods: The UGI monitoring system consisted of a tiny and thin tube camera, a wearable host device, and a mobile display device. The tube camera was connected to the host device and then inserted into stomach via nasal tunnel. The host device was set to acquire images every minute and sent the images to the mobile device, in which an image analysis application was installed for rebleeding detection.

Patients with Rockall scores ≥ 3 were eligible for this study.

The UGI monitoring system was placed on patients by the trained medical staff. The monitoring period was ≤ 3 days because most rebleeding events occurred within 3 days.

The comfort level was scaled from 0 to 5 by the patients.

Results: Fourteen patients who had UGI bleeding and received primary endoscopy hemostasis were included in this study (age 66.2 ± 13.5, 3 females, Rockall score 3-9) and the trial is still ongoing. From the images, how the contents inside the stomach changed over time was observed. Coffee-ground substances, blood clots, red blood, and food contents were photographed. Up to date, the included patients had no rebleeding event during the system monitoring. However, this system could confirm no active bleeding in stomach 1-4 days earlier than observation for the disappearance of melena. Moreover, the comfort level of using the UGI monitoring system was less than 2.12 in average.

Conclusions: This UGI monitoring system could confirm no active gastric bleeding earlier. It has a potential to evaluate various scenarios in the UGI tract with an endurable comfort level.

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2020 消化系聯合學術演講年會

主題：下消化道疾病

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年齡性別校正之全大腸鏡腺瘤息肉偵測率 可用以預測大腸鏡術後發生大腸直腸癌之 風險 AGE-GENDER ADJUSTED TOTAL COLONOSCOPY ADENOMA DETECTION RATE IS APPLICABLE ON THE RISK STRATIFICATION OF POST COLONOSCOPY COLORECTAL CANCER 1

1,2

1,2

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1

陳奕成 吳明順 粟發滿 連吉時 劉佩嘉 1 臺北市立萬芳醫院消化內科 2 臺北醫學大學醫學系

Background: Adenoma detection rate (ADR) is an important quality indicator of colonoscopy and it reflects adequate inspection of the bowel mucosa by an endoscopist.

Low ADR is well known to be linked to the increased risk of development of post colonoscopy colorectal cancer (PCCRC). To fulfill the principle ADR definition (age >= 50 years old, first screening colonoscopy), the calculation of ADR become complex when several exclusion criteria are applied. A new simple ADR calculation method may bring more convenience to routine colonoscopy quality monitoring.

Aims: The purpose of this study is to evaluate whether agegender adjusted total colonoscopy ADR is applicable on the PCCRC risk stratification Methods: A retrospective cohort was conducted. Total colonoscopies (including screening, surveillance, diagnostic, and therapeutic) were matched with their resected or biopsied tissue specimen via pathology database. Positive adenoma detection is defined by pathological confirmation of colonic adenomatous neoplasia (including adenomatous polyp, tubular adenoma, tubulovillous adenoma, villous adenoma, sessile serrated adenoma, traditional serrated adenoma, dysplasia, and adenocarcinoma). Total colonoscopy ADRs of each endoscopist were calculated after age and gender adjustments (age >= 50 years old, and each sex category holds equal weights). Finally, the age-gender adjusted total colonoscopy ADR was subdivided into 3 groups (<30%, 30-40%, >40%) for correlation of PCCRC incidence.

Results: From 2007/1/1 till 2018/12/31, total 46368 patients receiving 61596 times of colonoscopies by 26 endoscopists. 1796 patients were diagnosed with CRC from stage I to IV. According to 2018 World Endoscopy Organization Consensus Statements on PCCRC and post

82

image CRC (PICRC), 66 patients are defined as PCCRC within 5 years after index colonoscopy (PCCRC-5y, type I+A 34 cases; type B 20 cases; type C 12 cases). The remainder 1730 patients are classified as detected CRC. The incidence of PCCRC type I+A is inversely correlated with total colonoscopy ADR (0.0568% for ADR>40%, 0.0939 for ADR 30-40%, 0.1518% for ADR<30%), whereas the incidence of PCCRC type B or type C has no correlation with total colonoscopy ADR throughout the 3 ADR groups.

Conclusions: Age-gender adjusted total colonoscopy ADR is inversely correlated with PCCRC-5y type I+A. It is simple to calculate and might be useful for routine colonoscopy quality monitoring.

2020 消化系聯合學術演講年會

㊵

使用機器學習於大腸內視鏡影像結合人工 特徵與機器特徵判別息肉惡性程度 USING COLORECTAL ENDOSCOPIC IMAGES IN MACHINE LEARNING COMBINED WITH ARTIFICIAL FEATURES AND NON-ARTIFICIAL FEATURES TO DETERMINE THE DEGREE OF POLYPS 1

1,2

1

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machine features can obtain higher accuracy than artificial features. If artificial features are combined with machine features, the results we get are not ideal. It can be seen that the addition of machine features can cause confusion and reduce accuracy.

2

葉宇軒 葉欣榮 羅崇銘 陳俊璋 唐瑞祥 張君照 1 臺北醫學大學醫學科技學院醫學資訊所 2 臺北醫學大學附設醫院消化內科

Background: Colorectal cancer is the third leading cause of cancer death. Malignant colorectal polyps can develop into colorectal cancer. The sooner a gastroenterologist detects a malignant colon polyp, the better the patient’s prognosis.

Aims: This study hopes to quickly identify polyp types from colonoscopy images through image feature analysis combined with machine learning.

Methods: In machine learning, we use artificial feature extraction to build the classification model, and also use deep learning among non-artificial features to compare the difference between the two models. Our images were obtained from the clinical data of patients with gastroenterology in the Department of Gastroenterology, Taipei Medical University. There were 1991 images, including 1053 hyperplastic polyps, 938 adenomatous polyps and adenocarcinomas.

Results: We use the artificial eigenvalue Gabor with 21 machine learning algorithms, of which Ensemble Subspace KNN has 93.2% with the highest accuracy. In the deep learning of machine features, we achieved a higher accuracy rate, and achieved a higher accuracy rate of 98.4% in Resnet-101. However, when combining artificial features GLCM and Gabor for machine learning, the accuracy rate actually decreases. The highest accuracy rate in the Alexnet part is 66.5%, the highest in the Inception-V3 part is 66.6%, and the highest in the Resnet-101 part is 72.7%.

Conclusions: According to the research results, we use many methods to train some models that are effective for the identification of colon polyps. In addition, we also find that the artificial features and machine features are indeed slightly different. When the amount of training data is not large, the artificial feature analysis method is used to obtain similar accuracy compared to the machine feature. However, when the amount of data is large,

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㊶

大腸直腸癌患者糞便中差異表現基因的分 子意義：癌症復發及其易受的化學療法 MOLECULAR SIGNIFICANCE OF DIFFERENTIALLY EXPRESSED GENES IN FECES OF PATIENTS WITH COLORECTAL CANCERS: CANCER RECURRENCE AND ITS SUSCEPTIBLE CHEMOTHERAPY 1,2,4,5

3,4

1,6

黃紀榕 李嘉龍 張君照 1 臺北醫學大學附設醫院消化內科 2 國泰綜合醫院醫學研究部臨床醫學研究中心 3 國泰綜合醫院內科部腸胃內科 4 輔仁大學醫學院 5 國防醫學院生物化學研究所 6 臺北醫學大學醫學院 Background: Colorectal cancer (CRC) is considered to develop slowly via a progressive accumulation of genetic mutations. CRC relapse markedly decreases the 5-year survival of patients following surgery. The messenger (m) RNA molecules that are present in human feces faithfully represent CRC manifestations.

Aims: We hypothesize that genes involved in CRC relapse may serve as prognostic indicators and could be quantified in human feces.

Methods: Genes in the feces of recurrent CRC patients were evaluated by comparing with patients without recurrence. Clinical tissues, cell and animal models were used to clarify the roles of target gene in chemotherapeutic efficacy, CRC tumorigenesis, invasion, and migration.

Results: The growth arrest-specific 2 (GAS2) and placentaspecific 8 (PLAC8) were differentially expressed in the feces of CRC patients. These two genes were found to be linked to potential cancer relapse through the primary SW480 cell line and its lymph node metastatic derivative (SW620 cell line). In our in vitro studies, the overexpressed GAS2 or PLAC8 was associated with cellular growth and migration, cell cycle regulation, and with chemotherapeutic sensitivity. We further found that the cell division of GAS2-overexpressed CRC cells could be impaired by treating cells with XK469 (NSC 697887). The PLAC8 was nucleated at the centrosome during mitosis and dynamically regulated in mitotic cells. The tumorigenic and invasive effects of PLAC8 on CRC cells were also confirmed in a xenograft mouse model.

Conclusions: Our findings suggest that genes in feces can faithfully reflect the status of CRC. Either GAS2 or PLAC8

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may have potential clinical applications for predicting early CRC relapse after radical resection. Agents manipulating the cell division or mitosis may control CRC relapse. This will help in selecting the best therapeutic option for patients overexpressing GAS2 or PLAC8 in CRC cells. Our results comprehensively suggest that genes in feces may be a chemotherapeutic reference, especially the differentially expressed genes for CRC progression or relapse.

2020 消化系聯合學術演講年會

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比較換水大腸鏡與二氧化碳灌氣大腸鏡對 右側大腸腺瘤型息肉漏檢率的影響：一項使 用帽蓋輔助同日進行兩次右側大腸檢查的 前瞻性隨機分組試驗 COMPARISON OF RIGHT COLON ADENOMA MISS RATES BETWEEM WATER EXCHANGE AND CARBON DIOXIDE INSUFFLATION: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL WITH CAPASSISTED COLONOSCOPY 1

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鄭吉良 蘇怡佳 郭彥麟 謝毓錫 唐瑞祥 4 Felix W. Leung 1 中壢長榮醫院胃腸科 2 臺北醫學大學附設醫院胃腸肝膽科 3 嘉義大林慈濟醫院胃腸肝膽科 4 美國加州大學洛杉磯分校醫學院

(OR, 0.47; 95% CI, 0.23-0.94). Compared with cCO 2 group, cWE also significantly decreased serrated polyp miss rate in the right colon (17.4% vs. 39.3%, P = 0.0017).

The inspection times during overall withdrawal (17.3 ± 5.2 vs. 17.4 ± 4.7 min, P = 0.80) and during the first and tandem examinations of the right colon (6.6 ± 2.0 vs. 6.1 ± 2.4 min [first], P = 0.08; 5.2 ± 1.8 vs. 5.4 ± 1.8 min [tandem], P = 0.30) were similar. cWE maneuvers directed at near-complete removal netted 98% of infused water upon arrival to the cecum confirming the appropriate application of WE. Conclusions: Compared with cCO2 insufflation, cWE with near-complete removal of infused water during insertion significantly decreased AMR in the right colon. The data support the potential utility of WE in preventing PCCRC and justify its inclusion in CRC prevention programs.

Background: Previous studies showed adenoma miss rates (AMR) of 34-39% in the right colon. Missed lesions contributed to postcolonoscopy colorectal cancer (PCCRC).

We performed a prospective randomized controlled trial (RCT) with cap-assisted water exchange (cWE) and capassisted CO 2 insufflation (cCO 2) to determine whether cWE with near-complete removal of infused water during insertion could reduce the AMR in the right colon.

Aims: The primary outcome was right colon AMR. Methods: From April to October 2019, consecutive patients aged ≥45 years undergoing colonoscopy were randomized 1:1 to receive cWE or cCO2 insufflation during insertion.

Withdrawal was performed with CO2 insufflation in both groups. A tandem right colon examination was performed by a blinded endoscopist. Miss rates were calculated as the number of additional adenomas/polyps detected during the tandem examination divided by the total number of each detected in both examinations.

Results: A total of 262 patients were enrolled in the intention-to-treat analysis. The baseline demographics and procedure indications were comparable. Compared with cCO2 group, cWE significantly decreased AMR (18.0% vs. 34.6%, P = 0.0025) in the right colon. In a multivariate logistic regression, patients with two or more adenomas in the right colon at the index examination were more likely than patients with no or one adenoma detected at the index examination to have missed adenoma (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.29-5.13). A protective effect against right colon AMR was demonstrated for cWE

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㊸

「大腸鏡檢查未罹癌後，三年内發生之結直 腸癌」其特性與根本原因分析 POST-COLONOSCOPY COLORECTAL CANCER (PCCRC-3Y) DETECTED IN A SINGLE HOSPITAL - CLINICAL FEATURES AND ROOT-CAUSE ANALYSIS 1

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黃興強 張允亮 張鴻俊 張麗文 劉玉華 孫灼基 1 1,2 楊國卿 林裕民 1 新光吳火獅紀念醫院胃腸肝膽科 2 輔仁大學醫學系

Background: Post-Colonoscopy Colorectal Cancer (PCCRC) is closely related to the quality of colonoscopy.

Understanding the features of PCCRC are important for quality improvement.

Aims: This study aimed to evaluate the clinical presentations and causes of PCCRC in a single hospital.

Methods: We retrospectively evaluated colorectal cancers reported in a single hospital between July 2016 and November 2019 from the endoscopy reporting system and cancer registry database. PCCRC-3y is defined as follows: CRC that had been diagnosed 6 to 36 months after initial colonoscopy, when no cancer had been detected.

We reviewed history of every case of PCCRC in detail.

The PCCRC-3y rate, age gender, cancer stage (determined

by AJCC 8th Edition) and the most plausible cause were analyzed.

Results: A total of 600 CRCs were reported in the endoscopy reporting system and cancer registry database between July 2016 and November 2019.

There were 26 PCCRCs (4.3%) identified in this period.

Among them, 19 cases meet the criteria of PCCRC-3y.

The rate of PCCRC-3y was 3.2%. The median age was 71 years old. The male to female ratio was 13:6. The median time to PCCRC-3y was 590 days. The stage 0, 1, 2, 3 and 4 of PCCRC-3y were 12.5%, 37.5%, 31.2%, 12.5% and 6.3% respectively. Possible explanations of PCCRC were missed lesions (84.2%, n=16), incomplete removal of polyps (5.2%, n=1) and deviation from planned management pathway (10.5%, n=2) at index colonoscopy.

Conclusions: PCCRCs are not rare events in our clinical practice. Though more than 80% of were identified at localized stages (stage 0,1 and 2); only 10% of PCCRCs were suitable for colonoscopy treatment. In similar with previous reports, “Missed lesions” at index colonoscopy is the most possible explanation of PCCRC. These results suggest a significant number of PCCRCs are avoidable with the improvement the quality of coloscopy.

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水下內視鏡粘膜切除術在切除大腸直腸腫 瘤的應用：單一醫學中心的經驗 UNDERWATER ENDOSCOPIC MUCOSAL RESECTION FOR COLORECTAL NEOPLASM: A SINGLECENTER EXPERIENCE 鍾秉軒 康瑞文 陳柏潤 莊喬雄 陳炯瑜 成大醫院內科部 Background: Endoscopic mucosal resection (EMR) with submucosal injection is a standard method to resect larger colorectal polyps. Underwater endoscopic mucosa resection (UEMR) without submucosal injection has emerged as an alternative method for removing large or flat colorectal polyps.

Aims: To assess the clinical outcomes of patients receiving UEMR Methods: This is a retrospective, single-center study. We enrolled patients who had colorectal polyps sized larger than 1 cm and received UEMR, and analyzed the clinical effectiveness and safety.

Results: A total of 94 colorectal polyps, contributed by 85 patients with a mean age of 65.4 year-old (39-90), removed

by UEMR were included. Fifty-one polyps (54.3%) were located at the proximal colon. The average size of the polyps was 14.9 mm (10-35 mm). Histologically, 76 (80.9%) of the lesions were adenomas, 8 (8.5%) were serrated adenomas or hyperplastic polyps, 5 (5.3%) were adenomas with moderate to high-grade dysplasia, or carcinoma in situ, and 5 (5.3%) were adenocarcinomas with submucosal invasion. Overall en bloc resection rate was 75.5%, and the en bloc resection rate was lower for polyps ≥ 2 cm than for polyps < 2 cm (34.8% vs. 88.7%, p<0.001). En bloc resection rate was also higher in lesions without prior endoscopic manipulation (82% vs. 33%, p<0.001). For safety, intraprocedural bleeding requiring endoscopic hemostasis occurred in 25 cases and were more frequent in cases with polyps ≥ 2 cm (47.8% vs. 19.3%, p<0.01). One patient had perforation (1.1%) and treated by endoscopic closure without surgical intervention. There was no significant difference in complication rates between lesions with or without prior endoscopic manipulation. No delayed complications, including perforation or bleeding, were reported.

Conclusions: UEMR is a safe method for endoscopic resection of larger colon polyps with or without prior manipulation. More efforts should be made to improve the en bloc resection rate in polyps larger than 2 cm.

2020 消化系聯合學術演講年會

主題：膽胰疾病（一）

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經皮或經內視鏡膽道引流術於可切除的肝 門膽管癌之術後死亡率：系統性回顧和統合 分析 POSTOPERATIVE MORTALITY OF PRECUTANEOUS VERSUS ENDOSCOPIC BILIARY DRAINAGE IN RESECTABLE HILAR CHOLANGIOCARCINOMA: SYSTEMIC REVIEW AND META-ANALYSIS 1

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方華珍 鄭勝偉 吳明順 1 萬芳醫院消化內科 2 臺北醫學大學醫學院醫學系 Background: Percutaneous biliary drainage (PBD) and endoscopic biliary drainage(EBD) are the preoperative procedures performed to relieve obstructive jaundicerelated complications and reduce postoperative liver remnant failure rate . However, studies have shown contradictory results that PBD has negative impact on the survival rate of patients with resectable hilar cholangiocarcinoma.

Aims: Our purpose was to pool all the studies , and compare the postoperative mortality and other adverse e ff e c t s o f P B D v e r s u s E B D f o r r e s e c t a b l e h i l a r cholangiocarcinoma. So we could find out which one could be the first line of preoperative biliary drainage.

Methods: We searched through PubMed, Cochrane/ CENTRAL, EMBASE, Scopus and CNKI and included both randomized and nonrandomized studies in our metaanalysis. We used RevMan 5.3 for our meta-analysis.

Results: 12 studies were eligible for our meta-analysis.

In our study, PBD has significantly higher postoperative mortality than EBD 27 of 247 (10.9%) versus 14 of 280(5%); odds ratio [OR], 0.42; 95% confidence interval[CI], 0.21-0.86; P value=0.02. Other outcomes like liver abscess, intra-abdominal abscess, cholecystitis, bleeding, sepsis, wound infection, postoperative morbidity, tube dislocation and blockage, there is no statistically significant difference between PBD and EBD. Conclusions: Our meta-analysis has shown PBD shortens the postoperative survival duration of resectable hilar cholangiocarcinoma cases. We suggest EBD as the first preoperative biliary drainage method, PBD as the second choice if EBD fails at the initial attempt.

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針對惡性膽道阻塞需置放金屬支架病人，使 用內視鏡逆行性與經皮下前行性兩種方式 的併發症之比較 COMPARISON OF COMPLICATION AFTER METALLIC STENTING FOR MALIGNANT BILIARY OBSTRUCTION BETWEEN ENDOSCOPIC RETROGRADE AND PERCUTANEOUS TRANSHEPATIC ANTEGRADE ROUTES 1

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詹易達 蔡明宏 郭雨庭 蘇浩俊 黃永輝 廖偉智 1 王秀伯 1 臺大醫院內科部 2 臺大醫院新竹分院內科部

1

Background: Malignant tumors may cause a variety of complications including malignant biliary obstruction related jaundice. The symptoms of obstructive jaundice such as pruritus, nausea, loss of appetite, fever, delayed wound healing, decrease patient’s quality of life significantly. Relieving malignant biliary obstruction not only improves patient’s quality of life but also decreases medical cost. Currently, both endoscopic retrograde and percutaneous antegrade biliary drainage could achieve high successful rates and maintain longer duration. But few studies compare the complication of the two methods.

Aims: The aim of this study is to compare the complication of the two methods, including infection, stent migration, stent occlusion, pancreatitis, cholecystitis, etc.

Methods: This study is a retrospective study and enrolls the patients with malignant biliary obstruction receiving endoscopic retrograde or percutaneous antegrade biliary metallic stenting at National Taiwan University Hospital between January 2011 to December 2015.

The clinicopathological features and procedure-related complications, including infection, bleeding, perforation, pancreatitis, cholecystitis, etc, of the two method was compared.

Results: Total 104 patients of percutaneous antegrade group and 86 patients of endoscopic retrograde group were enrolled respectively. No statistically significant difference was found between the two groups in overall stent dysfunction (antegrade vs retrograde group; 30.8% vs 22.1%, p=0.0514). Stent-related pancreatitis rate is higher in retrograde group (antegrade vs retrograde group; 1% vs 9.3%, p=0.0119). Procedure-related bleeding event is higher in antegrade group (antegrade vs retrograde group; 7.7% vs 1.2%, p=0.0421). The proportion of post-

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procedure cholangitis is lower in retrograde group, though not statistically significant (antegrade vs retrograde group; 21.2% vs 12.8%, p=0.1299).

Conclusions: Metallic stenting is an effective method for alleviation of malignant biliary obstruction, either through antegrade or retrograde route. No significant difference between antegrade and retrograde group regarding to stent patency. Less stent-related pancreatitis in antegrade group and less bleeding event in retrograde group.

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機器學習計算機輔助腹部超波檢查於膽結 石和膽囊炎 IDENTIFICATION OF CHOLELITHIASIS AND CHOLECYSTITIS BY MACHINE LEARNING COMPUTER-ASSISTED ABDOMINAL ULTRASOUND EXAMINATION. 游之瑞 張君照 臺北醫學大學附設醫院內科部消化內科 Background: The goal of this study is to make the computer machine learning system to identify some abdominal ultrasound pictures. We hope that the computer will learn to identify gallstones and cholecystitis from the ultrasound images taken by physicians or technicians and make a preliminary diagnosis.

Aims: We utilized convolutional neural networks (CNNs) and abdominal ultrasound image to detect gallstone and cholecystitis.

Methods: According to the database of the Department of Gastrointestinal Ultrasound Image Database of Taipei Medical University Hospital and over 23,500 abdominal ultrasound images, we exclude poor resolution pictures.

The definition of cholecystitis is based on abdominal ultrasonographic diagnosis by physicians. For gallstone detection, we use object detection technology to detect stone object by Single Shot MultiBox Detector (SDD) Feature Pyramid Network (FPN) neural network which base on ResNet50 and manually annotate objects on the ultrasound image, including area size of gallbladder, area size of gallstone, number of gallstone as the network input data.

For cholecystitis detection, we use object classification technology to detect symptoms by MobileNet V2 neural network and manually annotate objects on ultrasound image including thickened gallbladder wall as the network input data.

Results: On gallstone detection, by well-tuned SSD FPN neural network based on ResNet-50, the model achieves 86.86% AP and 84.69% Recall on 14,000 ultrasound image at 47.6 FPS on GPU (Nvidia GeFroce GTX 1080 Ti 11GB).

For the version replace SSD with Fast R-CNN network, the FPS will decrease to 8.9 FPS, but the model will archives 90.4% AP and 83.0% Recall.

On cholecystitis detection, by well-tuned MobileNet V2 neural network, the model achieves 92.78% AP, 92.22% Recall, and 93.33% Specificity on 9,500 ultrasound image

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at 7ms processed time per image on GPU (Nvidia GeForce GTX 1080 Ti 11GB).

Conclusions: Using machine learning modules to identify abdominal diseases by abdominal ultrasound image, the results of the training in the gallstones and cholecystitis were quite good. Through machine learning modules for various kinds of hepatobiliary diseases, it can help clinicians to diagnose the disease by abdominal ultrasound and even provide remote medical care. In the future, the computer-assisted system may allow non-physician operator to help initial diagnosis.

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在沒有明顯影像學證據的情況下，探討膽道 結石的預測因子。 PREDICTORS OF CHOLEDOCHOLITHIASIS IN PATIENTS WITHOUT CONVINCED IMAGE EVIDENCE: THE APPLICATION OF ASGE GUIDELINE IN TAIWAN. 2

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黃永輝 韓明倫 郭雨庭 陳介章 蘇浩俊 詹易達 2 1,2 廖偉智 王秀伯 1 臺大醫院內視鏡光學診斷暨治療中心 2 臺大醫院內科部

Background: For patients with suspected choledocholithiasis without convinced image evidence, EUS will be arranged to confirm the existence of CBD stone instead of performing ERCP directly due to the risks and cost of ERCP. Predictors for CBD stone were presented by western societies, but they may not suitable to our patients because of different clinical setting.

Aims: We aim to find out the potential predictors for choledocholithiasis in order to omit the necessity of EUS in uncertain cases.

Methods: From January, 2011 to August, 2019, patients who received EUS in NUTH for suspected CBD stone were included. Their information, laboratory and image studies were collected retrospectively from the electronic medical records. Whether ERCP would be performed after EUS depended on the judgement of clinicians. Patients who had received CBD manipulation before the index EUS (such as PTCD or ERCP) will be excluded.

Results: 139 patients received EUS for suspected CBD stone during the study period. After exclusion, 106 patients were included for analysis. CBD stone was detected by EUS in 51 patients. 45 of the 51 patients received ERCP, all of them had CBD stone during lithotripsy. Patients with advanced age, CBD dilatation in abdominal echo/CT and CBD stone in CT scan were the only predictors for CBD stone in EUS (Table 1 and 2). Laboratory data include total bilirubin and gammaglutamyl transferase were not capable to predict the presence of CBD stone. Of note, the difference in stone detection rate was not significant between patients in high and moderate likelihood group, of whom were classified according to the ASGE guideline. The diagnostic accuracy of abdominal echo and CT for CBD stone were 57% and 65% respectively.

Conclusions: Age and CBD dilatation in image study were the only two predictors for patients with choledocholithiasis without obvious image evidence. Laboratory test has no role in prediction. Therefore, the classification system presented by western societies was not validated in our patients.

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2020 消化系聯合學術演講年會

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評估數位膽管內視鏡於肝門膽管癌之可切 除性的角色 TO EVALUATE THE ROLE OF DIGITAL CHOLANGIOSCOPY USING SPYGLASS OVER THE RESECTABILITY OF PERIHILAR CHOLANGIOCARCINOMA 1

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陳冠至 林政寬 李宗熙 林建助 王秀伯 陳國鋅 1 鍾承軒 1 亞東紀念醫院 2 臺大醫院

Background: To precisely assess the disease extent and resectability of perihilar cholangiocarcinoma is still challenging. Bismuth-Corlette classification is so far the most widely used system for assessment of resectability of prehilar cholangiocarcima. Magnetic resonance image(MRI) combined with magnetic resonance cholangiopancreatography (MRCP) is regarded as an excellent tool for evaluation the extent of disease, however about 20 percent of cases is still understaged by MRCP. Aims: We tried to use digital cholangioscopy with Spyglass (Boston Scientific, Natick, Massachusetts, USA) to localize perihilar cholangiocarcinoma more precisely to guide further surgical strategy.

Methods: From June 2015 to December 2020, the patients who underwent digital cholangioscopy with Spyglass in Far Eastern Memorial Hospital for evaluating perihilar cholangiocarcinoma were retrospectively enrolled. The accuracy of evaluating extent of disease according to Bismuth-Corlette classification by cholangioscopy with Spyglass was compared with the image study before Spyglass by using surgical pathologic diagnosis as gold standard.

Results: There were 36 patients who underwent cholangioscopy with Spyglass in Far Eastern Memorial Hospital during study period. Among them, 4 patients with suspected perihilar cholangiocarcinoma who received cholangioscopy with Spyglass and had final surgical pathological diagnosis were enrolled. They were all male with a mean age of a 55.5 years (range, 35 to 79 years).

All of them underwent contrast enhanced computed tomography (CT), and one case also received MRI/ MRCP study before cholangioscopy with Spyglass. Using cholangioscopy with Spyglass for determining the extent of disease showed 100% accuracy by using surgical pathologic diagnosis as gold standard with two BismuthCorlette classification type 4, one type 3A, and one

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type 3B, while contrast enhanced CT showed only 25% accuracy. One case was changed from intentional extended left hepatectomy to extended right hepatectomy due to one skipped cancerous looking like lesion found in posterior branch of right intrahepatic duct, while the other three cases were remained in original surgical plan of extended left hepatectomy.

Conclusions: We demonstrated the excellent performance of cholangioscopy with Spyglass for evaluating tumor extent of perihilar cholangiocarcinoma, and it may change surgical plan according to the findings. Further study is warranted to demonstrate its application on localization of perihilar cholangiocarcinoma for providing precise treatment.

2020 消化系聯合學術演講年會

主題：其他消化道疾病

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51

台灣發炎性腸道性腸道疾病患者之糞便微 生物譜 FECAL MICROBIOTA PROFILE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN TAIWAN 1,3

1,2,3

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1,3

張天恩 羅景全 楊永正 黃怡翔 侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 衛生福利部基隆醫院 3 國立陽明大學醫學院 4 國立陽明大學生物醫學資訊研究所

1,3

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease that associated with complicated interaction between immune, gut microbiota and environmental factors in a genetically vulnerable host.

Dysbiosis is often seen in patients with IBD. Aims: To investigate the fecal microbiota in patients with IBD and compared to healthy controls in Taiwan.

Methods: In this cross-sectional study, we investigated fecal microbiota in 20 patients with IBD and 48 healthy controls. Fecal samples from both IBD patients and controls were analyzed by next-generation sequencing method.

Results: The IBD group showed lower bacterial richness and diversity (p = 0.03 and < 0.01, respectively) compared to the control group. The principal coordinate analysis also revealed significant structural difference between the IBD and the control group. In genus level, Faecalibacterium (p < 0.01), Parabacteroides (p = 0.03), Ruminococcaceae UCG-002 (p < 0.01) and Paraprevotella (p = 0.03) were significant lower in the IBD group compared to the controls. Bifidobacterium (p < 0.01), Ruminococcus gnavus group (p < 0.01), Streptococcus (p = 0.02) and Blautia (p = 0.01) were significant higher in the IBD group compared to the control group. The discriminant analysis revealed that Lactobacillus and Veillonella as dominant genera in the stool microbiome of the IBD group, whereas genera Faecalibacterium was dominant in the control group.

Conclusions: Compared to the healthy control, the IBD group showed dysbiosis with a significant decreased in both richness and diversity of gut microbiota.

上下消化道術後的腸道菌叢之變化 DIFFERENCES IN INTESTINAL MICROBIOTA PROFILING AFTER UPPER AND LOWER GASTROINTESTINAL SURGERY 1

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1,3,4

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丁柏翔 林毅軒 羅景全 張天恩 黃怡翔 侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學附設醫院內科部 3 衛生福利部基隆醫院 4 國立陽明大學內科學系

Background: The subsequent changes of metabolic profiles and microbiota status after upper and lower gastrointestinal surgery are not clear.

Aims: We aimed to investigate and compare long-term effects of metabolic profiles and microbiota status in early gastric cancer patients post curative total gastrectomy and early colorectal cancer (CRC) patients after curative colectomy to the controls.

Methods: In this cross-sectional study, we analyzed metabolic syndrome occurrence in 10 patients after curative total gastrectomy with Rou-en-Y esophago- jejunostomy (RYEJ) anastomosis and 11 patients after curative partial colectomy with right hemicolectomy (RH) and 33 age-sex matched controls. Fecal samples were also analyzed by next-generation sequencing method.

Results: . Metabolic syndrome occurrences were significantly lower in patients after subtotal gastrectomy with RYEJ than in controls over the long term (> 8 years) follow-up (P < 0.05). Compared with the control group, patients who received RH only had a trend of higher serum fasting glucose (P = 0.10) . . The diversity of gut microbiota significantly decreased after partial colectomy with RH (P < 0.05), but not total gastrectomy with RYEJ. . Compared with the control group, the principal component analysis revealed significant differences in bacterial genera abundance after RYEJ and RH (P < 0.001). . Prevotella and Pyramidobacter were the two most abundant genera after RYEJ, while Bacteroides and Fusobacterium were the top two genera of discriminant abundance in patients after RH (P < 0.05).

Conclusions: Early gastric cancer patients after total gastrectomy with RYEJ had a lower occurrence of metabolic syndrome than the controls during long term follow-up. In parallel with the metabolic improvements, gut microbial diversity also significantly decreased after partial colectomy with RH.

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雙氣囊小腸鏡診斷之小腸惡性腫瘤：中台灣 一醫學中心之十年經驗 MALIGNANT TUMORS OF THE SMALL BOWEL DIAGNOSED BY DOUBLEBALLOON ENTEROSCOPY: A TENYEAR EXPERIENCE OF A MEDICAL CENTER IN MID-TAIWAN 1

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吳宜樺 周仁偉 張家熙 鄭庚申 許貝池 陳宗偉 1 中國醫藥大學附設醫院肝膽腸胃內科 2 中國醫藥大學附設醫院病理科 3 亞洲大學附設醫院肝膽腸胃內科

Background: The malignant tumors of the small bowel are relatively rare, and their pre-operative diagnosis is usually difficult and delayed.

Aims: This study was aimed to investigate the clinical characteristics of patients with malignant small bowel tumors who underwent double-balloon enteroscopy.

Secondary end points were to evaluate the usefulness and safety of double-balloon enteroscopy for the diagnosis of patients with malignant small bowel tumors derived from other previous procedures.

Methods: From January 2008 to November 2019, we retrospectively analyzed consecutive patients who underwent double-balloon enteroscopy at a medical center in mid-Taiwan over a 10-year period. Patients were diagnosed as malignant small bowel tumors were enrolled into our study.

Results: Double-balloon enteroscopy (per oral 43, per anal 4, per oral and anus:8) were performed in 750 patients.

Small bowel tumors were diagnosed in 102 patients (102/750; 13.6%), of which 55 patients (55/102; 53.9%) (29 males, a mean age of 61.87 years) had malignant tumors: 27 had gastrointestinal stromal tumors (49.0%), 12 had adenocarcinoma (21.8%), 7 had metastatic cancer (12.7%), 6 had lymphoma (10.9%), 1 had angiosarcoma (1.8%), 1 had carcinoid (1.8%), and 1 had desmoid tumor (1.8%). The most common indications for double-balloon enteroscopy in patients with malignant small bowel tumors were obscure gastrointestinal bleeding (n=38; 69.0%).

The concordance rate of diagnoses based on doubleballoon enteroscopy with diagnoses based on small bowel barium study, computed tomography, and capsule endoscopy among patients with malignant small bowel tumors was 54.1% (13/24), 65.9% (29/44), and 76.9% (10/13), respectively. After the results of double-balloon enteroscopy, surgical treatment was performed in 67.2 %

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(37/55) of patients with malignant small bowel tumors and chemotherapy treatment was performed in 25.4% (14/55) of patients with malignant small bowel tumors.

Conclusions: In our present study, we found approximately 14.5% of patients who underwent double-balloon enteroscopy had small bowel tumors, 53.9% of small bowel tumors are malignant. The most common indication for double-balloon enteroscopy in patients with malignant small bowel tumors was obscure gastrointestinal bleeding.

Double-balloon enteroscopy is a very useful modality in diagnosing malignant small bowel tumors and has an important impact on therapeutic plans and short-term clinical results.

2020 消化系聯合學術演講年會

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metformin 重編程產婦高脂飲食誘導的產婦 腸道微生態失調的胎兒肝損傷 METFORMIN REPROGRAMMING OF MATERNAL HIGH-FAT DIET -INDUCED MATERNAL DYSBIOSIS-DRIVEN FETUS LIVER STRESS

使用高溫高壓蒸氣滅菌方式清洗降低腸胃 內視鏡可拆式配件之汙染的可行性 STEAM STERILIZATION DECREASES CONTAMINATION OF FLEXIBLE GASTROINTESTINAL ENDOSCOPY’S VALVES: A PRACTICAL METHOD TO DECREASE ENDOSCOPY-RELATED IATROGENIC INFECTION

刁茂盟 盧怡庭 黃瀛賢 唐國書 陳智仁 高雄長庚紀念醫院小兒科 Background: The deleterious effects of high-fat diet can impact fetal rat liver and this can cause later development of NAFLD. Aims: Our aim is to study the fetus liver caused- by maternal high-fat diet-induced maternal dysbiosis.

Methods: After confirmation of pregnancy on the 14th day after mating, pregnant females Sprague-Dawley rats are randomly divided for the prenatal high--fat diet exposure paradigm (HFD) or left undisturbed (NC) until delivery.

The other HFD was fed with metformin (HMf). The fetus was sacrificed at gestation 21 days.

Results: The Western blot of caspase3 (apoptosis), TNFalpha (inflammation) in male fetus liver was decreased in HMf compared to HFD (P<0.05). Phosphor-AKT (survival), GPX1 (antioxidative stress) was higher in HMf than HFD group (P<0.05). The relative microbiota abundance was different among the 3 groups. Maternal stool in HFD during pregnancy was demonstrated to increase Verrucomicrobiales in Order (related to fatty liver), and this is decreased after metformin given.

Conclusions: Oxidative stress with inflammation and the regulation of gut microbiota plays a vital role in the fetus to adult liver steatosis, and prenatal metformin may reprogram this.

賴佳業 陳維娜 戴君惜 楊勝舜 張繼森 柯忠旺 臺中榮民總醫院 Background: Endoscopy-associated pathogen transmission has been recognized as an important issue of safety.

Inadequate decontamination procedures and equipment malfunction are two leading causes of post-endoscopic infection and contamination. The current guideline suggests manual cleaning, followed by high-level disinfection(HLD) as standard reprocessing procedure. The FDA has highlighted the cross-contamination risk associated with valves(suction, air/water and biopsy valve) when used with flexible gastrointestinal endoscope accessory in 2018. Single-use valves are still in development, and the feasibility remains unclear due to cost-effectiveness.

Aims: We aimed to evaluate the effectiveness of manual cleaning, and the feasibility of HLD followed by steam sterilization(SS) as a practical method in real-world for valve reprocessing to decrease contamination rate.

Methods: All valves from the endoscopy were reprocessed by 3 steps. Manual cleaning was followed by HLD, and HLD was followed by SS. We performed manual cleaning in 2 situations, under and without supervision. We cultured the samples of valves from the endoscopy after each reprocessing step. The SS protocol was under 134°C-136°C and 31-32 pounds per square inch for 4 minutes. The samples for cultures were acquired from 1ml bottom layer fluid by using 40 ml sterile distilled water soaking valves, followed by vibration with a vibrating tester for 1 minutes and centrifugation under 3000rmp for 5 minutes. All samples were cultured under 35°C for 48 hours.

Results: 22 sets of cultures were obtained(8 sets under real-time supervision and 14 sets without supervision when manual cleaning). The positive culture rate was 77% after manual cleaning(63% under supervision and 86% without supervision), 32% after HLD(including 9% of false negative cultures which became positive after SS, 13% under supervision and 43% without supervision) and 18% after SS(0% under supervision and 29% without

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2020 消化系聯合學術演講年會

55 supervision). The positive high-concern organisms culture rate was 59% after manual cleaning(25% under supervision and 79% without supervision), 14% after HLD(including 5% of false negative cultures which became positive after SS, 13% under supervision and 14% without supervision) and 5% after SS(0% under supervision and 7% without supervision). The major high-concern organisms were Pseudomonas, Klebsiella and Enterococcus species. The cost of SS was around 0.1 USD for 1 valve in Taiwan.

Conclusions: Adequate and well-qualified manual cleaning plays a central role in decontamination procedures.

However, it seems not reliable in terms of the consistency in real-word practice. HLD followed by SS is superior to HLD alone, and it could reduce 33% contamination rate in this situation. If adequate manual cleaning can be ensured, it is possible to erase all the contamination by HLD followed by SS.

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全新內臟疼痛安慰劑效應動物模型的行為 及分子變化 BEHAVIORAL AND MOLECULAR CHANGES IN A NOVEL RAT MODEL OF VISCERAL PLACEBO ANALGESIA 1

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林弘恩 劉佩怡 王彥博 蔡佳芬 侯明志 1,3 1,2,3,5 李發耀 盧俊良 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學腦科學研究所 3 國立陽明大學醫學院 4 臺北榮民總醫院精神醫學部 5 臺北榮民總醫院內科部內視鏡診斷暨治療中心

Background: High placebo response is commonly observed in treating visceral pain of the patients with irritable bowel syndrome. The molecular mechanisms underlying the visceral placebo process remain unclear.

Aims: By using morphine conditioning, we aimed to establish a rodent model of visceral placebo analgesia and explore its molecular mechanisms.

Methods: Threshold of visceral pain was determined by colorectal distension (CRD) and simultaneous electromyography recording for 11 days in rats.

Conditioning with intraperitoneal morphine injection with blue light cue was administered at Days 3/4 and Days 7/8.

Cue without morphine was given at Day 10 to determine the extent of placebo effect. Naloxone before CRD was applied at Day 10 in the morphine-conditioned rats.

Microinjection of dermorphin-saporin (Derm-SAP) for ablation of the morphine-expressing neuron into anterior cingulate cortex (ACC) was given at 28 days before the experiment. Expression of μ-opioid receptor and second messengers (ERK 1/2, JNK and p38) along mitogenactivated protein kinase pathways in ACC were measured.

Results: Visceral pain threshold was significantly increased after morphine conditioning (n =14; day1 vs. day10: 25.48 ± 1.73 mmHg vs. 33.57 ± 1.46 mmHg, P < 0.001), suggestive of successful induction of visceral placebo analgesia. Naloxone would abolish the visceral placebo analgesia, indicative of involvement of opioid pathway.

Ablation of morphine receptor-expressing neurons in ACC blocked visceral placebo analgesia (P=0.481). Increased expression of phosphorylation of ERK 1/2, but not JNK and p38, in the ACC neurons were associated with the visceral placebo analgesia.

Conclusions: A new rodent model of visceral placebo analgesia was successfully established. Endogenous opioid receptor with phosphorylation of ERK pathway in ACC plays an important role in mediating the placebo process.

This model encourages novel approach of the molecular mechanisms underlying visceral placebo analgesia.

2020 消化系聯合學術演講年會

主題：C 型肝炎（二） 56

慢性 C 型肝炎患者接受直接口服抗病毒藥 物治療後發生或復發肝癌之預測因子 PREDICTIVE FACTORS FOR INCIDENT OR RECURRENT HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C AFTER DIRECT-ACTING ANTIVIRAL THERAPY 1

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張凱智 許偉帆 賴學洲 莊伯恒 彭成元 林俊哲 1,4 1,4 黃冠棠 林肇堂 1 中國醫藥大學附設醫院內科部消化系 2 中國醫藥大學生物醫學研究所 3 中國醫藥大學中醫系 4 中國醫藥大學醫學系

Background: Hepatocellular carcinoma (HCC) is a major health problem in the world. Chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are well known etiologies for HCC. Nucleos(t)ide analogue therapy for CHB can reduce the incidence of HCC and improve survival in CHB patients and the predictive factors of HCC occurrence have been identified. Direct-acting antiviral agents (DAAs) have been the standard of care for CHC, but factors predictive of incident or recurrent HCC in CHC patients after DAA therapy are still unknown.

Aims: To evaluate factors predictive of incident or recurrent HCC in CHC patients after DAA therapy.

Methods: From 2012 Sep to 2019 Oct, 925 CHC patients who had received a complete course of DAA therapy were enrolled in this retrospective study. Demographic data, virological features, and factors associated with HCC occurrence recorded at baseline were collected.

Results: Of 925 patients, 401 (43.4%) patients were male, and 324 (35%), 218 (23.6%) and 309 (33.4%) patients had liver cirrhosis, diabetes mellitus and hypertension, respectively. The median age was 62 (52–69) years (first quartile–third quartile). The ALT, total bilirubin, albumin, AFP, and FIB-4 were 59 (37–101) U/L, 0.9 (0.6–1.2) mg/ dL, 4.3 (3.9–4.5) g/dL, 5.11 (2.89–11.55) ng/mL, and 3.08 (1.74–5.81), respectively. 628, 241, 9, 1, and 40 patients had genotype 1, 2, 3, 4, and 6 HCV infections, respectively, and 5 patients had mixed genotype HCV infection (one patient lacked HCV genotype data). 906 of 925 patients (97.9%) achieved sustained virologic response at 12 weeks after DAA therapy. 734 (79.4%), 81 (8.8%), 44 (4.8%), 21 (2.3%), and 44 (4.8%) patients had no HCC, HCC before or during DAA therapy, active HCC, incident HCC after DAA therapy, and recurrent HCC, respectively. The time

to recurrence was 25.1 (12.6–36.5) months among 44 patients with recurrent HCC. One patient was diagnosed with HCC (T1N0M0) and underwent curative surgery during DAA therapy. Of 109 patients with HCC after DAA therapy, 45, 44, 13, and 7 patients belonged to TNM stage I, II, III, and IV, respectively, and 59, 30, 19, and 1 patients belonged to Barcelona Clinic Liver Cancer stage A, B, C, and D, respectively. After excluding patients with active HCC before, during, and after DAA therapy (n = 44), univariate Cox regression analysis identified age (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.036–1.088, p < 0.001), platelet count (HR 0.984, 95% CI 0.978–0.989, p < 0.001), AST (HR 1.005, 95% CI 1.000–1.009, p = 0.034), total bilirubin (HR 1.435, 95% CI 1.081–1.905, p = 0.012), FIB-4 (HR 1.093, 95% CI 1.045–1.142, p < 0.001), hypertension (HR 2.401, 95% CI 1.449–3.980, p = 0.001), liver cirrhosis (HR 7.030, 95% CI 3.967–12.455, p < 0.001), Child score ≥6 (HR 2.511, 95% CI 1.300–4.851, p = 0.006), model for end-stage liver disease score > 8 (HR 2.555, 95% CI 1.460–4.470, p = 0.001), and HCC before DAA therapy (HR 16.941, 95% CI 9.717–29.537, p < 0.001) as the significantly associated factors. Liver cirrhosis (HR 2.200, 95% CI 1.082–4.473, p = 0.029) and HCC before DAA therapy (HR 12.677, 95% CI 6.395– 25.129, p < 0.001) were independent predictors of incident or recurrent HCC in multivariate Cox regression analysis.

Conclusions: HCC surveillance should be implemented in CHC patients after DAA therapy, especially among those with liver cirrhosis or HCC before DAA therapy.

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C 型肝炎基因型會影響接受口服抗病毒藥物 肝癌患者預後 HEPATITIS C VIRUS GENOTYPE AFFECTS PROGNOSIS IN CHC-HCC PATIENTS AFTER DIRECT ACTING ANTIVIRAL THERAPY

C 型肝炎口服抗病毒 DAA 治療後之聲波輻 射脈衝影像 (ARFI) 與肝癌發生之關係 LIVER ACOUSTIC RADIATION FORCE IMPULSE IMAGING EVALUATION FOR HCV PATIENTS POST DIRECT ANTIVIRAL AGENTS AND HEPATOCELLULAR CARCINOMA OCCURRENCE

滕威 鄭文睿 陳威廷 林俊彥 沈一嫻 林口長庚紀念醫院胃腸肝膽科 Background: The influence of HCV genotype in patients with hepatocellular carcinoma (HCC) after curative treatment is still undetermined.

Aims: This study aimed to investigate whether the HCV genotype affected the tumor recurrence in CHC-HCC patients receiving direct acting antiviral therapy (DAA).

Methods: From 2015 to 2017, 79 CHC-HCC patients received DAA therapy after curative HCC treatment in Chang Gung Memorial Hospital, Linkou medical center were retrospectively recruited. The pre-treatment host factors, tumor status, liver biochemistry and noninvasive fibrosis markers were collected. Cox regression model was used to identify independent predictors of tumor recurrence.

Results: Among 79 treatment-naive CHC-HCC patients, the mean age were 67.1 ± 8.5 year-old and most patient was genotype 1 (86.1%). During a median follow-up of 29.3 months from HCV treatment, seven patients encountered HCC recurrence during antiviral treatment, while the other 39 patients had HCC recurrence after end of antiviral therapy (EOT). There was no significant difference of baseline characteristics including age, gender, tumor burden and tumor treatment modalities between genotype 1 and 2 except that patients with genotype 2 higher ALBI grade II/III (54.5% vs. 36.8%, p= 0.0008). By Cox regression multivariate analysis, pre-HCV treatment ALBI grade II/ III (aHR: 2.374, p=0.0041) and genotype 2 (aHR: 2.828, p= 0.0064) were independent predictor for HCC recurrence after DAA therapy. Patients with genotype 2 had shorter recurrence free interval (RFI) than genotype 1 (median RFI: 6.2 (95%CI: 2.3-10.0) vs. 17.7 (95%CI: 7.2-28.3), P=0.0318; 1- and 2- year cumulative HCC recurrence rate: 80%, 90% vs. 43%, 53% respectively, Log rank test, P=0.008).

Conclusions: HCV genotype does influence post DAA treatment HCC recurrence rate in CHC-HCC patients receiving curative HCC treatment.

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梁博程 林宜竑 黃釧峰 黃駿逸 葉明倫 戴嘉言 楊正福 黃志富 莊萬龍 余明隆 高雄醫學大學附設醫院 Background: Liver acoustic radiation force impulse imaging (ARFI) is a reliable non-invasive measurement for liver stiffness in patients with hepatitis C virus (HCV) infection. HCV treatment with direct antiviral agents (DAA) would change ARFI level and there have been less data to discuss between post-DAA ARFI and the occurrence rate of hepatocellular carcinoma (HCC).

Aims: To study the association of liver ARFI, especially post-DAA values, and new onset of HCC after HCV eradication.

Methods: A total of 118 HCV patients with DAA therapy during 2014-2019 in Kaohsiung medical university hospital were enrolled for analysis. All of them received the baseline and at least one-time ARFI test after DAA. Those cases with viable HCC or just post HCC therapy within 6 months before DAA were excluded.

Results: The study group included 60.2% males with mean age of 59.6 years. 100% achieved sustained virological response. Forty patients experience three times ARFI measurements. The mean values were 1.97m/s (baseline), 1.52m/s (post-DAA month 3), and 1.43m/s (post-DAA > year 1), and p values were < 0.001 (baseline vs month 3, or baseline vs > year 1) and 0.077 (month 3 vs > year 1). All of the 118 patients had a median follow-up of 29.5 months and 6 developed HCC. Compared to baseline values, those with higher post-DAA ARFI values (cutoff: 2.5m/s) were at risk for HCC occurrence (HR= 6.64, 95%CI= 1.2-36.8, p= 0.03).

Conclusions: Higher ARFI values after DAA seemed to have a higher risk of HCC development.

2020 消化系聯合學術演講年會

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血清 Mac-2- 結合蛋白醣基化異構物可預測 未治療之慢性 C 型肝炎病患之長期併發症 SERUM MAC-2-BINDING PROTEIN GLYCOSYLATION ISOMER LEVEL HELP TO PREDICT THE LONGTERM COMPLICATIONS IN UNTREATED CHRONIC HEPATITIS C PATIENTS 1

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張善涵 蘇東弘 李美璇 劉俊人 陳培哲 1,2 1,2 4 1,2 6 1 楊宏志 劉振驊 陳祈玲 曾岱宗 陳健弘 李宣書 1,2,7 7 1,2,4,5 陳定信 陳建仁 高嘉宏 1 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科 2 國立臺灣大學醫學院附設醫院肝炎研究中心 3 國立陽明大學臨床醫學研究所 4 國立臺灣大學醫學院臨床醫學研究所 5 國立臺灣大學醫學院附設醫院醫學研究部 6 國立臺灣大學醫學院附設醫院雲林分院內科部 7 國立中央研究院基因體研究中心

2.713), intermediate (HR: 1.477, 95% CI: 1.278-1.706), and high (HR: 1.102, 95% CI: 1.039-1.169) baseline Fib4 levels. In patients with intermediate Fib-4 level, M2BPGi helps to predict subsequent HCC (HR: 1.502, 95% CI: 1.272-1.774).

Conclusions: Serum M2BPGi level helps to predict subsequent cirrhosis regardless of baseline Fib-4 level. In patients with intermediate fib-4, M2BPGi can predict the subsequent development of HCC. M2BPGi can supplement Fib-4 level in the management of chronic hepatitis C.

Background: The fibrosis-4 index (Fib-4) and serum Mac2-binding protein glycosylation isomer (M2BPGi) have been introduced to correlate with liver fibrosis in patients with chronic hepatitis C. Aims: To investigate the predictive role of serum M2BPGi for the development of cirrhosis, hepatocellular carcinoma and death and the clinical scenario for M2BPGi measurement.

Methods: We conducted a retrospective study to include untreated chronic hepatitis C patients who received longitudinal follow-up at the liver clinic of National Taiwan University Hospital during 1986-2014. Patients were screened if they had positive anti-HCV, HCV RNA or had a diagnosis of chronic hepatitis C. We excluded patients with incomplete medical records, coinfection of HBV or HIV, HCC development in the first year, or a follow-up duration less than 3 years.

Results: A total of 1155 patients were included in the ERADICATE-C cohort. After excluded patients without stored serum for M2BPGi measurement, 772 patients were included. Their mean age was 55 years, 63% were female and 74 patients had baseline cirrhosis. The median M2BPGi level was 1.2 COI and Fib4 level was 2.1. After 12 years of follow-up, 207, 163 and 93 patients newly developed cirrhosis, HCC and death, respectively. We investigate the predictive role of M2BPGi in patients with low (<1.45), intermediate (1.45-3.25), and high (>3.25) Fib-4 levels, respectively. M2BPGi level helps to predict subsequent cirrhosis in patients with low (HR: 1.764, 95% CI: 1.147-

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主題：肝腫瘤（二） 60

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口服抗病毒藥物清除Ｃ肝病毒後脂質表現 於基因型第一型與第二型之差異 HCV G1 AND G2 PATIENT EXERTED DISTINCT LIPID PROFILES FOLLOWING VIRAL CLEARANCE BY DIRECT ACTING ANTIVIRALS

在一個亞洲族群無肝硬化的肝細胞癌患者 之臨床特徵及慢性肝病病因分析 CHARACTERISTICS AND AETIOLOGIES OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITHOUT CIRRHOSIS IN AN ASIAN COHORT

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鄭斌男 孫宏羽 邱宏智 邱彥程 楊孔嘉 1 成功大學醫學院附設醫院內科部 2 成功大學醫學院檢驗生物技術學系

Background: Genotype of hepatitis C virus (HCV) has different impacts and features on lipid profiles. The association of clearance of HCV by direct acting antivirals (DAA) and changes of lipid profiles in genotype (GT) 1 and GT 2 needs to study.

Aims: To address the long-term effect of DAA on lipid profiles between GT1 and GT2 chronic hepatitis C (CHC) patients Methods: In total of 36 CHC patients including 20 patients infected with GT1 and 16 patients infected with GT2 were enrolled. Lipid profiles and loading capacity of VLDL/LDL were analyzed before DAA treatment, SVR12, 6 months and 12 months following SVR12.

Results: All of the 36 patients achieved SVR12. The level of triglyceride (TG) and total cholesterol (Chol) was comparable between two study groups. The plasma TG levels fluctuated slightly in HCV G1 patients, but showed an increasing pattern in HCV G2 patients during the period of treatment. In both genotypes, Chol level significantly increased from the baseline to SVR12 and month 6 following SVR12. Interestingly, HCV G2 patients exerted higher HDL at baseline, but was gradually decreased at month 6 (∆-10%) and month 12 following SVR12 (∆-10%).

In contrast to HCV G2 patients, HDL level was gradually increased in HCV G1 patients during the period of followup (month 6 (∆20%) and month 12 following SVR12 (∆15%).

The Chol/HDL ratio and the dynamic changes of Chol/ HDL ratio in HCV G2 patients were gradually increased from before DAA treatment to month 12 following SVR12 (p =0.015). The change of Chol/HDL ratio in HCV G2 patients was increased in the period of month 6 and month 12 following SVR12 (month 6 (∆37%) and month 12 following SVR12 (∆38%) compared to that of HCV G1 patients (month 6 (∆0%) and month 12 following SVR12 (∆-10%).

Conclusions: The results suggested that DAA had distinct effect on lipid metabolism of HCV G1 and G2 patients.

HCV G2 patient might exert higher risk of cardiovascular disease than GT1 after receiving DAA treatment.

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黃子昕 胡琮輝 鄭汝汾 林志哲 王景弘 顏毅豪 1 高雄長庚紀念醫院胃腸肝膽科 2 高雄長庚紀念醫院放射診斷科 3 高雄長庚紀念醫院一般外科

Background: a recent study from United States reported that nearly 12% of hepatocellular carcinomas (HCCs) occurred in patients without underlying cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) was the most common liver disease in these patients.

Aims: To evaluate characteristics, aetiologies and outcomes of non‐cirrhotic HCC from an Asia medical center.

Methods: 2055 consecutive de-novo HCC patients and managed at Kaohsiung Chang Gung Memorial Hospital were enrolled from January 2011 to December 2017. The presence of underlying cirrhosis was assessed based on histology; if histology is not available, it was assessed based on image study.

Results: Of 2055 eligible patients with HCC, the presence of cirrhosis was assessed by histology (i.e. Ishak fibrosis stage 5 or 6) in 670 cases (32.6%); 529 (25.7%) had no underlying cirrhosis. Non-cirrhotic patients were younger (60.9 vs 62.5 years), more frequently males (78.1% vs71.3%). Among non‐cirrhotic patients, hepatitis B virus (HBV) was the most common liver disease (49.0%), followed by hepatitis C virus (HCV) (30.6%) and nonHBV, non-HCV, non-alcohol abuse (17.8%). Patients with non‐cirrhotic HCC had larger tumors (5.9 vs 4.7 cm), more frequently underwent liver resection (66.0% vs 17.4%) (P < .001) and had better overall survival than cirrhotic HCC patients (median 5.67 vs 2.83 years, P <0.001).

Conclusions: Nearly 26% of HCCs occurred in patients without underlying cirrhosis.

HBV was the most common liver disease in these patients.

The survival was better in non‐cirrhotic patients compared with cirrhotic patients.

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蕾莎瓦和癌瑞格連續療法治療晚期肝細胞 癌：高雄長庚紀念醫院的現實經驗 SEQUENTIAL THERAPY WITH SORAFENIB AND REGORAFENIB FOR ADVANCED HEPATOCELLULAR CARCINOMA: REAL-WORLD EXPERIENCE IN KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL

BCLC-B 並有多顆腫瘤的肝癌病人接受經動 脈化學栓塞後之治療反應及存活預測分析 PREDICTORS OF RESPONSE AND SURVIVAL AFTER TRANSARTERIAL CHEMOEMBOLIZATION FOR PATIENTS WITH BCLC-B HEPATOCELLULAR CARCINOMA WITH MULTIPLE TUMORS

1

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郭垣宏 盧勝男 紀廣明 洪肇宏 陳建宏 王景弘 1 高雄長庚紀念醫院胃腸肝膽科系 2 嘉義長庚紀念醫院胃腸肝膽科

Background: Conversion from sorafenib to regorafenib has been as evidence-based treatment strategy in patients with unresectable advanced hepatocellular carcinoma (HCC).

Aims: This study aimed to assess the efficacy of sequential therapy with sorafenib and regorafenib in clinical practice.

Methods: From Apr 2013 to Dec 2019, 54 consecutive patients with Barcelona clinical liver cancer (BCLC) HCC stage C and Child A received sequential therapy with sorafenib and regorafenib in our hospital, and their medical records were collected for further analysis. Radiological responses was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 Results: were 43(79.6%) male patients and 11(20.4%) females patients, with a mean age of 62.6 years old. The distribution of etiology of HCC was hepatitis B virus infection in 25(46.3%) patients, hepatitis C virus infection in 21(38.9), B+C in 1(1.9%) and non-B, non-C in 7(13%), respectively. The median treatment duration of sorafenib and regorafenib was 6.7 months (range: 1.1-43.1 months) and 3.9months (range: 0.2-30.3 months), respectively. After excluding 11 patients remained regorafenib treatment, 17 (39.5%) of 43 patients could still afford following sequential systemic therapies after regorafenib failure.

There were 15(27.8%) patients died during the followup. The median overall survival of sorafenib-regorafenib was 17.9 months (range: 2.9-84 months). In multivariate analysis, albumin-bilirubin (ALBI) grade II and higher alpha-fetoprotein (AFP) level at the time of regorafenib start were associated with mortality in patients with sorafenib-regorafenib sequential therapy.

Conclusions: In real-world clinical practice, regorafenib was still effective in patients with advanced HCC who progressed on first-line sorafenib, especially in those patient with ALBI grade I liver function and lower AFP level at the beginning of regorafenib use.

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1,2,4

張可斌 李懿宬 齊振達 李潤川 侯明志 黃怡翔 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院放射科 4 國立陽明大學臨醫所

B a c k g ro u n d : F o r p a t i e n t s w i t h B C L C s t a g e B hepatocellular carcinoma (HCC) with multiple tumors, transarterial chemoembolization (TACE) is an effective treatment. However, the predictors of response and survival after TACE remain unclear.

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

Methods: Consecutive 407 treatment-naïve patients with BCLC-B HCC with multiple tumors undergoing TACE as the initial treatment were retrospective enrolled. Radiologic response after first TACE was evaluated by modified RECIST criteria. Factors associated with response and overall survival (OS) were analyzed.

Results: Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 10.9%, 28.8%, 25.4% and 35% of patients, respectively, after first TACE. AFP ≤200 ng/ml (odds ratio (OR)=2.616, p=0.039) and tumor size ≤5 cm (OR=2.164, p=0.462) were the independent predictors of CR. Out of up-to-11 criteria was the only independent predictor of PD (OR=1.878, p=0.007). The median OS in patients with CR, PR, SD and PD were 37.5, 40.4, 22.3 and 14.1 months, respectively. By multivariate analysis, AFP >200 ng/ml (hazard ratio (HR)=2.061, p<0.001), ALBI grade 2 or 3 (HR=1.318, p=0.033), out of up-to-11 criteria (HR=2.338, p<0.001) were independent predictors of OS. The ALBITAE model could classify patients into very low, low, intermediate and high risk of mortality (median OS of 50.1, 31.0, 17.4 and 4.4 months, respectively, p<0.001).

Conclusions: AFP and tumor size are predictors of CR while up-to-11 criteria is the predictor of PD after first TACE for BCLC-B HCC patients with multiple tumors.

The ALBI-TAE model consisted with ALBI grade, AFP and up-to-11 criteria can be applied to discriminate patient’s survival after TACE.

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肝動脈化療合併標靶治療與肝動脈化療於 BCLC C 病人的比較 HEPATIC ARTERIAL INFUSION CHEMOTHERAPY PLUS SORAFENIB VERSUS HEPATIC ARTERIAL INFUSION CHEMOTHERAPY ALONE IN PATIENTS WITH BCLC STAGE C HEPATOCELLULAR CARCINOMA 莊逸群 孫煒智 蔡維倫 鄭錦翔 高雄榮民總醫院 Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC), but the survival benefit and treatment response are unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) was considered the treatment of choice in patients with portal vein invasion before the introduction of sorafenib. Whether adding sorafenib to HAIC improved survival than HAIC alone is controversial.

Aims: This retrospective study aims to compare HAIC plus sorafenib with HAIC alone in patients with BCLC stage C HCC. Methods: From 2005 to 2017, patients with BCLC stage C HCC receiving HAIC alone or combination therapy with sorafenib and HAIC were reviewed. Baseline data, treatment response and overall survival were determined and compared between the two groups.

Results: A total of 187 patients were enrolled, including 138 patients received HAIC and 51 patients received HAIC plus sorafenib. Patients in the HAIC/sorafenib group were younger (55.3y/o versus 59.9y/o, p=0.02) and had larger tumor size (11.9cm versus 10.1cm, p=0.03). The overall response rate was 25% (CR: 8.8% PR: 16.2%) in HAIC group and 35.3% (CR: 5.9% PR: 29.4%) in HAIC/ sorafenib group (p=0.10). The disease control rate was 42.6% in HAIC group and 56.9% in HAIC/sorafenib group (p=0.08). Both groups had similar overall median survival of 8 months. The 3-month, 6-month, and 12-month survival rate were 82.4%, 55.9%, 36% in HAIC group and 84.3%, 64.7%, 29.4% in HAIC/sorafenib group (p=0.47). For 48 patients with lymph node or distant metastasis, the overall response rate was 17.9% (CR: 7.1% PR: 10.8%) in HAIC group and 40.0% (CR: 5% PR: 35%) in HAIC/sorafenib group (p=0.08). The disease control rate was 50% in HAIC group and 55% in HAIC/sorafenib group (p=0.73). The overall median survival was 7 months in HAIC group and 8.5 months in HAIC/sorafenib group (p=0.21). The

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3-month, 6-month, and 12-month survival rate were 75%, 57.1%, 21.4% in HAIC group and 85%, 70%, 25% in HAIC/sorafenib group (p=0.75).

Conclusions: Adding sorafenib to HAIC might increase treatment response than HAIC alone especially in patients with lymph node or distant metastasis, but did not improve overall survival. Adding sorafenib to HAIC seemed to have a better treatment response than sorafenib alone in phase III studies.

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IncRNA MALAT1 的多樣遺傳變異影響肝 細胞癌患者的風險和臨床病理特徵 GENETIC VARIANTS OF LNCRNA MALAT1 EXERT DIVERSE IMPACTS ON THE RISK AND CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA 1

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6

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阮蘭婷 張哲華 李祥麟 楊奕婕 蘇仕奇 林建良 9,10 3,6,11 楊順發 簡銘賢 1 阮綜合醫療社團法人阮綜合醫院內科部肝膽腸胃科 2 臺北醫學大學內科部 臺北市立萬芳醫院- 委託財團法人臺北醫學大學胸腔研 3 究中心 4 中山醫學院 5 中山醫學院外科部 6 臺北醫學大學臨床醫學研究所 7 長庚醫院人類全基因疾病研究核心實驗室 8 輔英科技大學附設醫院藥劑科 9 中山醫學院 10 中山醫學院醫學研究部 11 臺北醫學大學癌症轉譯醫學研究中心 Background: The long noncoding (lnc)RNA, metastasisassociated lung adenocarcinoma transcript 1 (MALAT1), plays a crucial role in the development of hepatocellular carcinoma (HCC). However, potential genetic variants (single nucleotide polymorphisms, SNPs) in MALAT1 that affect the susceptibility and progression of HCC have rarely been explored.

Aims: The aim of this study was to perform a case-control study in a Taiwanese population to identify the roles of MALAT1 SNPs in the risks and clinical characteristics of HCC. Methods: Three tagging SNPs, viz., rs3200401 C > T, rs619586 A > G, and rs1194338 C > A, in MALAT1 were genotyped by a TaqMan allelic discrimination assay in 394 HCC patients and 1199 healthy controls. The GenomeTissue Expression (GTEx) database was used to identify the regulatory potential of candidate functional MALAT1 variants. Transcriptomic data from samples of a normal liver, cirrhotic liver, dysplastic liver, and HCC were analyzed using the microarray datasets. RNA sequencing analysis, the visualization platform Gene Expression Profiling Interactive Analysis (GEPIA), and the Kaplan– Meier (KM) plot were used to determine whether MALAT1 expression was correlated with the prognosis of HCC

patients.

Results: A stratified analysis showed that younger patients (<55 years) with the MALAT1 rs619586 G allele had a decreased risk of HCC under a codominant model (AOR = 0.289, 95% CI: 0.108–0.773, p = 0.013) and dominant model (AOR = 0.286, 95% CI: 0.107–0.765, p = 0.013).

Female patients and patients with a smoking habit who carried the CA + AA genotype of rs1194338 had a lower risk of developing vascular invasion (p = 0.049) and a high Child–Pugh grade (B or C) (p = 0.036), respectively.

Under the dominant model, smokers with the MALAT1 rs3200401 CT + TT genotype had a higher frequency of hepatitis B virus (HBV) infection (p = 0.034). Moreover, the aspartate aminotransferase was higher in patients with the rs3200401 CT + TT genotype. Furthermore, analyses of clinical datasets revealed that MALAT1 expression level was gradually unregulated during HCC development from normal liver, cirrhotic liver, dysplastic liver to HCC and correlated with poor survival rates in HCC patients, especially in the hepatitis virus-infected population.

Conclusions: In this study, we identified the diverse allelic effects of MALAT1 genetic variants (rs3200401, rs619586, and rs1194338) which contribute to the susceptibility and clinicopathologic development of HCC in a Taiwanese population. These results can lead to a better understanding of risk and early detection of HCC.

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主題：上消化道疾病（二） 66

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內視鏡靜脈曲張結紮術後潰瘍出血的危險 因子 RISK FACTORS OF POST-BANDING ULCER BLEEDING FOLLOWING ENDOSCOPIC VARICES LIGATION AMONG CIRRHOTIC PATIENTS

以「持續方式」或「按需求方式」給與質子 幫浦抑制劑來治療巴瑞特氏食道症之長期 療效與安全性的比較 — 一多中心隨機控制 試驗 LONG-TERM EFFICACY AND SAFETY OF CONTINUOUS VS ON-DEMAND PROTON PUMP INHIBITOR THERAPY IN THE TREATMENT OF BARRETT’S ESOPHAGUS –A MULTICENTRE, RANDOMIZED CONTROLLED TRIAL

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陳俊瑋 林蔚然 林淳榮 蘇銘堯 邱正堂 1 林口長庚紀念醫院胃腸肝膽科 2 長庚大學醫學院

Background: Esophageal varices bleeding is a major complication of liver cirrhosis. Endoscopic varices ligation (EVL) has been recommend for prevention of esophageal varices bleeding as well as emergent treatment for acute esophageal varices bleeding. However, post-banding ulcer may lead to another lethal bleeding episode.

Aims: The aim of this study is to evaluate the risk factors of post-banding ulcer bleeding (PBUB) following endoscopic varices ligation.

Methods: From Jan 2015 to Oct 2017, patients underwent EVL were retrospectively evaluated in a tertiary medical center of northern Taiwan. The PBUB was defined as upper gastrointestinal bleeding episode with upper endoscopy evaluation within 2 weeks after EVL. The demographic, clinical and endoscopic data were collected at the time of EVL. Categorical variables were compared by using Chisquare test and continuous variables were compared by using the Student t test. Univariate and multivariate logistic regression was performed to determine the predictive factors of PBUB. Results: A total of 714 patients were included in this study. 41 (5.7%) patients suffered from PBUB. The baseline clinical and endoscopic characteristics of the studied patients were shown in Table 1. The mean age in post-banding ulcer bleeding group was significantly younger than that in non-PBUB group (53.95±11.53 Vs 58.35±12.48, p=0.028). In laboratory data, the prothrombin time, total bilirubin, ALT were significantly higher in PBUB group than those in non-PBUB group and albumin was significantly lower in PBUB group than that in non-PBUB group. The logistic regression for risk factors of PBUB was shown in Table 2. In univariate analysis, the prothrombin time (INR) >2.3, total bilirubin >3.0 mg/dl and sodium >150 mEq/l were associated with PBUB. In multivariate analysis, total bilirubin > 3.0 mg/dl and concomitant gastric varices were associated with development of PBUB. Conclusions: Cirrhotic patients with concomitant gastric varices and total bilirubin > 3.0 mg/dl have higher risks for development of PBUB.

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許秉毅 高崧碩 蔡成枝 鄭錦翔 施長碧 吳登強 1 中國醫藥大學安南醫院消化內科 2 高雄榮民總醫院內科部胃腸肝膽科 3 高雄長庚醫院內科部胃腸肝膽科 4 高雄醫學大學內科部胃腸肝膽科 5 臺灣胃酸相關疾病暨微菌叢聯盟 1,5

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Background: Barrett’s esophagus is the biggest risk factor of esophageal adenocarcinoma. Proton pump inhibitor (PPI) is recommended for symptom control and preventing progression of esophageal metaplastic epithelium in the management Barrett’s esophagus. However, concerns are growing about the serious adverse events linked to longterm use of PPI. Aims: (1) to compare the efficacies of on-demand and continuous PPI therapy for preventing progression of esophageal metaplastic epithelium in the treatment of Barrett’s esophagus, and (2) to investigate the impacts of the two treatment methods on gastric mucosal atrophy and bone mineral density.

Methods: Consecutive adult patients who had Barrett’s esophagus proven by esophageal biopsy were randomly to receive either on-demand or continuous esomeprazole (40 mg q.d.) therapy for 88 weeks following an initial treatment by esomeprazole 40 mg daily for 8 weeks. Patients returned to the clinics for drug refilling, handled in daily symptom records, and unused esomeprazole tablets every 8 weeks.

Follow-up endoscopy with esophageal and gastric biopsies and bone density assessment were conducted at the end of 96 weeks. The major endpoint was the progression of esophageal metaplastic epithelium. The minor endpoints were (1) gastric mucosal atrophy and (2) T-score of bony mineral density.

Results: A total of 246 patients were randomly assigned to receive either on-demand (n = 125) or continuous (n =121) therapy. The on-demand group had a lower total tablet number of esomeprazole consumption than the continuous

2020 消化系聯合學術演講年會

68 group (414.0 ± 119.1 vs 667.1 ± 24.3; P < 0.001). The two patient group had had comparable histological progression rate of esophageal metaplastic epithelium at the end of 96 weeks (9.4% vs 2.2%; P = 0.105). There were no significant differences in the frequencies of mucosal atrophy over the antrum (19.5% vs 18.1%) and body (6.4% vs 9.6%) between groups (P = 0.809 and 0.608, respectively).

Additionally, the on-demand and continuous groups had comparable bone mineral densities over the lumbar spine (T-score: -0.0 ± 1.6 vs -1.0± 1.2; P = 0.846), right proximal femur (-1.0 ± 1.2 vs -1.0± 1.0; P = 0.985) and left proximal femur (-1.1 ± 1.0 vs -1.0± 1.0; P = 0.723).

Conclusions: On-demand PPI therapy is not inferior to continuous PPI therapy in the prevention of histological progression of Barrett’s esophagus. The two therapies have comparable impacts on the development of gastric mucosal atrophy and the bone mineral density in patients with Barrett’s esophagus.

內視鏡黏膜下剝離術治療 pT1a-mm / pT1b 食道癌的結果：有和無輔助治療 OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR PT1AMM/PT1B ESOPHAGEAL CANCER: WITH AND WITHOUT ADJUVANT THERAPY 1

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王靖雅 李承翰 陳博煥 李沐憲 林政輝 鄒永寬 1 長庚大學醫學院 2 林口長庚醫院胃腸肝膽科系

Background: Surgery has been the standard of care for cT1N0M0 esophageal cancer but its morbidity and mortality have consistently been the main problems.

Endoscopic submucosal resection (ESD) is a minimally invasive treatment and its use is increasing. Its application even goes beyond its absolute indications. With the addition of adjuvant therapy, some studies have reported good oncological results in patients with pT1a-M3 / pT1b esophageal cancer who are at risk of metastasis treated

by ESD. However, on the other hand, for patients with pT1a-M3 / pT1b esophageal cancer who have no risk of metastasis, any adjuvant treatment may be overtreatment.

Aims: This study is to report the treatment strategy of ESD and selective adjuvant therapy for pT1a-M3/pT1b esophageal cancer. We aim to compare the outcomes between ESD with and without adjuvant therapy.

Methods: This was a retrospective cohort study conducted in a single center. Between 2012 and 2017, 42 patients with 46 pT1a-M3/pT1b esophageal cancers proved by post-ESD pathology were enrolled in this study. All ESD procedures were performed by a single endoscopist (Tsou YK). After ESD, it was our protocol to administer adjuvant therapy for the patients with the following criteria: (1) positive vertical resection margins (a risk factor of residual tumors); (2) presence of lymphovascular invasion (LVI) in the resected specimens (a risk factor of metastasis); or (3) any cancer with SM2 or deeper invasion (a risk factor of lymph node metastasis). Twelve patients received adjuvant therapy (AT group) and 30 patients did not receive adjuvant therapy (non-AT group). Adjuvant therapy included esophagectomy (n = 5) or chemoradiotherapy (n = 7) and was at the patient’s discretion. If the patient refused adjuvant therapy, close observations were offered.

Results: All patients had an ECOG score of 0 or 1. Patient’s characteristics, including mean patient age (58.7 vs. 56 years), male gender (91.7% vs. 93.3%), and concurrent

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69 cancers (25% vs. 16.7%) were not significantly different between AT and non-AT groups. Tumor characteristics including mean tumor length (3.4 vs. 4.5 cm), a ratio of squamous cell carcinoma (100% vs. 90%), tumor location at middle esophagus (50% vs. 53.3%), and tumor involving ≥3/4 esophageal circumference (41.7% vs. 30%) were not significantly different. About the ESD results, mean procedure time (10 vs. 8.3 min/cm2 ), en bloc resection rate (91.7% vs. 100%), and complication (perforation and major bleeding) rates were not significantly different.

However, R0 resection rate (66.7% vs. 96.7%, p = 0.018) and complete resection rate (defined as R0 resection without LVI, 25% vs. 96.7%) were significantly lower in the AT group. After the ESD, pT1b-SM2 cancers (75% vs.

33.3%, p = 0.014) and poorly-differentiated cancers (75% vs. 43.3%, p = 0.063) were more prevalent in AT group.

The mean period of follow-up was 40.4 months and 41.1 months in the AT group and non-AT group, respectively.

During the follow-up, metachronous neoplasms (including high-grade dysplasia) were detected in 16.7% of patients in each group. Only one patient (3.3%) in the non-AT group had distant metastasis. The 3-year overall survival (OS) rates (82.5% vs. 81.6%) and disease-specific survival rates (100% vs. 95.8%) were not significantly different between the two groups.

Conclusions: According to the post-ESD pathology, ESD combined with adjuvant therapy could achieve good oncologic results for T1a-M3/pT1b esophageal cancer patients with risk. The outcomes were at least as well as those patients without risk. ESD and selective adjuvant therapy may be a good strategy for the treatment of T1a-M3/pT1b esophageal cancer patients but further studies may be needed to confirm.

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LMR 是造成多發性食道癌的危險因子 LOW LYMPHOCYTE TO MONOCYTE RATIO IS A RISK FACTOR FOR DEVELOPING SYNCHRONOUS ESOPHAGEAL CANCER IN PATIENTS WITH HEAD AND NECK CANCERS 陳啟仁 義大醫院 Background: Patients with head and heck squamous cell carcinoma (HNSCC) frequently developed synchronous esophageal cancers (ESCC). Some previous studies showed the defect in host anticancer immunity may predispose to multiple cancer development. The neutrophil-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR), reflect the balance between pro-cancer inflammatory and anti-cancer immune responses, but their roles in HNSCC patients and field cancerization are still uncertain Aims: Find a predictor for synchronous esophageal cancer Methods: We consecutively enrolled the patients with newdiagnosed HNSCC patients and all received pre-treatment esophageal screening at EDA Hospital. The pretreatment NLR, LMR, PLR were calculated and correlated to the clinical features Results: A total of 717 HNSCC who received esophageal screening were enrolled. One-hundred and three patients (14.4%) were found to have synchronous ESCCs, and associated with a worse overall survival (Logrank P<0.0001, Figure 1A). In univariate analysis, high NLR (4.14 vs 3.29, P=0.044) and low LMR (3.93 vs 4.99, P=0.001), but not PLR (12.35 vs 11.45, P=0.49) were significantly associated with synchronous cancer development. Using ROC curve to define the cut-off (CF) value of NLR (AUC:0.583; CF:2.5, sensitivity 60%, specificity: 52%) and LMR (AUC: 0.349; CF=4, sensitivity: 60%, specificity: 64%) to predict the presence of synchronous ESCC were shown in Figure 1B & 1C. Multivariate logistic regression showed LMR <4 (OR:2.81; 95% CI:1.55-5.09, P=0.001), low body mass index (BMI) <22 (OR: 2.22 , 95% CI: 1.35-3.64, P=0.002) and alcohol consumption (OR: 5.56; 95%CI 1.67-18.52, P=0.005) were associated synchronous ESCC (Table 1).

The patients with low-LMR also had a worse prognosis than those with high-LMR (Log-rank P<0.0001, Figure 1D).

Conclusions: Low-LMR was an independent risk factor for developing synchronous esophageal cancers and may guide the surveillance program for HNSCC patients

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有線磁控式膠囊內視鏡系統於上消化道之 操作性和可靠度研究 AN ADVANCED RESEARCH OF A WIRED MAGNETIC-ASSISTED CAPSULE ENDOSCOPE SYSTEM IN MANEUVERABILITY AND RELIABILITY FOR UPPER GASTROINTESTINAL TRACT 1

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王柏川 張瀚文 陳青富 陳重助 李晉賢 吳政輝 1 1 2 呂立達 黃士育 邱愛珍 1 新竹馬偕紀念醫院胃腸肝膽科 2 新竹馬偕紀念醫院家庭醫學科

Background: Capsule endoscope (CE) was first introduced to detect the diseases for small bowel exploration by Gavriel Iddan [1], and then it became a very popular issue to explore the upper gastrointestinal tract. However, CE can just move under gravity with body position changing to detect intragastric lesions and normal gastric anatomy.

There are mainly two active locomotion system methods: an internal locomotion system uses an embedded on-board miniaturized actuator and an external locomotion system that relies on magnetic force to control capsule movement.

Among them, magnetic-assisted CE (MACE) system has been widely applied in detecting gastric diseases, and can be used to detect focal lesions in the upper and lower stomach with comparable accuracy with conventional gastroscopy in clinical trial.The wired MACE system is a new style capsule endoscope, and the biggest difference from wireless MACE system is that wired MACE system can successfully complete the examination of the esophagus. Furthermore, because the wire connected with capsule, the esophagus can be inspected when the capsule withdrawing, and there is no risk of capsule retention.

Aims: We still doubt that the commercially available wired MACE system can manipulate CE in the proximal gastric area for different body type users by the same magnet strength. Therefore, the relationship between the operational maneuverability and different body type individuals by using standardized MACE system will be explored in this study. In addition, this study will also discuss participant’s satisfaction scores and physician’s visibility scores between different body type individuals by using wired MACE system.

Methods: In this study, BMI, waistline, lying abdominal wall thickness, the distance from abdomen wall to stomach, the distance from abdomen wall to duodenal bulb were defined as independent variables, and among them, all

numerical data will be divided into two groups by normal physiological values or sample means. The time spent from mouth to enter the duodenal bulb, satisfaction scores and visibility scores were defined as dependent variables. A total of 23 participants, will be tested between divided two groups and Mann Whitney U Test was employed Results: There were no statistically significant difference between different body type participants and the spending time to enter their duodenal bulb, and with the p-value of BMI group, waistline group, lying abdominal wall thickness group, the distance from abdomen to stomach group and the distance from abdomen to duodenum group were 0.732, 0.379, 0.934, 0.748 and 0.520, respectively.

Although MACE is slightly less maneuverability with more obese participants, which means it takes more time for capsule to enter the duodenal bulb of a thicker abdominal wall participant, however, these two variables were still not statistically significant. Most participants satisfied with MACE system. The average satisfaction scores of BMI group, waistline group, lying abdominal wall thickness group, the distance from abdomen to stomach group and the distance from abdomen to duodenum group were 7.73, 7.58, 7.76, 7.76 and 7.76, and the p-values were 0.274, 0.927, 0.702, 0.826 and 1.000, respectively. As for visibility scores, the scoring items: upper esophagus、 middle esophagus、lower esophagus、esophagealgastric junction、gastric fundus、body of stomach、 antrum、duodenal bulb、posterior bulb and second portion of duodenum had obtained nearly full score. Only the visibility score of gastric fundus was scored 77.5 points. After statistical test of visibility scores of different groups in individual variables, it was found that there was no significant difference except for the gastric fundus in different waistline groups (p-value=0.021<0.05).

Conclusions: This is the first research to investigate the relationship between magnetic force and body type by using wired MACE system. This study verified the wired MACE system can be used on everyone of different body types. Different body types do not affect the maneuverability of wired MACE system. Although it has good visibility in most upper gastrointestinal tract systems, it has not achieved good results in the gastric fundus.

However, we had discussed possible solutions and hope the wired MACE system can be developed comprehensively.

Almost all participants are satisfied with this more friendly and comfortable advanced stomach examination method, we believe that the wired MACE system will be more widely used in the field of preventive medicine.

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主題：膽胰疾病（二） 71

Galectin-3 與 S100A9：嶄新的胰臟癌誘發 糖尿病因子 GALECTIN-3 AND S100A9: NOVEL DIABETOGENIC FACTORS MEDIATING PANCREATIC CANCER–ASSOCIATED DIABETES 1,2

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廖偉智 周綠蘋 吳明賢 黃馨儀 1 國立臺灣大學醫學院 2 國立臺灣大學醫學院附設醫院

Background: Pancreatic cancer–associated diabetes (PCDM) is a paraneoplastic phenomenon accounting for 1% of new-onset diabetes and occurs in 50% of pancreatic adenocarcinoma patients within 24 months before the diagnosis of cancer. Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the U.S. and is projected to become the second leading cause of cancer deaths by 2030. Surgical resection of tumor is the only potential cure, but ;85% of patients present with unresectable tumors.

Therefore, PC is the most lethal cancer, with a 5-year survival rate of only 7.7% , underscoring the urgent need for detecting PC at an early/resectable stage.

Aims: We aimed to identify the mediators of PCDM and evaluate their usefulness in distinguishing PCDM from type 2 diabetes.

Methods: Secreted proteins of MIA PaCa-2 cells were identified by proteomics, and those with≥10fold overexpression in transcriptome analysis were assessed by bioinformatics and glucose uptake assay to identify candidate factors. Expression of factors was compared between tumors with and without PCDM by immunohistochemistry. Serum levels were measured in a training set including PC with and without PCDM, type 2 diabetes, pancreatitis, other pancreatic/peripancreatic tumors, and control subjects (n = 50 each). Cutoff values for differentiation between PCDM and type 2 diabetes from the training set were validated in a test set (n = 41 each).

Results: Galectin-3 and S100A9 were overexpressed in tumors with PCDM and dose-dependently suppressed insulin-stimulated glucose uptake in C2C12 myotubes.

In the training set, serum galectin-3 and S100A9 levels were exclusively increased in patients with PCDM and distinguished PCDM from type 2 diabetes (area under the curve [AUC] galectin-3: 0.73 [95% CI 0.64–0.83]; S100A9: 0.79 [95% CI 0.70–0.87]). Similar results were observed in the test set (AUC galectin-3: 0.83 [95% CI 0.74–0.92]; S100A9: 0.77 [95% CI 0.67–0.87]), with

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sensitivity and specificity 72.1% and 86.1%, respectively, for galectin-3 and 69.8% and 58.1% for S100A9 in differentiating between PCDM and type 2 diabetes.

Conclusions: Galectin-3 and S100A9 are overexpressed in PCDM tumors and mediate insulin resistance. Galectin-3 and S100A9 distinguish PCDM from type 2 diabetes in subjects with new-onset diabetes.

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Nanoliposomal irinotecan 合 併 fluorouracil 與 folinic acid 用於轉移性胰臟癌經健澤治 療失敗病人治療的真實世界經驗 NANOLIPOSOMAL IRINOTECAN WITH FLUOROURACIL AND FOLINIC ACID IN METASTATIC PANCREATIC CANCER AFTER PREVIOUS GEMCITABINEBASED THERAPY: A REAL WORLD EXPERIENCE

內視鏡超音波導引 (EUS-guided) 下的胰臟 和 非 胰 臟 病 灶 組 織 切 片 - FNA needles 和 FNB needles (Procore, Boston Acquire) 兩者 間使用後的心得和比較 - 一個區域教學醫院 的臨床經驗分享 THE COMPARISON OF ENDOSCOPIC ULTRASOUND(EUS)-GUIDED TISSUE ACQUISITION USING FINE NEEDLE ASPIRATION(FNA) NEEDLES AND FINE NEEDLE BIOPSY(FNB) NEEDLES(PROCORE, BOSTON ACQUIRE)FOR PANCREATIC AND NONPANCREATIC LESIONS - A CLINICAL EXPERIENCE FROM A REGIONAL TEACHING HOSPITAL IN SOUTHERN TAIWAN

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于洪元 李重賓 趙毅 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學院 Background: Nanoliposomal irinotecan (nal-IRI) is an effective and safe therapy, accompanied with 5-fluorouracil (5-FU) and leucovorin (LV), for metastatic pancreatic ductal adenocarcinoma whose disease progressed after gemcitabine-based chemotherapy. In NAPOLI-1 study, this regimen showed survival benefit, compared to 5-FU and LV therapy, and was proved by FDA. Aims: To evaluate the effectiveness and safety of nal-IRI + 5-FU/LV regimen, prescribed to the patients with metastatic pancreatic cancer and gemcitabine-based treatment failure in the real world.

Methods: We retrospectively collected the data of the patients with metastatic pancreatic adenocarcinoma who had a gemcitabine-based treatment failure and were treated by nal-IRI-based regimen in Taipei Veteran General Hospital.

Results: From August, 2018 to June, 2019, sixty-seven patients who received nal-IRI + 5-FU/LV regimen were identified. The median age: 65 years-old, male sex: 52%.

ECOG performance status 0-2. The median initial dose of nal-IRI was 36.8 mg/m 2 and the dose intensity was 106.5 mg/m2 within 6 weeks. The median overall survival was 4.8 months (95% confidence interval (CI): 3.3 – 6.4 ) and median progression-free survival was 2.4 months (95% CI: 1.3 – 3.6 ). Six-month OS and PFS rates were 42% and 22%. Objective response and disease control rates were 10.4% and 38.8%. Among the patients, only 41 patients met the inclusion criteria of NAPOLI-1 study (ECOG 0-1, normal renal and liver function). The median overall survival (6.33 months) became consistent with the NAPOLI-1. The most common all grade adverse effects were anemia (73.9%), nausea (66.2%) and fatigue (61.5%).

Most common grades 3-4 adverse effects were neutropenia (21.5%), anemia (18.5%) and diarrhea(15.4%).

Conclusions: In the real-world, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma that progressed after gemcitabine-based therapy.

林成業 王嗣仁 曾逸豪 陳錫榮 蔡青陽 孫盟舜 高雄市阮綜合醫療社團法人阮綜合醫院消化內科 Background: Endoscopic Ultrasound(EUS)-guided tissue acquisition using Fine needle Aspiration(FNA) needles(Cook Echotip, Olympus)has been widely used as the standard criterion for the diagnosis of both Pancreatic and Non-Pancreatic lesions(adjacent to the gastrointestinal tract) in our institution since 2004. As we all know, the definite diagnosis of lesion relies on immunohistochemical staining, which depends on adequate tissue being submitted to the pathologist. And for the reasons that advancements in needle design and improvement of tissue acquisition may improve the definite diagnosis of lesions we approached, our physicians were alternatively using FNB needles(Procore, Boston acquire) for tissue acquisition since 2017.In this study, we aimed to compare the diagnostic yield of both Pancreatic and Non-Pancreatic lesions under EUS-guided tissue acquisition using FNA needles and FNB needles(Procore, Boston Acquire) Aims: The goals of this study are 1) to compare the overall diagnostic yield(DY) of EUS-guided tissue acquisition using FNA needles and FNB needles(Procore, Boston acquire); 2)to compare the diagnostic yield(DY) of EUSguided tissue acquisition using FNA needles and FNB needles for isolated Pancreatic and Non-Pancreatic lesions Methods: We retrospectively reviewed 101 patients who underwent EUS-guided tissue acquisition using FNA needles or FNB needles(Procore, Boston Acquire) for Pancreatic/Non-Pancreatic lesions at our institution over 3 years, from January 2017 to December 2019.

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2020 消化系聯合學術演講年會

74 Demographics(age, gender), lesion characteristics(size, locations), size of needle used, numbers of passes and the diagnostic yield(DY)were compared between the FNA needles and FNB needles(Procore,Boston Acquire)groups.

The statistical analyses was perfomed using Chi-square test and unpaired student test.

Results: A total of 101 patients(54 men, mean age 63.4years) underwent EUS-guided FNA/FNB were reviewed. The needle size most often used was 22 gauge in both FNA needle and FNB needle groups.The average size of the lesions using FNA needles and FNB needles were 33.5mm and 33.8mm respectively. About 66% lesions were located at Pancreas, 75 patients underwent EUS-guided tissue acquisition using FNA needles and 26 patients using FNB needles(Procore, Boston Acquire).The overall diagnostic yield of FNA needles and FNB needles were 77% and 85%,the diagnostic yield for Pancreatic lesions using FNA needles and FNB needles were 81% and 88%, and the diagnostic yield for Non-Pancreativc lesions using FNA needles and FNB needles were 70% and 80% respectively.

Conclusions: In this study,there was no significant difference between the two groups(FNA needles and FNB needles) regarding to demographics and lesion characteristics. However, the overall diagnostic yield(DY) of EUS-guided tissue acquisition using Fine needle Biopsy(FNB) needles was slightly higher, compared to FNA needles (85% vs 77%), and the superiority of FNB needles to FNA needles remained unchanged in both isolated Pancreatic lesions(88% vs 81%) and NonPancreatic lesions(80% vs 70%).

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門冬醯胺酶之單位時間劑量與兒童急性淋 巴性白血病病人發生胰臟炎之相關性研究 DOSE INTENSITY OF L-ASPARAGINASE CORRELATES WITH INCIDENCE OF PANCREATITIS, RATHER THAN ACCUMULATED DOSE: A RETROSPECTIVE OBSERVATIONAL STUDY OF PEDIATRIC ALL PATIENTS IN A TERTIARY CENTER 1

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陳其柏 張修豪 周書緯 楊永立 盧孟佑 周獻堂 1 1 1 陳慧玲 倪衍玄 吳嘉峯 1 臺灣大學醫學院附設醫院兒童醫院小兒肝膽腸胃科 2 臺灣大學醫學院附設醫院兒童醫院小兒血液腫瘤科 Background: L-Asparaginase (L-Asp) is an important anti-leukemic agent in the management of pediatric acute lymphoblastic leukemia (ALL). Asparaginase-associated pancreatitis (AAP) is a well known complication, causing cessation of L-Asp and the postpone of treatment schedule.

Premature cessation of L-Asp may relate to inferior eventfree survival, especially in early CNS relapse in pediatric ALL. Aims: The study is aimed to investigate the role of L-Asp dosage in inducing AAP, and the related risk factors of AAP in ALL children.

Methods: A total of 353 ALL children were enrolled from a tertiary medical center in Taiwan between 2002 and 2019.

These patients were treated by TPOG 2002 or TPOG 2013 protocol accordingly. The data of clinical characteristics (age, sex, timing of developing AAP), treatment protocol, dose regimen of L-Asp and clinical outcomes were collected from medical chart and the Taiwan Pediatric Oncology Group registry. We defined the intensity of L-Asp as the maximal dosage that patient would receive throughout the treatment protocol. These data were analyzed to identify the risk factors of AAP. Results: In this cohort, 14/353 (4.0%) of ALL patient developed AAP. AAP was diagnosed during induction in 9 (64.3%) patients and re-induction in 5 (35.7%) patients.

Both induction and re-induction courses consisted the most intensive L-Asp injection protocol. We discovered that the age at diagnosis (>6.8 years of age) and the dose intensity of L-Asp were the most significant risk factors of AAP in multivariate analysis. Considering the cumulative dose and the maximal intensity of L-Asp in the statistic model, only the L-Asp intensity showed a linear relationship correlates with incidence of AAP in this study.

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75 Conclusions: The L-Asp intensity correlates with incidence of AAP in our pediatric ALL cohort. Our study provided a possible explanation of the clustered fashion of AAP during induction and re-induction in pediatric ALL patients.

肝纖維化掃描儀於膽汁滯留症嬰兒診斷膽 道閉鎖之成效探討：追蹤性研究 DIAGNOSTIC PERFORMANCE OF TRANSIENT ELASTOGRAPHY IN BILIARY ATRESIA AMONG CHOLESTASIS INFANTS: A FOLLOW UP STUDY 1

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巫韻安 張美惠 鄭永銘 陳慧玲 倪衍玄 許宏遠 1 吳嘉峯 1 國立臺灣大學附設醫院小兒部 2 國立臺灣大學附設醫院病理部 3 國立臺灣大學附設醫院肝炎研究中心

1

Background: Biliary atresia (BA) is a rare and challenging disease in infants. Early detection of BA is important for successful treatment and a favorable prognosis.

Aims: This follow-up study aimed to confirm the diagnostic performance of transient elastography with liver stiffness measurement (LSM) >7.7 kPa in BA among cholestasis infants.

Methods: Sixty-one cholestatic infants (5-121 days of age) with direct bilirubin level >1 mg/dL were enrolled in this follow-up study. Liver biopsy was performed in 31 subjects, and Picro Sirius red staining was applied to assess quantitative estimations of collagen fibers in these liver specimens. We used transient elastography to assess the LSM during the cholestatic workup in these 61 cholestatic infants, and 15 were diagnosed as BA. We analyzed the positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for BA in cholestatic infants with LSM > 7.7 kPa. Results: Significant positive correlation between LSM and the percentage of collagen fibers stained by Picro Sirius red was demonstrated in this cohort (p= 0.027). An LSM > 7.7 kPa transient elastography cut-off provided the best accuracy for the diagnosis of significant fibrosis in BA population. The PPV, NPV and diagnostic accuracy for LSM > 7.7 kPa in predicting BA were 92.3%, 93.8%, and 92.4%, respectively, among cholestatic infants.

Conclusions: Transient elastography is a non-invasive technique in the diagnostic evaluation of cholestatic infants. LSM is positively correlate with the status of liver fibrosis stained by Picro Sirius red in liver specimens from cholestatic infants. We comfirmed that an LSM> 7.7 kPa has high PPV, NPV, and diagnostic accuracy to differentiate BA from other non-BA cholestatic infants.

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壁報展示

第一部分：肝 P.001 Telbivudine 改善 B 型肝炎帶原之癌症病患 接受全身性化療後之腎功能 TELBIVUDINE IMPROVES RENAL FUNCTION IN HBV CARRIERS WITH MALIGNANCY RECEIVING SYSTEMIC CHEMOTHERAPY 1

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黃上秦 蘇東弘 劉俊人 曾岱宗 廖思涵 1, 2, 3 1, 4 高嘉宏 楊宏志 1 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科 2 國立臺灣大學醫學院附設醫院肝炎研究中心 3 國立臺灣大學醫學院臨床醫學研究所 4 國立臺灣大學醫學院微生物學科暨研究所 Background: Prior studies have demonstrated the efficacy of telbivudine in improvement of renal function in chronic hepatitis B patients. Pre-emptive prophylaxis is strongly recommended for HBV carriers with malignancy receiving systemic chemotherapy. However, limited data is available about the effect of prophylactic telbivudine on renal function in these patients.

Aims: This study aimed to investigate the renoprotective effect of prophylactic telbivudine in HBV carriers with malignancy receiving cytotoxic chemotherapy. The clinical effectiveness and safety of prophylactic telbivudine will be also analyzed.

Methods: From 1 st January 2015 to 31 st December 2016, 165 HBV carriers with cancer receiving systemic chemotherapy and prophylactic telbivudine or entecavir in the hepatologic clinic of National Taiwan University Hospital were enrolled. We compared the change in eGFR, adverse events, drug resistance and reactivation of HBV between telbivudine and entecavir groups.

Results: One hundred and twenty-seven patients received telbivudine and 38 patients received entecavir as prophylaxis against HBV reactivation. No significant difference was observed in gender, age, BMI, comorbidity of DM and mean follow-up duration of the two groups. In the median interval of 29.3 months, eGFR improvement, calculated by Cockcroft-Gault Equation, was significantly higher in patients receiving prophylactic telbivudine than those receiving entecavir (+4.23 and -14.61 mL/min/1.73 m2, p < 0.001), regardless of the time after stopping the anti-viral agents. In the median follow-up duration of 39.8 months, the adverse events were significantly more frequent in telbivudine group (19.69%, all non-fatal, mainly elevated CK), while the drug resistance and reactivation rates of HBV were not significantly different.

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Conclusions: Telbivudine improves renal function in HBV carriers with malignancy receiving systemic chemotherapy, with equal efficacy and more non-fatal adverse events compared to entecavir.

2020 消化系聯合學術演講年會

P.002

P.003

B 型肝炎肝移植術後從 Tenofovir Disoproxil Fumarate 轉換至 Tenofovir Alafenamide 的 療效

以口服核苷酸類似物治療慢性 B 型肝炎停 藥後臨床復發再治療 - 藥物持久性差異之探 討 OFF-TREATMENT DURABILITY OF ANTIVIRAL RESPONSE TO NUCLEOS(T)IDE ANALOGUES THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B

CONVERTING FROM TENOFOVIR DISOPROXIL FUMARATE TO TENOFOVIR ALAFENAMIDE IN PATIENTS WITH HEPATITIS B FOLLOWING LIVER TRANSPLANTATION 1

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鄭志軒 洪豪謙 李勁樵 王瑜肇 吳宗翰 李正方 1 1 1 2 1 吳庭榕 周宏學 詹昆明 李青松 李威震 1 林口長庚紀念醫院一般外科 2 林口長庚紀念醫院胃腸肝膽科

Background: Taiwan has a high prevalence of hepatitis B (HBV) and HBV related end-stages liver diseases are the leading causes of liver transplantation (LT). Tenofovir alafenamide (TAF) is a recently approved agent for the treatment of chronic HBV and has demonstrated improved renal profiles compared with tenofovir disoproxil fumarate (TDF) in multinational phase III trials. The aim of this study was to assess the outcomes of TAF treatment in LT recipients.

Aims: The aim of this study was to assess the outcomes of TAF treatment in LT recipients.

Methods: This retrospective study analyzed 23 LT patients who received treatment with TDF and TAF at a single reference center. Change from baseline in renal function were compared.

Results: At Chang Gung Memorial Hospital Linkou, 23 LT recipients received TDF for ≥ 48 weeks and switched to TAF. 14 patients received living donor LT, 7 patients deceased whole LT and 2 patients split LT. At the time of transplantation, median Model of End-Stage Liver Disease (MELD) score was 20 (interquartile range, IQR 10-27). Median duration of treatment with TDF was 1114 days (range 84-2141). During treatment with TDF, eGFR (Modification of Diet in Renal Disease, MDRD) significantly decreased at weeks 24 and 48 (mean level 12.71 ± 23.36 and 15.13 ± 15.79 mL/min/1.73m 2 for week 24 and 48, p=0.016 and <0.001 respectively).

After switching to TAF, at week 24, mean eGFRMDRD change was 5.96 ± 11.62 mL/min/1.73m2, p=0.029. Before conversion to TAF, 7 patients remained HBsAg positive after transplantation and 4 patients experienced HBV reactivation. One patient became HBsAg negative 52 weeks after treatment. No patients discontinued TDF or TAF due to side effects.

Conclusions: Converting from TDF to TAF led to significant early improvement in renal function.

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文士祺 郭武憲 鄭隆致 柯朝元 蔡奇璋 黃健維 1 屏東寶建醫院醫療部胃腸肝膽科 2 彰化員林員生醫院 3 高雄國軍高雄醫院醫療部內科部胃腸肝膽科

Background: Recent studies indicated high virological relapse rates ranging from 40% to 95% in the first year after neocleos(t)ide analogue (NUC) cessation.

Aims: We investigated off-treatment durability after NUC cessation in patients with chronic hepatitis B in PingTung County. We aimed to ascertain predictive factors for clinical relapse and subsequent retreatment.

Methods: We conducted a retrospective study. A total of 34 consecutive retreatment patients (18 HBeAg-negative and 16 HBeAg-positive) who received entecavir (ETV) (n=17) and tenofovir (TDF) (n ＝ 17) were followed up for approximately 120 months. Baseline characteristics were examined to identify factors associated with retreatment.

Results: The rate of clinical relapse for retreatment was 55.7% (34/61). Patients discontinuing TDF exhibited significantly higher rates of clinical relapse for subsequent retreatment occurring mostly within 18 months than those discontinuing ETV (94.1% vs. 47.1%, P ＝ 0.003). Cox regression analysis revealed factor with TDF therapy was most predictive for retreatment within 18 months (HR: 2.839; 95% CI: 1.055-7.639; P ＝ 0.039).

Conclusions: Almost half of the patients had clinical relapse for subsequent retreatment after cessation of NUC therapy. Discontinuation of TDF treatment rather than EVT treatment is associated with earlier clinical relapse for retreatment. NUC-specific post-therapy monitor is necessary.

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P.004

P.005

Entecavir 與 tenofovir 治療台灣慢性 B 型肝 炎病人之肝癌風險 RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS TREATED WITH ENTECAVIR VS TENOFOVIR FOR CHRONIC HEPATITIS B IN TAIWAN

慢性 B 型肝炎患者的 A 型與 D 型肝炎感染 與晚期肝病相關 BOTH HEPATITIS A AND HEPATITIS D INFECTION MAY BE ASSOCIATED WITH MORE ADVANCED LIVER DISEASE IN PATIENTS WITH CHRONIC HEPATITIS B

1,2,3,4,5

4,5

1,2

1,2

1,2

高偉育 蘇建維 張甄 唐瑞祥 張君照 1 臺北醫學大學附設醫院內科部胃腸科 2 臺北醫學大學醫學院內科學科 3 臺北醫學大學臨床醫學研究所 4 臺北榮民總醫院內科部胃腸科 5 陽明大學醫學院醫學系

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 compare ETV and TDF in terms of the risk of HCC in patients with CHB. Methods: We performed a retrospective cohort study from 2012 to 2016. Treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from one academic teaching hospital. Cumulative incidences of HCC were assessed.

Results: In total, 160 patients (80 and 80 in the ETV and TDF groups, respectively) were recruited. TDF-treated patients were younger age, had higher HBV DNA and platelet count, lower bilirubin and fibrosis index based on four factors, lower portion of cirrhosis and diabetes than ETV-treated patients. The HCC incidence was not statistically different between the ETV and TDF groups (P = 0.225). Multivariate analysis yielded cirrhosis (Hazard ratio, 8.746; 95% confidence interval, 2.227-34.345; P = 0.002) and Child-Pugh score (Hazard ratio, 1.746; 95% confidence interval, 1.260-2.419; P = 0.001) were the independent factors associated with higher risk of HCC. Conclusions: There was no difference in terms of the risk of HCC in patients with CHB receiving ETV or TDF. Further large cohort long-term effects of antiviral agents for CHB studies are warranted.

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1

1,2

1,2,4

1,2

1,2

吳哲瑋 曾岱宗 劉俊人 蘇東弘 劉振驊 1,2,4 1,2,4,5 1,2,3,4 陳培哲 陳定信 高嘉宏 1 國立臺灣大學醫學院附設醫院腸胃肝膽內科 2 國立臺灣大學醫學院附設醫院肝炎研究中心 3 國立臺灣大學醫學院附設醫院醫學研究部 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

Background: Acute infection of hepatitis A virus (HAV) causes transient but varying degrees of liver damage. In contrast, hepatitis D virus (HDV) only infects patients with chronic hepatitis B virus (HBV) infection, which may cause chronic and persistent liver damage.

Aims: We aimed to explore whether infection of both hepatropic virus was associated with worse outcomes in patients with chronic HBV infection in a cross-sectional study.

Methods: We collected serum and clinical data from 464 patients with chronic HBV infection, including 160, 150 and 154 patients with hepatocellular carcinoma (HCC), cirrhosis and inactive carrier status, respectively. Serum HAV-IgG and HDV-IgG were determined retrospectively and seroprevalence rates of both markers were compared among the groups with different clinical stages.

Results: In the inactive carrier group, 106 (68.83%) and 3 (1.95%) patients had exposure to HAV and HDV infection, respectively. We found higher seropositive rates of HAVIgG in cirrhosis (82.67%) and HCC (99.38%) groups, but not seropositive rates of anti-HDV (4.67% and 3.75% for cirrhosis and HCC respectively). When combining cirrhosis and HCC groups as patients with advanced liver disease, seropositive HAV and HDV were associated with increased risks of advanced liver disease with odds ratio of 15.69 (95% CI: 3.25-75.68, p<0.001) and 12.41 (95% CI: 1.40109.95, p<0.05), respectively.

Conclusions: In the cross-sectional case-control study of patients with chronic HBV infection, both exposure to HAV or HDV infection might be associated with an increased risk of cirrhosis and HCC development.

2020 消化系聯合學術演講年會

P.006

P.007

血漿人類 C 型凝集素 18 在慢性 B 型肝炎感 染不同時期之表現 THE PLASMA HUMAN C-TYPE LECTIN 18 LEVELS AT DIFFERENT PHASES OF CHRONIC HEPATITIS B VIRUS INFECTION

接受化療的慢性 B 型肝炎病患使用核苷酸 類似物預防 B 型肝炎病毒活化具有好成效 及低臨床復發：單一醫學中心使用經驗 GOOD EFFICACY AND LOW CLINICAL RELAPSE OF HEPATITIS B VIRUS REACTIVATION WITH NUCLEOS(T) IDE ANALOGUES PROPHYLAXIS IN CHRONIC HEPATITIS B PATIENT UNDER CHEMOTHERAPY : A SINGLE– CENTER REAL-WORLD EXPERIENCE

蔡宗佑 彭成元 中國醫藥大學附設醫院消化系中心 Background: C-type lectin 18 (CLEC18) is a novel glycoprotein which is highly expressed in liver and immune cells. We previously demonstrated that CLEC18 was downregulated by HBV infection. Baseline plasma CLEC18 levels can predict HBeAg loss, HBeAg seroconversion and virological response in patients with HBeAg-positive chronic hepatitis B (CHB) receiving nucleos(t)ide analogue (NUC) therapy. However, the plasma CLEC18 levels during the natural course of CHB are unknown.

Aims: To investigate the plasma CLEC18 levels at different phases of CHB. Methods: We retrospectively enrolled a cohort of patients at different phases of CHB, including immune tolerance phase (n=12), immune clearance phase (n=10), HBeAg-positive CHB with acute exacerbation (n=15), HBeAg-positive CHB with acute exacerbation and liver decompensation (n=10), CHB with recent spontaneous HBeAg seroconversion (n=18), inactive residual phase, HBeAg-negative reactivation phase (n=21), and CHB with spontaneous HBsAg seroconversion (n=7). The plasma CLEC18 levels were measured using a home-made ELISA kit Results: The plasma CLEC18 levels were 265.1±20.10 (mean±standard error), 587.8±320.9, 275.4±33.51, 252.4±73.47, 808.2±290, 718.4±257.3, 925.5±341.4, and 2831±1518 pg/mL in immune tolerance phase, immune clearance phase, HBeAg-positive CHB with acute exacerbation, HBeAg-positive CHB with acute exacerbation and liver decompensation, CHB with recent spontaneous HBeAg seroconversion, inactive residual phase, HBeAg-negative reactivation phase, and CHB with spontaneous HBsAg seroconversion, respectively. The plasma CLEC18 levels tended to be higher at CHB with recent HBeAg seroconversion (p=0.063) and inactive residual phase (p=0.076), and were significantly higher at CHB with HBsAg seroconversion phase (p=0.037) compared to those at immune tolerance phase.

Conclusions: We demonstrated that the plasma CLEC18 levels increased at HBeAg seroconversion, inactive residual phase, and after HBsAg seroconversion. Further study on the relationship between viral load and CLEC18 level is warranted.

陳永發 吳明順 陳俊男 張智翔 姚振榮 粟發滿 連吉時 臺北市立萬芳醫院消化內科 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. So Taiwan Bureau of National Health Insurance (BNHI) support the prophylactic regimen since Nov 2009 ( 1 week prior to beginning chemotherapy, and lasted 6 months after the end of chemotherapy).

Aims: To reveal the efficacy of NUCs prophylaxis during chemotherapy and clinical relapse post off NUCs prophylaxis under the guideline of Taiwan BNHI since Nov 2009.

Methods: From Nov 2009 to Jul 2018, total 207 chronic hepatitis B (CHB) patients accepted chemotherapy were included. Excluded criteria were primary liver tumor, NUCs use before or after chemotherapy, lose of follow up, lack of important data and transfer. Finally 153 patients were recruited into this study.

Results: The 153 patient cohort included 68 men and 85 women with a median age of 57.3 (28~91) years old at entry. 150 (98%) and 10 (6.5%) patients were negative Hbs Ag and liver cirrhosis. 137(89.5%) and 15(9.5%) patients had solid tumor and were treated with regimen containing Rituximab. The baseline HBV DNA level of 29(19.0%), 67(43.8%), 46(30.1%) and 11(7.2%) patients were undetectable, < 2000 IU/ml, 2000~106 IU/ml and >106 IU/ ml, respectively. 140 (91.5%) patients were treated with high genetic barrier NUCs. The period of chemotherapy and NUCs consolidation were 8.6±10.2 months and 4.66±2.75 months. 23 patients had ALT>2xULN during chemotherapy, and the causes included liver metastasis:3, sepsis:9 and chemotherapy : 11. No one of flare up was due to HBV reactivation under NUCs prophylaxis. 51 patients died in periods of chemotherapy and NUCs consolidation,

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P.008 finally 102 patients were recruited into subgroup analysis with a period of 17.48±7.42 months follow up. 6 (5.9%) patients developed clinical relapse due to HBV reactivation after off NUCs prophylaxis. 5 patients relapsed within 9 months and 1 patient developed liver decompensation. Two patients were retreated with NUCs without mortality. The age, gender, cirrhosis, tumor type, NUCs type, duration of chemotherapy and consolidation had no significantly difference between nonrelapse and relapse. But the baseline HBV DNA level (log IU/ml : 2.59±1.61 vs 5.50±1.57 ), baseline ALT level >1X ULN(4.2% vs 33.3%) and Rituximab use (11.5% vs 50.0%) had strongly significantly difference (p<0.01) between nonrelapse and relapse. We used relapse as dependent variable and baseline HBV DNA level (log IU/ml), baseline ALT level >1X ULN and Rituximab use as independent variables. Multivariate logistic regression models showed baseline HBV DNA level (OR: 3.373 , 95% CI: 1.462 –7.783 , P= 0.004) and Rituximab use (OR: 15.745 , 95% CI: 1.086 –228.356 , P= 0.043) remained significantly related to the presence of relapse.

Conclusions: From our limited study, no HBV reactivation related hepatitis flare up was noted during NUCs prophylaxis and less than 6 % of clinical relapse was found off NUCs prophylaxis. No mortality was noted during hepatitis flare up. We found that baseline HBV DNA level and Rituximab use were significant factors for clinical relapse. To reduce clinical relapse of patients with high risks, prolong NUCs consolidation may be worthy to further research in the future.

在有使用 TDF 風險因子的慢性 B 型肝炎病 人 從 Tenofovir Disoproxil Fumarate(TDF) 轉換至 Tenofovir Alafenamide(TAF)48 週時 之療效與安全性 SAFETY AND EFFICACY AT 48 WEEKS AFTER SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIR ALAFENAMIDE (TAF) IN CHRONIC HBV PATIENTS WITH RISK FACTORS FOR TDF USE 1

2

3

Jia-Horng Kao , Maria Buti , Pietro Lampertico , 4 5 6 Young-Suk Lim , Kosh Agarwal , Scott Fung , 7 8 Tak Yin Owen Tsang , Magdy Elkhashab , 9 10 Jose Luis Calleja Panero , Mandana Khalili , 11 12 12 Natarajan Ravendhran , Susanna Tan , John F Flaherty , 12 12 13 Anuj Gaggar , George Wu , Hie-Won Hann , 14 15 16 Calvin Pan , Hyung Jun Kim , Patrick Kennedy , 17 Henry Lik-Yuen Chan Graduate Institute of Clinical Medicine, National Taiwan 1 University College of Medicine, Taipei, Taiwan Hospital Universitario Vall d’ Hebron and Centro de Investigación Biomédica en Red de Enfermedades 2 Hepáticas y Digestivas, Barcelona, Spain Fondazione IRCCS Ca’ Granda Ospedale Maggiore 3 Policlinico, Università degli Studi di Milano, Italy Asan Medical Center, University of Ulsan College of 4 Medicine, Seoul, Republic of Korea Institute of Liver Studies, King’s College Hospital, 5 London, UK Toronto Centre for Liver Disease, Toronto General 6 Hospital, Toronto, Ontario, Canada 7 Princess Margaret Hospital, Hong Kong 8 Toronto Liver Centre, Toronto Hospital Universitario Puerta de Hierro–Majadahonda, 9 Spain 10 University of California San Francisco 11 Digestive Disease Associates, Catonsville, MD 12 Gilead Sciences, Inc., Foster City, CA 13 Thomas Jefferson University Hospital, Philadelphia, PA 14 Flushing, NY 15 Chung-Ang University College of Medicine, Seoul 16 Barts Health NHS Trust, London 17 The Chinese University of Hong Kong Background: TAF, a novel tenofovir prodrug, has demonstrated noninferior efficacy to tenofovir disoproxil fumarate (TDF) with a superior bone and renal safety

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P.009 profile through 96 weeks in viremic CHB patients and through 48 weeks in virally suppressed patients who switched to TAF from TDF. TAF is a preferred treatment in the most recent EASL and AASLD HBV Guidelines, especially in patients with risk factors for TDF-associated renal and bone effects.

Aims: We assessed safety and efficacy in virally suppressed CHB patients with TDF risk factors (RF) who were switched from TDF to TAF. Methods: In a double-blind, active-controlled, Phase 3 study, 488 CHB patients who were virologically suppressed on TDF were randomized (1:1) to switch to TAF or continue TDF for 48 weeks. Renal (serum creatinine [sCr], eGFR by Cockcroft-Gault [eGFRCG] and urine biomarkers of tubular function) and bone (serial DXA scans at hip/ spine and serum bone biomarkers) safety parameters, antiviral efficacy (HBV DNA <20 IU/mL), and ALT normalization were assessed in the subset of patients having baseline RF for TDF: Age >60 yr, osteoporosis of hip/spine, ≥Stage 2 chronic kidney disease (CKD), albuminuria (UACR >30 mg/g), hypophosphatemia (PO4 <2.5 mg/dL), or comorbidities associated with CKD (e.g.

HTN, DM, obesity).

Results: Of 488 patients randomized and treated, 358 (73%) had at least 1 RF, while 192 (39%) patients had >= 2 RF present at baseline. Baseline demographics of patients with at least 1 RF were similar between both treatment groups: 30% with age >60 years, 66% male, 80% Asian, 71% HBeAg-negative, median eGFRCG 84 mL/min, and 4% and 16% had osteoporosis at hip and spine, respectively.

Renal and bone safety results at Week 48 are summarized in the table. At Week 48, TDF patients switched to TAF showed improvements in renal (sCr, eGFRCG) parameters.

Improvements in hip and spine BMD were seen at 48 weeks following switch. Antiviral efficacy was maintained in both groups (HBV DNA <20 IU/mL: TAF 96.7% vs TDF 96.6%, p=0.96) and TDF patients switching to TAF had similar rates of normal ALT, and similar serological responses at Week 48.

Conclusions: CHB patients with risk factors for TDF toxicity who are switched from TDF to TAF show improved bone and renal safety parameters while efficacy was maintained at 48 weeks.

在病毒抑制之肝功能不全的慢性 B 肝病 人 從 TDF 或 其 他 口 服 抗 病 毒 藥 物 轉 換 至 TAF：第二期開放性臨床試驗 24 週的療效 與安全性 SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) OR OTHER ORAL ANTIVIRAL THERAPY (OAV) TO TENOFOVIR ALAFENAMIDE (TAF) IN VIRALLY SUPPRESSED CHRONIC HEPATITIS B (CHB) PATIENTS WITH HEPATIC IMPAIRMENT: WEEK 24 EFFICACY AND SAFETY RESULTS FROM A PHASE 2 OPEN-LABEL STUDY 1

2

3

Wan-Long Chuang , Young-Suk Lim , Pietro Lampertico , 4 5 6 7 Ho Bae , Jeong Heo , Yi-Hsiang Huang , Aric Josun Hui , 8 9 10 Chun-Yen Lin , Claire Fournier , Chien-Hung Chen , 11 11 11 John F Flaherty , Anuj Gaggar , Audrey Lau , 11 11 11 Shuyuan Mo , Vithika Suri , G Mani Subramanian , 12 13 14 Huy Trinh , Tak Yin Owen Tsang , Stephen Ryder , 15 Harry LA Janssen Kaohsiung Medical University Chung-Ho Memorial 1 Hospital, Kaohsiung City, Taiwan Asan Medical Center, University of Ulsan College of 2 Medicine, Seoul, Republic of Korea Fondazione IRCCS Ca’ Granda Ospedale Maggiore 3 Policlinico, Università degli Studi di Milano, Italy Asian Pacific Liver Center, St. Vincent Medical Center, Los 4 Angeles, CA Research Institute of Medical Science, Pusan National 5 University Hospital, Busan-si, Republic of Korea 6 Taipei Veterans General Hospital, Taipei, Taiwan 7 Alice Ho Miu Ling Nethersole Hospital, Hong Kong Chang Gung University College of Medicine, Taoyuan City, 8 Taiwan Hépatologie, Centre Hospitalier de l’Université de Montréal, 9 Québec, Canada Kaohsiung Chang Gung Memorial Hospital and Chang 10 Gung University College of Medicine, Kaohsiung City 11 Gilead Sciences, Inc., Foster City, CA 12 San Jose Gastroenterology, San Jose, CA 13 Princess Margaret Hospital, Hong Kong NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of 14 Nottingham, UK Toronto Centre for Liver Disease, Toronto General Hospital, 15 University Health Network, Toronto, Ontario, Canada

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P.010 Background: TAF, a novel tenofovir (TFV) prodrug, has greater plasma stability, more targeted delivery of TFV to hepatocytes, and reduced circulating levels of TFV compared to TDF. Similar efficacy to TDF with improved renal and bone safety has been demonstrated for TAF in patients with compensated liver disease.

Aims: We evaluated efficacy and safety when virally suppressed CHB patients with hepatic impairment were switched to TAF. Methods: In this Phase 2 study (NCT03180619) CHB patients with a Child Turcotte Pugh (CTP) score of >= 7 and <= 12 at screening (or past history of CTP >= 7 and any score <= 12 at screening) who were taking TDF and/ or other OAVs for >= 48 weeks, with HBV DNA <LLOQ for >= 24 weeks and <20 IU/mL at screening were eligible.

All patients were switched to TAF 25 mg QD and treated for 96 weeks. The co-primary endpoints were proportion with HBV DNA <20 IU/mL and graded adverse events (AEs)/lab abnormalities at Week 24. Key secondary safety endpoints were change in hip and spine bone mineral density (BMD), and in estimated creatinine clearance by Cockcroft-Gault (eGFRCG). Markers of bone turnover and renal tubular function were also serially assessed.

Results: 31 patients were enrolled at 18 sites in 7 countries.

At baseline, 19 (61%), 9 (29%) and 3 (10%) were CTP Class A, B, or C, respectively. Median age was 57 y (19% >= 65 y), 68% male, 81% Asian, 90% HBeAg-negative, median fibrotest score 0.81, and median eGFRCG 98 mL/ min; up to 48% had low BMD at hip and/or spine, and 68% had prior TDF exposure. Key efficacy/safety results at Week 24 are summarized in the Table. All patients had HBV DNA <20 IU/mL and a high proportion had normal ALT. Switching to TAF resulted in increases in hip/spine BMD, decreases in bone turnover markers, an increase in eGFRCG with decreases in tubular markers. TAF was well tolerated with few having Grade 3 or 4 AEs (2 patients); no serious AEs related to study drug and no discontinuations for and AE. Conclusions: In CHB patients with hepatic impairment switched to TAF from TDF or other OAVs, viral suppression was well maintained and improved bone and renal safety was seen at Week 24.

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E 抗原陽性之慢性 B 型肝炎病人 B 型肝炎發 作時使用核苷 ( 酸 ) 類似物有較低的 B 型肝 炎 E 抗原消失率—一個傾向評分匹配研究 NUCLEOS(T)IDE ANALOGUE THERAPY DECREASE THE HBEAG LOSS RATE IN HBEAG POSITIVE CHRONIC HEPATITIS B PATIENT WITH HEPATITIS FLARE: A PROPENSITY SCORE MATCHED STUDY 1,2

1,2

1,2,3

彭建維 鄭文睿 陳益程 簡榮南 1 林口長庚醫院胃腸肝膽科系 2 長庚大學醫學院 3 林口長庚醫院肝臟研究中心

1,2,3

廖運範

2,3

Background: Asian pacific guidelines have recommended that HBeAg positive patients with hepatitis flare deserve 3 months close monitoring for spontaneous HBeAg loss if there is no concerns for hepatic decompensation (Liaw YF et al. Hepat Int 2012). In contrast to earlier findings during lamivudine therapy (56%/62 vs. 25%/28, Perrillo RP et al, Hepatology 2002), a recent study involving 51 patients showed lower HBeAg loss rate after immediate nucleos(t) ide analogue (Nuc) therapy (30% vs. 47%) than that of the untreated patients with ALT > 10X upper ULN (Brahmania M et al CGH 2019). These controversial findings from 2 studies with small number of patients require larger studies to clarify.

Aims: We aimed to investigate the impact of Nuc therapy on HBeAg loss of chronic hepatitis B patients with hepatitis flare.

Methods: HBeAg positive CHB patients received Entecavir or Tenofovir monotherapy during 2006-2017 were recruited as treated cohort (Study group) while those without anti-viral treatment during 1980-2000 were enrolled as untreated cohort (Control group). Patients without proper monitor of ALT level, co-existence of other liver diseases and follow-up less than one year were excluded. Propensity score matching (PSM) was performed to adjust the difference between the Study and Control groups including age, gender, genotype, cirrhosis, ALT level and alfa-fetoprotein (AFP) level with 1:1 ratio.

Logistic regression was performed to investigate predictors for 1-year HBeAg loss.

Results: A total of 270 patients were analyzed with 135 patients in each arm after PSM. No differences of age, gender, genotype, cirrhosis, ALT level and AFP level were noted between two groups. The overall one-year HBeAg

2020 消化系聯合學術演講年會

P.011 loss rate was lower in the study than in the control group (31.9% vs. 48.2%, P = 0.006) especially when patients encountering hepatitis flare (ALT > 5X ULN) (Figure).

In multivariate analysis, ALT level > 10X ULN (<5X as referent, adjusted OR: 5.44, P<0.001) and Nuc treatment (untreated as referent, adjusted OR: 0.52 (0.31-0.88), P=0.015) were independent predictors for HBeAg loss by 1 year.

Conclusions: Nuc therapy resulted in lower HBeAg loss rate. Endogenous host immune driving toward HBeAg loss may be halted by Nuc therapy especially in those with hepatitis flare. The results add support to the recommendation of Asian-Pacific guidelines.

比較 B 型肝炎表面抗原陽性且罹患固體腫 瘤之病患於化學治療結束後再給予 24 週或 48 週抗病毒藥物預防之效果 THE EFFECT OF ANTIVIRAL PROPHYLAXIS FOR 24 WEEKS VERSUS 48 WEEKS AFTER COMPLETION OF CHEMOTHERAPY IN HBSAG-POSITIVE PATIENTS WITH SOLID TUMORS 1

1, 2

1, 2, 3

1, 2

1, 2, 3

魏銘漢 蘇東弘 劉俊人 曾岱宗 高嘉宏 1, 4 楊宏志 1 國立臺灣大學醫學院附設醫院內科部肝膽腸胃科 2 國立臺灣大學醫學院附設醫院肝炎研究中心 3 國立臺灣大學醫學院臨床醫學研究所 4 國立臺灣大學醫學院微生物學科暨研究所 Background: Hepatitis B virus (HBV) reactivation is a clinically important issue in HBsAg-positive cancer patients receiving cytotoxic chemotherapy. Prophylactic antiviral therapy is recommended by current guidelines, but the optimal duration after completion of chemotherapy remains uncertain.

Aims: This study aims to evaluate the optimal duration, the effectiveness, and safety of telbivudine in preventing HBV reactivation in HBsAg-positive patients with solid tumors receiving cytotoxic chemotherapy.

Methods: This is a prospective, open-label, randomized, single-center study. A total of 100 HBsAg-positive solidtumor patients who had detectable baseline HBV DNA and received cytotoxic chemotherapy were recruited.

Prophylactic telbivudine (600mg) daily was administered within one week prior to chemotherapy. Before 24 weeks after completion of chemotherapy, the eligible subjects were randomly assigned to either stopping telbivudine at 24 weeks or at 48 weeks after completion of chemotherapy at a 1:1 ratio. Biochemical liver function, HBV DNA and HBsAg levels were checked every three months until one year after stopping telbivudine. Among 100 eligible patients, 49 patients and 51 patients were assigned to the 24-week and 48-week groups, respectively. There were 8 patients dropped out in 24-week group and 11 patients in 48-week group. A total of 41 patients in the 24-week group and 40 patients in the 48-week group were included for analysis.

Results: In this study, all the patients achieved undetectable viremia, and no patients had virological breakthrough during the period of antiviral prophylaxis with telbivudine.

There were two patients, one in each group, experiencing

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P.012 HBV reactivation after discontinuing medication. The risks of hepatitis B flare after discontinuation of telbivudine was not significantly different between two groups, indicating that the antiviral prophylaxis until 24 weeks after completion of chemotherapy is sufficient in this clinical scenario. Further analysis disclosed estimated glomerular filtration rate eGFR had 8% increment at the end of trial in the 24 24-week prophylaxis group, and 18% increment in the 48-week group. There were 5 patients (12.2%) and 8 patients (20.5%) in the 24-week and 48-week groups, respectively, experiencing elevation of creatine kinase above the upper normal limit. However, no clinically significant rhabdomyolysis symptoms were observed in both groups.

Conclusions: In HBsAg carriers with solid tumors, patients receiving prophylactic telbivudine until 24 weeks after completion of therapy have similarly low risk of hepatitis B flare as compared to those with extension of prophylactic telbivudine to 48 weeks after completion of chemotherapy.

Nevertheless, careful monitor is warranted after stopping antiviral prophylaxis. Additionally, improvement of renal function was noted in both groups.

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檢測不到 B 型肝炎病毒的 C 型合併 B 型肝 炎病人使用直接抗病毒藥物治療後之 B 型 肝炎再活動化 HBV REACTIVATION IN HCV/HBV CO-INFECTION PATIENTS WITH UNDETECTABLE BASELINE HBV DNA AFTER DIRECT ANTIVIRAL AGENT THERAPY 林政寬 方惠玲 王思涵 施雅麗 李宗熙 亞東紀念醫院內科部肝膽胃腸科 Background: Reactivation of HBV infection during and after HCV/HBV co-infection with direct acting antiviral agent (DAA) was reported.

Aims: We aim to evaluate the HBV reactivation after DAA therapy without anti-HBV therapy for the HCV/HBV coinfection patients with undetectable baseline HBV DNA. Methods: A retrospective chart review was conducted on the subjects who underwent DAA therapy for HCV infection at Far Eastern Memorial Hospital from January 2017 to June 2019.

Results: A total of 40 cases diagnosed as HCV infection with positive HBsAg were treated with DAA. Twentytwo patients used antiHBV therapy, either preemptive use or using by reimbursement before DAA. Among 12 of 18 patients without receiving antiHBV therapy had undetected baseline HBV DNA. There were 5 men and 7 women with the age of 60±8.8 years (range: 47-80). The genotype of HCV was 1b (75%), 2 (8%) and 6 (17%). Seventeen percent of the patients had compensated liver cirrhosis. Medications were ledipasvir/sofosbuvir (50%), glecaprevir/pibrentasvir (42%) and elbasvir/grazoprevir (8%). All patient achieved sustained virologic response and ALT level were within normal limit at 12th weeks after therapy. Six patients (50%) had increasing HBV DNA at the end and 12th weeks after therapy (33%: increases of HBV DNA 1-2 log10 IU/ml and 33% had >2 log10 IU/ml). One cirrhotic patient had HBV reactivation with HBV DNA> 2 log10 IU/ml and ALT> 2 times of upper lower limit at 18th weeks after therapy and started entecavir therapy. There were no differences in the age, sex, BMI, medications, treatment duration, baseline ALT, HCV RNA, genotype, HBsAg (signal-to-cutoff ratio), Fib-4 score and cirrhotic patients between with and without increases of HBV DNA after DAA therapy.

Conclusions: The HCV/HBV co-infection patients with undetectable baseline HBV DNA had increases DNA after DAA without preemptive anti-HBV therapy. Although the majority was not associated with hepatitis, it still required be closely monitored especially in cirrhotic patients.

2020 消化系聯合學術演講年會

P.013 在 慢 性 B 型 肝 炎 病 人 使 用 TAF 或 是 TDF 治療對於肝癌發生的影響 IMPACT OF TREATMENT WITH TENOFOVIR ALAFENAMIDE (TAF) OR TENOFOVIR DISOPROXIL FUMARATE (TDF) ON HEPATOCELLULAR CARCINOMA (HCC) INCIDENCE IN PATIENTS WITH CHRONIC HEPATITIS B (CHB) 1

2

3

Wan-Long Chuang , Young-Suk Lim , Henry LY Chan , 4 5 6 7 Qin Ning , Jia-Horng Kao , Namiki Izumi , Scott Fung , 8 9 9 Dr Shalimar , John Flaherty , Shuyuan Mo , 9 10 11 Anuj Gaggar , Jinlin Hou , Wai Kay Seto Hepatobiliary Division, Department of Internal Medicine, 1 Kaohsiung Medical University Hospital Department of Gastroenterology, Liver Center, Asan 2 Medical Center, University of Ulsan College of Medicine Institute of Digestive Disease, Department of Medicine and Therapeutics, and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong 3 Kong Department of Infectious Diseases, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University 4 of Science and Technology Graduate Institute of Clinical Medicine, National Taiwan 5 University College of Medicine, Taipei, Taiwan Department of Gastroenterology and Hepatology, 6 Musashino Red Cross Hospital Toronto Centre for Liver Disease, Toronto General 7 Hospital, University Health Network Department of Gastroenterology, All India Institute of 8 Medical Sciences 9 Gilead Sciences Inc., Foster City, CA Department of Infectious Diseases, Nanfang Hospital, 10 Southern Medical University State Key Laboratory of Liver Research, The University of 11 Hong Kong Background: Potent antiviral treatment can reduce HCC incidence in patients with CHB. TDF and TAF are first-line treatments, and in Phase 3 studies through 3 years, TAF has shown antiviral efficacy similar to TDF, with higher rates of ALT normalization and no resistance.

A i m s : We e v a l u a t e d H C C i n c i d e n c e i n p a t i e n t s participating in these two ongoing studies.

Methods: HBeAg-positive (n=1039) and -negative (n=593) patients with HBV DNA ≥20,000 IU/mL and ALT >60

U/L (males) or >38 U/L (females) were recruited from 190 sites in 20 countries and randomized (2:1) to TAF 25 mg or TDF 300 mg given once daily for up to 3 years, followed by open-label TAF through Year 8. Patients with hepatic decompensation, co-infection with HCV/HDV/ HIV, or evidence of HCC at screening were excluded.

HCC was assessed by regular (every 6 months) hepatic ultrasonography introduced after Week 96 and throughout by local standards of care. Standardized incidence ratio (SIR) for HCC was calculated for observed cases relative to predicted risk using the REACH-B model.

Results: Through 4 years of follow-up, HCC occurred in 16/1632 patients (0.98%; TAF 7/1093 [0.64%]; TDF 9/539 [1.67%]). Of 16 cases of HCC, 5 and 11 were in cirrhotic and non cirrhotic patients respectively. Median (Q1, Q3) time to HCC onset was 566 (318, 855) days (TAF 747 [392, 1370], TDF 460 [180, 729] days). At baseline, relative to those without HCC, patients with HCC were older (median age 53 vs 40 y; p<0.001), had lower HBV DNA (6.3 vs 7.3 log IU/mL; p=0.041), and were more likely to be cirrhotic (FibroTest score ≥0.75; 31% vs 10%; p=0.004). With treatment (TAF or TDF), HCC incidence was significantly reduced (16 observed vs 35.3 predicted; SIR [95% CI] 0.45 [0.278 -0.740]) [Table]. For TAF-treated patients, a significant risk reduction was seen (7 observed vs 22.4 predicted, SIR [95% CI] 0.31 [0.149-0.655]), whereas with TDF there was a reduction in incidence but it did not achieve significance (9 observed vs 12.9 predicted, SIR [95% CI] 0.7 [0.364, 1.344]).

Conclusions: 1. In >1600 HBeAg-positive and -negative patients with CHB enrolled in 2 large Phase 3 studies, antiviral treatment for 5 years demonstrated: (1) Low rates of HCC with TAF or TDF treatment (1.0% and 1.9%, respectively); cumulative incidence (by KM) did not differ for TAF vs TDF. (2) Lack of ALT normalization at Week 24, advanced age, male gender, and cirrhosis were predictors of HCC development by MV analysis.

2. Significant reduction in HCC incidence vs predicted rates by REACH-B was seen for all cases and for patients with no cirrhosis at baseline In patients treated with TAF, a significant reduction in SIR was seen; for TDF there was a trend toward a significant reduction.

3. Additional follow-up and further assessment of HCC risk reduction using other risk estimators is needed to confirm these results.

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2020 消化系聯合學術演講年會

P.014 應用 B 型肝炎表面抗原定量與丙氨酸轉氨 酶動力學之概念可降低停藥後再次治療的 頻率但不會增加不良結果 APPLICATION OF THE CONCEPT OF HBSAG/ALT KINETICS DECREASE RETREATMENT RATE WITHOUT INCREASED ADVERSE OUTCOME 1,2

1,2

1,3

劉彥君 鄭文睿 廖運範 1 林口長庚紀念醫院肝膽腸胃科 2 長庚大學 3 林口長庚紀念醫院肝臟研究中心 Background: The concept of combination use of quantitative hepatitis B surface antigen (qHBsAg) and ALT kinetics during flare helps to identify “effective immune clearance” (effective flare) and “ineffective immune clearance” (ineffective flare) in patients encountering hepatitis flare off Nuc therapy. Decreasing qHBsAg prior to the peak of rising ALT during flares represents “effective immune clearance” against HBV. Conversely, rising qHBsAg during flares reflects “ineffective immune clearance”.

Aims: This study aims to compare the retreatment rate between with and without adopting the concept of HBsAg/ ALT kinetics during off-Nuc clinical relapse.

Methods: Hepatitis B e antigen (HBeAg)-negative patients, who had received entecavir or tenofovir and stopped therapy by APASL stopping rule with at least 6 months follow-up duration during January 2017 and June 2019 were recruited. Group A consisted all patients cared by 2 physicians who strictly followed APASL stopping rule /monitoring plan and re-treatment decision by HBsAg/ ALT kinetics prospectively during clinical relapse while the remaining patients were group B. Age, gender, HBV genotype, baseline alanine aminotransferase (ALT), qHBsAg, DNA, retreatment rate and adverse outcome were compared between two groups.

Results: Group A consisted of 93 patients and group B consisted of the remaining 330 patients. Group A patients were older (57 vs. 55 year-old; p =0.028), more frequently cirrhotic (51% vs. 24%; p <0.001), more treatment experienced(77% vs. 53%; p <0.001) and less frequent off-Nuc clinical relapse (42% vs. 55%; p =0.032), but comparable hepatitis flare (ALT > 5X ULN) rate (35% vs. 41%, P=0.319) and hepatic decompensation rate (1% vs. 1.5%, P=0.751) during median follow-up 1.9 years.

By adopting the concept of HBsAg/ALT kinetics to

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differentiate effective and ineffective immune clearance, only 22% of group A patients received retreatment, in contrast to 40% of group B (P=0.001).

Conclusions: The application of the concept of HBsAg/ ALT kinetics significantly reduces the retreatment rate in off-Nuc clinical relapse without increasing adverse outcome.

2020 消化系聯合學術演講年會

P.015 在病毒抑制之腎功能不全的慢性 B 肝病 人 從 TDF 或 其 他 口 服 抗 病 毒 藥 物 轉 換 至 TAF：第二期開放性臨床試驗 24 週的療效 與安全性 EFFICACY AND SAFETY OF SWITCHING TO TENOFOVIR ALAFENAMIDE IN VIRALLY SUPPRESSED CHRONIC HEPATITIS B PATIENTS WITH RENAL IMPAIRMENT: WEEK 24 RESULTS FROM A PHASE 2 OPEN-LABEL STUDY 1

2

3

Yi-Hsiang Huang , Wan Long Chuang , Young-Suk Lim , 4 5 6 Edward J. Gane , Claire Fournier , Sang Hoon Ahn , 7 8 9 Owen Tsang , Jeong Heo , Aric Josun Hui , 10 11 12 Magdy Elkhashab , Chi-Yi Chen , Wei-Wen Su , 13 13 13 John F Flaherty , Anuj Gaggar , Shuyuan Mo , 14 15 Syed-Mohammed Jafri , Giulo Marchesini , 16 Harry LA Janssen 1 Taipei Veterans General Hospital, Taipei City, Taiwan Hepatobiliary Division, Department of Internal Medicine, 2 Kaohsiung Medical University Hospital Department of Gastroenterology, Liver Center, Asan 3 Medical Center, University of Ulsan College of Medicine 4 Auckland Clinical Studies, Auckland, New Zealand Centre Hospitalier de l’Université de Montréal, Québec, 5 Canada 6 Yonsei Liver Center, Severance Hospital, Seoul 7 Princess Margaret Hospital, Hong Kong Research Institute of Medical Science, Pusan National 8 University Hospital, Busan, Republic of Korea 9 Alice Ho Miu Ling Nethersole Hospital, Hong Kong 10 Toronto Liver Centre, Toronto 11 Chia-Yi Christian Hospital, Chia-Yi City, Taiwan 12 Changhua Christian Hospital, Changhua City, Taiwan 13 Gilead Sciences Inc., Foster City, CA 14 Henry Ford Hospital, Detroit, MI 15 Università di Bologna, Italy Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, 16 Canada

on TDF with renal impairment who were switched to TAF were evaluated in this Phase 2 study.

Methods: CHB patients with renal impairment taking TDF for >=48 weeks and virally suppressed for >= 6 months with HBV DNA <20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG < 15 to <60mL/min) and 2) ESRD (eGFR CG < 15 mL/ min) patients on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks. Co-primary endpoints were proportion with HBV DNA <20 IU/mL and graded adverse events (AEs)/lab abnormalities at Week 24. Key secondary safety endpoints were changes in hip and spine bone mineral density (BMD) and serum markers of bone turnover, as well as changes in eGFRCG and urinary markers of tubular function (mod-severe renal impairment group only).

Results: 93 patients (Mod-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries. Median age was 65 years, 74% male, 77% Asian, 83% HBeAgnegative, up to 60% had low BMD at hip and/or spine, and 60% and 24% had a history of HTN and/or diabetes, respectively. Key efficacy/safety results at Week 24 are summarized in the Table. All patients on treatment at Week 24 maintained HBV DNA <20 IU/mL and a high proportion had normal ALT levels. Relative to baseline levels, switching to TAF from TDF resulted in increases in hip/spine BMD, decreases in bone turnover markers, as well as increases in eGFRCG and decreases in renal tubular markers. TAF was well tolerated with few having Grade 3 or 4 AEs (7.5%); no serious AEs related to study drug and no discontinuations due to AEs. Conclusions: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained and the bone and renal safety were improved 24 weeks after switching from TDF to TAF.

Background: TAF, a novel tenofovir prodrug, has demonstrated noninferior efficacy to TDF with superior bone and renal safety in virally suppressed CHB patients with eGFR (by Cockcroft-Gault; eGFRCG) >= 50 mL/min when switched from TDF. Aims: The efficacy and safety of virally suppressed patients

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2020 消化系聯合學術演講年會

P.016 慢性 B 及 C 肝炎雙重感染者接受直接作用 抗病毒藥物 (DAA) 治療引起 B 型肝炎發作 在真實世界經驗 REAL WORLD EXPERIENCE OF HBV REACTIVATION IN PATIENTS WITH DUAL CHRONIC HEPATITIS C AND B WHO RECEIVED DAA THERAPY 1

1,2

1,2,3,4

1

1,2

1,2

魏平雅 劉俊人 高嘉宏 楊宏志 曾岱宗 蘇東弘 1,2 1,2,3,4 劉振驊 陳培哲 1 臺灣大學醫學院附設醫院內科部肝膽腸胃科 2 臺灣大學醫學院附設醫院肝炎研究中心 3 臺灣大學醫學院臨床醫學研究所 4 臺灣大學醫學院附設醫院醫學研究部

Background: Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas. Treatment of chronic hepatitis C virus (HCV) infection using interferon-free direct-acting antivirals (DAAs) is associated with a high risk of HBV reactivation in patients with dual HCV and HBV infection. Current guidelines do not have consistent recommendations about the prevention of HBV reactivation.

Aims: This study aimed to review the real world data in terms of the rate and outcome HBV reactivation during and after DAA treatment in this special clinical setting.

Methods: A retrospective observational study was conducted at National Taiwan University Hospital (NTUH) to enroll patients aged above 18 with dual HBV and HCV infection who received DAAs from January 2017 to April 2019. Their baseline viral serology, HBV DNA, HCV genotype, HCV RNA, DAA regimens, use of nucleos(t)ide analogues(NA), alanine transaminase(ALT) levels, FIB4 index were reviewed from medical record if available.

HBV DNA levels were checked at the physician’s discretion. HBV reactivation was defined as 1) ≥ 2 log (100-fold) increase in HBV DNA compared to the baseline level, 2) HBV DNA ≥ 3 log (1,000) IU/mL in a patient with previously undetectable level, 3) HBV DNA ≥ 4 log (10,000) IU/mL if the baseline level not available, according to AASLD 2018 hepatitis B guidance. Hepatitis flare was defined as ALT ≥3 times baseline and >100 IU/ mL and HBV-associated hepatitis was defined as HBV reactivation with hepatitis flare.

Results: A total of 31 patients were enrolled (64.5% genotype 1, 32.3% genotype 2; 41.9% women; 61.3% baseline FIB-4 index >3.25). Most patients (71%) are treatment naïve to HCV. Nineteen patients(61.3%) had

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a detectable HBV DNA at baseline. Overall sustained virological response rates at 12 weeks (SVR 12) was 87.1% (96.4% after excluding the 3 patients). Eleven (35.5%) patients are not taking NA before DAA therapy.

Of the 11 patients not taking NA, five (45.5%) had HBV reactivation(3 before SVR 12 and 2 after SVR 12). Of the five patients, three (60%) had HBV-reactivation-associated hepatitis and all of them received NA treatment. One patient died of hepatic decompensation despite the initiation of NA therapy and the other two recovered without complications.

In patients taking NA before DAA therapy, none had HBV reactivation.

Conclusions: Our data consistently indicated that HBV reactivation rate was high (45%) in HCV and HBV dually infected patients not taking NA during and after HCV DAA therapy, and HBV reactivation-associated hepatitis rate was documented. Despite the growing awareness of HBV reactivation in such patients, mortality resulting from HBV-reactivation-associated hepatitis still occurs in our daily practice. Pre-emptive treatment for HBV should be considered in all HCV and HBV dually infected patients receiving HCV DAA therapy, especially in those with advanced liver disease.

2020 消化系聯合學術演講年會

P.017 使用惠立妥或貝樂克治療慢性 B 型肝炎代 償性肝硬化患者之發生肝癌之風險比較 COMPARING RISK OF HEPATOCELLULAR CARCINOMA DEVELOPMENT UNDER ENTECAVIR OR TENOFOVIR TREATMENT FOR PATIENT WITH CHRONIC HEPATITIS B-RELATED COMPENSATED LIVER CIRRHOSIS 1

2

1

1

1

were consistently supported by a subgroup analysis of patients initiating ETV or TDF treatment after the launch of TDF in 2011.

Conclusions: For treatment-naïve patients with CHBrelated compensated LC, after variable adjustments, PS approaches, and subgroup analyses, TDF treatment significantly lowered the risk of HCC development compared to the ETV treatment.

3

張國欽 邱月霞 林明宗 陳建宏 王景弘 簡榮南 1 胡琮輝 1 高雄長庚醫院胃腸肝膽科系 2 長庚科技大學高齡暨健康照護管理研究所 3 林口長庚醫院胃腸肝膽科系

Background: Long-term efficacy of comparing entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatments for prevention of disease progression to hepatocellular carcinoma (HCC) among high-risk patients with chronic hepatitis B (CHB)-related compensated liver cirrhosis (LC) is unknown.

Aims: To compare the longterm efficacyof ETV versus TDF regimens on HCC risk reduction for NA treatmentnaïve patients with CHB-related compensated LC and to evaluate predictive risk factors for HCC development.

Methods: From January 2008 to March 2018, retrospective study of 894 treatment-naïve patients with CHB-related compensated LC under ETV or TDF treatment were enrolled based on the longitudinal cohort study. Data were collected for up to 7.3-years of follow-up or after the launch of TDF in 2011. The cumulative incidence and risk factors of HCC development were assessed.

Results: Among the entire cohort, 678 and 216 patients received ETV and TDF treatments, respectively. The cumulative risk of HCC development at the 1, 3, and 5 years of follow-up was 1.6%, 11.3%, and 18.7%, respectively, in the ETV group; and 0.9%, 6.7%, and 10.7%, respectively, in the TDF group (p = 0.0076).

Univariate and adjusted-multivariable models revealed PLT count, DM comorbidity, FIB-4 index, and treatment with ETV vs. TDF as risk factors of HCC development.

TDF treatment resulted in lower risk of HCC development compared to ETV treatment with the adjusted hazard ratios (aHRs) of 0.59 (95% CI: 0.36-0.95), 0.59 (95% CI: 0.36-0.96), and 0.56 (95% CI: 0.31-0.98) under stepwise selection, propensity score (PS) adjustment, and PSmatching multivariable models, respectively. These findings

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2020 消化系聯合學術演講年會

P.018

P.019

全口服抗病毒藥物治療增進 HCV 合併 HIV 感染者的治療配合度及治療成效 INTERFERON-FREE THERAPY IMPROVE PATIENT ADHERENCE AND TREATMENT OUTCOME FOR HCV/HIV CO-INFECTED PATIENTS

慢性 C 肝病人接受口服抗病毒藥物後持續 病毒學反應的一致性與持續性 CONCORDANCE OF SVR12, SVR24 AND SVR DURABILITY IN CHRONIC HEPATITIS C PATIENTS RECEIVING DIRECTLY ACTING ANTIVIRALS

劉怡伶 顏旭亨 曾雅惠 黃秀萍 蘇培元 徐友春 彰化基督教醫院消化系中心

林詮斌 黃志富 黃釧峰 戴嘉言 余明隆 莊萬龍 1,2 1,2 葉明倫 黃駿逸 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學系

Background: In the last decade, the standard of care for HCV patients with pegylated interferon (PEG-IFN) alfa2a or alfa-2b plus ribavirin (RBV) is 24 to 48 weeks.

Patients usually could not tolerate or might have other contraindications to the treatment, especially in HCV-HIV co-infected population. With the introduction of interferonfree therapy, should be a concern to encourage these HCV/ HIV coinfection patients for HCV treatment.

Aims: This study aimed to evaluate HCV-HIV co-infected patients’ compliance during HCV treatment and SVR rate in a comparison between interferon-based and interferon-free DAAs regimens.

Methods: Total 54 HCV/HIV co-infected patients received Interferon based and Interferon-free based DAAs HCV treatments at Changhua Christian Hospital from November 2007 to June 2019. 22 patients received alfa-2a or alfa-2b (PEG-IFN) plus ribavirin. 27 and 5 patients had interferonfree DAAs with Harvoni and Maviret respectively. Clinical data and characteristics of these patients treated with pegylated interferon (PEG-IFN) alfa-2a or alfa-2b plus ribavirin and direct-acting antiviral agents (DAAs) were statistical analyzed.

Results: The development of new direct-acting antiviral agents (DAAs) provides hope in chronic hepatitis C and HIV co-infected patients. It has achieved sustained virological response (SVR) rates of up to 96% indirect-acting antiviral agents (DAAs), and 68% in pegylated interferon plus ribavirin (PEG-IFN/RBV) patients. The withdrawal rate in DAAs and PEG-IFN/RBV patients are 0% and 27% respectively. Both the SVR rate and withdrawal rate have shown a significant statistical difference in patients with genotype 1.

Conclusions: Improved therapeutic efficacy and tolerability are indicated in patients with DAAs. Patients had a significantly higher cure rate and better adherence to interferon-free DAAs regimen. So, direct-acting antiviral agents (DAAs) is a definite optimal treatment option for this population. It approaches better efficacy, improved tolerance and more safety profiles during the HCV treatment.

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1

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1,2

1,2

1,2

1,2

Background: Among chronic hepatitis C (CHC) patients treated with interferon-based therapy, sustained virological response (SVR) has been defined as undetectable HCV RNA throughout 24 weeks of post treatment follow-up period (SVR24). Due to high concordance of SVR24 and SVR12, defined as undetectable HCV RNA throughout 12 weeks of post treatment follow-up period in the era of directly acting antiviral agents (DAAs), SVR12 has been widely accepted as a valid efficacy endpoint. However, the concordance between SVR12 and SVR24 as well as SVR durability has rarely been systematically assessed in Taiwanese CHC patients.

Aims: The current study aimed to identify the timing of virological failure among CHC patients who achieved endof -treatment virological response (EOTVR) by DAAs. We also addressed the concordance of SVR12 and SVR24 and following SVR durability in patients who achieved SVR12.

Methods: We conducted a retrospective analysis among CHC patients who received all-oral DAA regimens between December 2013 and August 2019. HCV RNA was monitoring 4, 12, and 24 weeks, respectively, after the end of DAA treatment in patients with EOTVR. Among the patients whom achieved SVR24, the HCV RNA was followed annually for assessing SVR durability.

Results: Among 1077 patients with EOTVR, eleven (1.02%) patients experienced virological relapse. The most frequent timing of relapse was SVR4 (n=8), followed by SVR12 (n=2) and SVR 24 (n=1).

The positive predictive value (PPV) of SVR4 in predicting SVR12 was 99.8 %, whereas the PPV of SVR12 in predicting SVR24 was 99.8%, too . The patient who had detectable HCV RNA at SVR24 was with the same HCV genotype, HCV-1b, before and after DAA treatment.

Meanwhile, there was no any risk factor for re-infection for these patients. Further viral sequencing is ongoing to confirm the identity.

2020 消化系聯合學術演講年會

P.020 Among the patients whom achieved SVR24 (n=977), no patient had detectable HCV RNA after a median followup period of 1.25 years. The SVR durability after SVR24 is 100%.

Conclusions: SVR12 remains the standard endpoint for curative antivirals following DAA therapy. Although the incidence of late recurrence at SVR24 was rare, regular follow-up after DAAs treatment may be necessary for CHC patients in particular for patients with abnormal liver function.

Elbasvir (EBR) / Grazoprevir (GZR) 用於治 療 C 型肝炎病毒基因型第一型的病人是有 效且可耐受的：台灣多機構觀察性研究 ELBASVIR (EBR) / GRAZOPREVIR (GZR) IS EFFECTIVE AND TOLERABLE FOR THE TREATMENT OF HCV GT1INFECTED PATIENTS: A REAL WORLD MULTICENTER OBSERVATORY STUDY IN TAIWAN 1

1,2

詹益宗 劉俊人 1 臺大醫院內科 2 臺大醫院臨床醫學研究所 Background: Treatment of hepatitis C virus (HCV) by elbasvir/grazoprevir (EBR/GZR) was found to be efficacious and well tolerated in clinical trials.

Aims: This study aimed to evaluate the effectiveness and tolerability of EBR/GZR in the treatment of HCV genotype 1 (GT1)-infected Taiwanese patients.

Methods: Chronic hepatitis C (CHC) patients infected with GT1b or 1a without resistance-associated substitution, and treated with 12-week EBR/GZR were enrolled from 10 hospitals in Taiwan between August 2017 and December 2018. All clinical and virologic data were collected at each participating center. Primary efficacy endpoint was sustained virologic response at week 12 (SVR12) after end of the EBR/GZR therapy, assessed in the per-protocol population, which excluded patients with important deviations from the protocol. Analysis was also performed based on the modified full analysis set (FAS), which included all allocated patients receiving at least 4-week medication. Virologic failure was recorded as breakthrough, nonresponse, or relapse. Safety was assessed through collection of adverse events (AEs), physical examination, vital signs, and standard laboratory evaluations.

Results: Per protocol SVR12 rates were 99.5% (1169/1175) for all HCV genotype 1 patients. Among patients with stage 4 or 5 chronic kidney diseases, 100% (107/107) achieved SVR12. In univariate analyses, variables associated with SVR12 were treatment duration (P <0.0001) and treatment adherence (P <0.0001). 22.3% of the patients experienced adverse effects during treatment. Seven patients did not complete the treatment, five due to liver-unrelated deaths, one due to AE and one due to epilepsy. Conclusions: EBR/ GZR treatment was highly effective and well tolerated.

Conclusions: EBR/GZR treatment was highly effective and well tolerated.

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2020 消化系聯合學術演講年會

P.021 使 用 全 口 服 直 接 抗 病 毒 藥 物 治 療 HIV / HCV 合併感染患者有極佳的療效及良好的 耐受性 WELL TOLERABILITY AND HIGHLY EFFECTIVE TREATMENT RESPONSE FOR HUMAN IMMUNODEFICIENCY VIRUS-HEPATITIS C VIRUS COINFECTED PATIENTS TREATED

BY ALL ORAL DIRECT ACTING ANTIVIRALS 1

1,2

1

1,2

1,2

1,2

蘇品碩 蘇建維 吳思賢 朱啟仁 李發耀 黃怡翔 1,2 侯明志 1 臺北榮民總醫院肝膽胃腸科 2 國立陽明大學醫學院醫學系

Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is common duo to sharing the same route of transmission. Literatures suggested patients with HIV-HCV coinfection are associated with accelerated rates of hepatic fibrosis, increased the frequency of hepatic decompensation, and the development of hepatocellular carcinoma. Historically, sustained virological response (SVR) rates for these patients treated by pegylated interferon (IFN)-based therapy are generally poor due to advanced liver disease, immune dysfunction and poor medical adherence.

Aims: This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for HIVHCV coinfection patients.

Methods: Between January 2017 to June 2019, 50 consecutive HIV-HCV coinfection patients who treated with all oral DAAs (paritaprevir/ritonavir, ombitasvir and dasabuvir: 7, daclatasvir and asunaprevir: 1, glecaprevir and pibrentasvir: 15, sofosbuvir-based: 27) by investigators were enrolled for analyses. Selection of DAAs regimen was based on genotype/subtypes, patient characteristics, potential drug to drug interaction profiles and criteria of Health-Insurance reimbursement. SVR12 was defined by undetectable HCV RNA (< 15 IU/mL) at treatment end and 12 weeks after the completion of therapy.

Results: Mean age of enrolled patients was 42.1 +-10.3 years, 92% of them was male and 20% have cirrhosis.

Nine (18%) of them failed to previous IFN. Genotype distribution was as follows: 1a: 7, 1b: 22, 2: 14, 3: 1, and 6: 6. Baseline HCV RNA level before DAAs was 6.53+0.9 log10IU/mL. After DAAs treatment, 19 patients have checked week 4 HCV RNA level and the distribution of

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was as follows: undetectable (< 15 IU/mL): 17 (89.5%) and 15 to 50 IU/mL: 2 (10.5%), respectively. The rates of undetectable HCV RNA at the end of therapy were 100%.

Subjective and laboratory adverse events during therapy were generally mild and no patients early terminated therapy. After post-treatment follow up, all 50 patients (100%) achieved SVR12.

Conclusions: For HIV and HCV coinfection patients, which identified as a difficult-to-treat population by IFNbased therapy in the past with unmet medical needs, highly effective treatment response and well tolerability were achieved by all oral DAAs.

2020 消化系聯合學術演講年會

P.022

P.023

慢性 C 型肝炎以全口服抗病毒藥物治療後 肝臟纖維化的非侵襲性評估 NONINVASIVE FIBROSIS EXAMINATION (FIBROSCAN) AMONG CHRONIC HEPATITIS C PATIENTS RECEIVING DIRECT ANTIVIRAL THERAPY

台灣屏東縣南部地區慢性 C 型肝炎患者接 受直接作用抗病毒治療的真實經驗 REAL-WORLD EXPERIENCE OF DIRECT-ACTING ANTIVIRAL REGIMEN IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION IN SOUTHERN PINGTUNG

1,2

1

1

1

1

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林宜竑 戴嘉言 黃志富 余明隆 莊萬龍 1 高雄市立小港醫院 2 高雄醫學大學附設中和醫院

沈昌平 李昶毅 許綜麟 石志安 1 安泰醫療社團法人安泰醫院胃腸肝膽科 2 安泰醫療社團法人安泰醫院藥劑部

Background: Chronic hepatitis C (CHC) is the leading cause of hepatocellular carcinoma (HCC) globally.

Nowadays, direct anti-viral agent (DAA) was powerful treatment for virus elimination. Therefore, estimation of liver fibrosis severity is important for patient prognosis, treatment efficacy, HCC surveillance and determining the best treatment strategies in HCV patients. Liver biopsy, as the gold standard method for the assessment of liver fibrosis, is an invasive method associated with patient discomfort and sometimes with serious complications.

Several ultrasound-based methods have been developed and validated for assessing the degree of fibrosis and cirrhosis by measuring liver stiffness in the past decade.

Aims: The aims of this project are to observe short-term change of fibrotic change of by Fibroscan for CHC patients who received anti-viral treatment (Direct anti-viral agent, DAA), to evaluate to the influence of the medication.

Methods: Total 400 patients with HCV post direct antiviral agent (DAA) treatment were involved in this study.

They received DAA treatment and performed non-invasion examination (Fibroscan) after 6 months and 12 months.

Results: There were 73% decrease and 27% increase in liver fibrosis after 6 months of treatment. There were 62% decrease and 38% increase in liver fibrosis after 12 months of treatment. After 6 months of treatment, 31% patients had decrease fibrotic stage, 6 % patients had increase fibrotic stage and 63% patients had stable fibrotic stage. After 12 months of treatment, 38% patients had decrease fibrotic stage, 15 % patients had increase fibrotic stage and 47% patients had stable fibrotic stage.

Conclusions: After DAA treatment, some patients would improve their fibrotic change. However, still some patient would progress fibrotic change. More patient numbers and long-term following were needed for further study.

Background: It is well known that direct-acting antiviral agents(DAA) has high sustained virologic response(SVR) and less side effect in HCV treatment experience. Ministry of Health and Welfare relax HCV DAA treatment criteria in National Health Insurance since 2019 and wish to eliminate Taiwan HCV infection in 2025. As one health provider in southern Pingtung, we would like to share our HCV treatment experience.

Aims: Our objective is to collect and analysis HCV treatment data in southern Pingtung Methods: We collected HCV DAA treatment data from 2018 January to 2019 July retrospectively in Antai hospital.

Patient who undergo DAA treatment program was enrolled in this study. To identify Child-Pugh score, patient’s biochemistry data before DAA treatment was analyzed.

To address other comorbidity, we traced patient’s previous medical record in our hospital.

Results: There were total 276 patients(male:126; female:150) undergo DAA treatment program in our hospital since 2018. Most of them were treatmentnaïve(n=256, 92.75%), and there were 111 elder people. (age>65, 40.22%) There were 46 cirrhosis patient; Child-Pugh class A and class B were 43(15.58%) and 3(1.09%) people respectively. To genotype analysis, type 2 was the first place(n=122, 44.2%) and type 1b was the second.(n=106, 38.41%) Harvoni(n=91, 32.97%) and Zepatier(n=80, 28.99%) regimen treated more than half of these patients. 265 patients completed treatment course and most of them(n=263, 99.25%) did not detect HCV RNA level at the end of treatment(EOT); 259 patients follow up at after 12 weeks later after treatment course completed; 253 patients achieved SVR12(97.68%). 8 patients(2.9%) did not finish treatment course due to interruption.

131 patients(47.46%) was found with higher S-GPT level than baseline before DAA treatment. We were also aware of that Alpha fetoprotein(AFP) level drop after treatment

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P.024 course completed.

Conclusions: Even in southern Pingtung, the result of curing HCV infection with DAA treatment was very encouraging. High EOT and SVR12 rate were found just like other real world treatment experience. Only few people would quit treatment because of side effect. We would keep making effort to eliminate HCV infection in southern Pingtung. But it was quite challenging to find out unawareness HCV patient.

SOF/VEL 於 6 歲至未滿 18 歲之慢性 C 型 肝炎未成年患者之安全性及療效研究 THE SAFETY AND EFFICACY OF SOFOSBUVIR/VELPATASVIR IN PEDIATRIC PATIENTS 6 TO < 18 YEARS OLD WITH CHRONIC HEPATITIS C INFECTION 1

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Maureen M. Jonas , Rene Romero , Etienne M. Sokal , 4 5 6 Philip Rosenthal , Gabriella Verucchi , Chuan-Hao Lin , 7 8 9 Jessica Wen , Michael R Narkewicz , Sanjay Bansal , 10 10 10 Jiang Shao , Sean Hsueh , Anuj Gaggar , 10 11 Kathryn Kersey , Regino P. Gonzalez-Peralta , 12 13 Daniel H. Leung , William F. Balistreri , 14 15 Karen F. Murray , Kathleen B. Schwarz 1 Boston Children’s Hospital, Boston, MA, USA Emory University School of Medicine and Children’s 2 Healthcare of Atlanta, Atlanta, GA, USA Cliniques Universitaires Saint-Luc, UC Louvain, Brussels, 3 Belgium University of California San Francisco, San Francisco, CA, 4 USA 5 University of Bologna, Bologna, Italy 6 Children’s Hospital Los Angeles, Los Angeles, CA, USA University of Pennsylvania and The Children’s Hospital of 7 Philadelphia, Pennsylvania, USA University of Colorado School of Medicine and Children’s 8 Hospital of Colorado, Aurora, USA 9 Kings College Hospital, London, United Kingdom 10 Gilead Sciences, Inc, Foster City, CA, USA Pediatric Gastroenterology, Hepatology and Liver Transplant, AdventHealth for Children, Orlando, FL, 11 USA Baylor College of Medicine and Texas Children’s Hospital, 12 Houston, TX, USA Cincinnati Children’s Hospital Medical Center, Cincinnati, 13 OH, USA University of Washington School of Medicine and Seattle 14 Children’s Hospital, Seattle, WA, USA Johns Hopkins University School of Medicine, Baltimore, 15 United States, Boston, MA, USA Background: Direct acting antiviral (DAA) regimens have been approved for the treatment of HCV in adolescents aged 12 to <18 years, but for younger children, the standard of care is still pegylated‐interferon plus ribavirin for up to 48 weeks. The current study evaluated the safety and efficacy of an all‐oral DAA treatment with the pangenotypic

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P.025 regimen of sofosbuvir (SOF)/velpatasvir (VEL) in children 6 to <18 years old.

Aims: To evaluate the safety and efficacy of an all‐ oral DAA treatment with the pangenotypic regimen of sofosbuvir (SOF)/velpatasvir (VEL) in children 6 to <18 years old.

Methods: Patients aged 6 to <18 years old with chronic HCV of any genotype were enrolled into this open‐label, ongoing study to receive the fixed dose combination SOF/ VEL. Patients 6 to <12 years old received SOF/VEL 200 mg/50 mg and 12 to <18 years old received SOF/VEL 400mg/100mg once daily for 12 weeks. The key efficacy endpoint was SVR12. Safety was assessed by adverse events (AEs) and clinical/laboratory data. Intensive pharmacokinetic (PK) sampling on Day 7 in a subgroup of patients (N=17) of each age group was done to confirm the appropriateness of the chosen dose.

Results: A total of 102 patients 12 to <18 years old and 73 patients 6 to <12 years were enrolled and treated. The genotype distribution overall was 75% GT1, 5% GT2, 13% GT3, 3% GT4, 3% GT6; 51% were female, 80% white, 85% treatment naïve, and 91% vertically infected. Intensive PK confirmed that the doses selected were appropriate. The SVR12 rate among patients 12 to <18 years old was 95% (97 of 102) and among the 6 to <12 years old was 92% (67 of 73); one patient in each age group had virologic failure and the remaining 9 patients did not achieve SVR for nonvirologic reasons such as lost to follow-up. Most AEs were mild or moderate in severity. In total, 5 subjects had a serious AE, none of which was attributed to treatment. Two patients discontinued treatment due to AEs; neither AE was considered treatment related. The most common AEs (>15% of patients) were headache, fatigue, and nausea in adolescents and vomiting, cough and headache in 6 to <12 year olds.

Conclusions: In patients 6 to <18 years old with chronic GT1, 2, 3, 4 or 6 HCV infection, treatment with SOF/ VEL for 12 weeks resulted in ≥92% SVR12 rate. This pangenotypic regimen was well tolerated overall, supporting its potential as a treatment option for children 6 to 17 years of age. The study is ongoing in children aged 3 to <6 years old.

洗腎與非洗腎 C 肝患者在接受直接抗病毒 藥物治療後有不同的 FIB-4 scores 表現 DIFFERENT PRESENTATION OF FIBROSIS-4 SCORES IN DIALYSIS AND NON-DIALYSIS PATIENTS WITH HEPATITIS C RECEIVED DIRECTACTING ANTIVIRAL THERAPY 蘇培元 顏旭亨 徐友春 許伯格 蘇維文 彰化基督教醫院胃腸肝膽科 Background: Previous data had showed the fibrosis markers were declined in patients who had hepatitis C virus (HCV) infection and successfully treatment with direct-acting agents (DAA). Little is known about that if the effect is the same in dialysis patients with HCV receiving DAA therapy.

Aims: We try to analyze the serial dynamic change of liver enzymes, platelet and fibrosis-4 scores (FIB-4) in dialysis and non-dialysis patients with HCV who achieved SVR after DAA therapy.

Methods: Dialysis patients had chronic HCV infection and achieved SVR to DAA therapy between January 2017 and Jun 2019 were enrolled and non-dialysis patients with HCV infection and achieved SVR to DAA therapy (Glecaprevir/ Pibrentasvir) between January 2019 and Jun 2019 were enrolled as control group retrospectively.

Results: The dialysis group enrolled 50 patients included 45 patients received hemodialysis and 5 patients received CAPD. The non-dialysis control group collected 77 patients.

All patients had SVR after DAA therapy. The FIB-4 at baseline were similar between the two groups (p= 0.068) while the GOT and GPT were lower in dialysis group and platelet was higher in non-dialysis group. The FIB-4 scores of dialysis group at baseline, RVR, end of treatment (EOT) and SVR were 2.87 (1.64-4.23), 2.57 (1.46-3.39), 2.66 (1.733.31) and 2.69(1.52-3.41) respectively ( P = 0.047, baseline vs RVR; p = 0.211, baseline vs EOT; p = 0.306, baseline vs SVR). The FIB-4 scores of non-dialysis group at baseline, RVR, end of treatment (EOT) and SVR were 2.31 (1.312.56), 2.09 (1.45-2.46), 1.99 (1.28-2.41) and 1.92(1.182.29) respectively ( P = 0.103, baseline vs RVR; p = 0.027, baseline vs EOT; p = 0.07, baseline vs SVR).

Conclusions: The improvement of FIB-4 scores was observed in non-dialysis patients with HCV achieved SVR after DAA therapy but not in dialysis patients. It may be explained by the lower GOT and GPT level at baseline that lead to the change of GOT and GPT over treatment was smaller in dialysis patients. Further large-scale studies are needed to confirm the finding.

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P.026 院內病人 C 型肝炎篩檢 -- 一個快速有效且 低成本的方式找出醫院潛在的 C 肝病人 IN HOSPITAL SCREENING OF HCV PATIENTS—AN EFFECTIVE AND LOW COST METHOD FOR IDENTIFYING HCV PATIENTS IN HOSPITAL 1

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牟聯瑞 王淑貞 李崇瑋 1 臺南市立醫院內科胃腸肝膽科 2 臺南市立醫院檢驗科 3 臺南市立醫院內科胃腸肝膽科 Background: In Oct. 2018, the minister of Taiwan health and welfare declared to eliminate HCV by 2025. This mission statement is 5 years ahead of WHO’s commitment.

The ministry of health and welfare also published “Taiwan Hepatitis C Policy Guideline” as the guideline of treatment, screen and prevention of HCV. In this guideline, about 250,000 hepatitis C patients will be treated by DAAs. However, the screening of HCV covering rate is less than 30% in most cities and counties in Taiwan. In such a circumstances, how to screen and find the HCV patients become a most important issue for eliminate HCV by 2025.

Aims: To find the potential HCV patients who visit to our outpatient clinic (OPD) by a most cost-effective way.

Methods: We setup a computer program and add on to the hospital information system (HIS). If a patient had an blood drawing order from his/her physician during one OPD visit (no matter what items of blood test, for example AC sugar etc.), the computer will search the data bank of our hospital to find if the patient received the anti-HCV examination or not. If the computer didn’t find the anti-HCV data, it will add on the examination of anti-HCV item automatically.

The response time of searching anti-HCV result and add on the item of blood test is very rapid without of any delay.

This kind of screening can be done in daily practice of OPD without any complaints from physicians and patients.

If the anti-HCV data showed positive, patient will be referred to GI specialist in the next visit for further HCV profiles examination, mainly HCV viral load and genotype.

The case manager of hepatitis will examine the data every month, if the patients didn’t have further examination, they will be call back for such blood tests.

Results: From July, 2019 to Dec. 2019, a total of 24,237 OPD patients received this “in hospital HCV screening program”. Anti-HCV positive were found in 1,008 patients (4.2%). Up to mid-December 2019, a total of 477 antiHCV+ patients had received HCV RNA examination.

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Among them, 194 (40.7%) patients had positive HCV RNA. However, after exclusion of those patients who received interferon based or oral DAAs treatment with SVR (no anti-HCV data in our HIS), 336 patients belonged to the no treatment group. In such circumstances, the detection rate of newly found patients became 57.7% (194/336). Further screening of patients is still on going and more HCV patients will expect to be identified in the future. The direct cost of each anti-HCV test is about 40 NTD and each HCV viral load test costs about 1200 NTD. After re-adjust the anti-HCV positive and HCV viremia rate in our study, it will cost about 5,500 NTD to find a HCV patient in our hospital. If we exclude the HCV RNA test in those patients who had received previous HCV treatment with SVR (mainly Peginterferon+Ribavirin), the cost will further down to 3900 NTD. The total cost to find a newly diagnosed HCV patient is directly related to HCV prevalence rate in that area. We also found the anti-HCV titer is also a positive predictive factor for HCV viremia.

Further reduction of cost can be made if we apply this data in the future.

Conclusions: The treatment efficacy of new all oral DAAs for HCV is undoubtedly high (>98%). How to screen the HCV patients become a most important issue and challenge for the government’s policy “elimination of HCV by 2025”.

According to Taiwan Hepatitis C Policy Guideline, there are many ways to screen the HCV patients such as mass screening from high risk society, anti-HCV examination in both public and private health examination or find the antiHCV + patients from blood donor bank. However, all these methods are either high cost or a time consuming works.

Many patients didn’t know their HCV status, even though they are regularly followed up at hospital due to other diseases. By using this “in hospital screen” model, we can screen a large number of patients and find a HCV patient with a relatively low cost in a very short period of time especially in those high anti-HCV prevalence areas.

2020 消化系聯合學術演講年會

P.027

P.028

C 型肝炎病毒抗體血清檢驗值可做微慢行 C 型肝炎活動性工具 HIGH EFFECTIVE SCREENING CHRONIC HEPATITIS C BY TITER OF ANTI-HCV

使用全口服直接抗病毒藥物治療各種不同 基因型之慢性 C 型肝炎合併腎衰竭血液透 析患者有極佳的療效及良好的耐受性 UNIVERSALLY HIGH RATES OF TREATMENT SUCCESS AND EXCELLENT SAFETY PROFILES

BY ALL ORAL DIRECT ACTING ANTIVIRALS FOR DIFFERENT GENOTYPES OF CHRONIC HEPATITIS C WITH END-STAGE RENAL DISEASE UNDER REGULARLY HEMODIALYSIS

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侯佳儀 陳志州 董宏達 李佩倫 莊棠惟 1 柳營奇美醫院臨床病理科 2 柳營奇美醫院胃腸肝膽科

Background: Screening chronic hepatitis C for therapy is the first step to eradication viral hepatitis C infection. A costeffective method for mass screening will be a major factor to eradicate this disease. The level of anti-HCV had been report to correlate with activity of chronic hepatitis C and serum hepatitis C virus core antigen (HCVcAg) had reported to correlate with HCV RNA above 3000 IU/mL. However, the cost of HCVcAg is higher than anti-HCV. These study is to test the sensitivity and specificity of anti-HCV. Aims: Study the level of anti-HCV for screening the activity of HCV and the role of HCVcAg as a supplement when the level of anti-HCV is low.

Methods: Five hundreds and seventy-one patients positive for test of anti-HCV within 1 June 2019 to 30 Nov 2019, excluding 122 no data of HCV RNA and 53 had eradicated virus by therapy, totally 396 patients were enrolled for this study. Anti-HCV and HCVcAg were tested with Abbott Archetect®; HCV RNA were tested by Abbott Real Time HCV assay.

Results: Within 396 patients 72.5% (287/396) showed positive of HCV RNA. In 57 patients who had anti-HCV level at 0.1-5 IU/mL, the HCV RNA positive rate is 3.5% (2/57). In 37 patients who had anti-HCV level at 5.1-10 IU/mL, the HCV RNA positive rate is 7.8% (5/37). In 214 patients who had anti-HCV level at 5.1-10 IU/mL, the HCV RNA positive rate is 91.6% (196/214). In 84 patients who had anti-HCV level at 10.1-25 IU/mL, the HCV RNA positive rate is 95.2% (80/84). For the low positive rate of HCV RNA in patients with anti-HCV level between 5.110 IU/ml, we supplement used HCVcAg instead of HCV RNA in 39 patients and found sensitivity is 100% with 93% specificity (two false negative, HCV RNA: 11446 IU/mL and 1083 IU/mL. Conclusions: High positive rate of HCV RNA when antiHCV tilter is higher than 10 IU/Ml. HCVcAg is closely related to HCV RNA. Mass screening with anti-HCV level with supplement HCVcAg during anti-HCV level at 5.1-10 IU/mL is a method with high efficient and low cost.

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朱啟仁 魏天心 蘇品碩 吳思賢 黃怡翔 侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學糸內科

Background: The prevalence of hepatitis C virus (HCV) virus infection in patients with end-stage renal disease (ESRD) under hemodialysis is considerably higher than general population. HCV-infected ESRD patients has been associated with a higher morbidity and mortality because of the hepatic and extrahepatic manifestations of disease.

During the era of interferon (IFN)-based therapy, lower percentage of HCV-infected ESRD patients had been offered antiviral therapy due to low cure rates and higher incidence of adverse events. In recent years, the therapeutic landscape of chronic hepatitis C (CHC) changed rapidly after the invention of all oral direct acting antivirals (DAAs).

Aims: This study was aimed to investigate the efficacy and safety of all oral DAAs for HCV-infected ESRD patients under regular hemodialysis.

Methods: Between January 2017 to June 2019, a total of 62 HCV-infected ESRD patients under hemodialysis who treated with all oral DAAs (paritaprevir/ritonavir, ombitasvir and dasabuvir: 12, daclatasvir and asunaprevir: 16, elbasvir and grazoprevir: 5, glecaprevir and pibrentasvir: 29) by investigators were enrolled for analyses. Selection of DAAs regimen was based on genotype/subtypes, patient characteristics, potential drug to drug interaction profiles and criteria of Health-Insurance reimbursement. SVR12 was defined by undetectable HCV RNA (< 15 IU/mL) at treatment end and 12 weeks after the completion of therapy.

Results: Mean age of enrolled patients was 62.8±10.7 years, 56.5% of them was male and 29.0% have cirrhosis.

Fifteen (24.2%) of them failed to previous IFN. Genotype distribution was as follows: 1a: 2, 1b: 41, 2: 18, and 6: 1.

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P.029 Baseline HCV RNA level before DAAs was 5.53±1.28 log10 IU/mL. After DAAs treatment, 37 patients have checked week 2 HCV RNA level and the distribution of was as follows: undetectable (< 15 IU/mL): 29 (78.4%), 15 to 50 IU/mL: 2 (5.4%), 50 to 100 IU/mL: 2 (5.4%), and > 100 IU/mL: 4 (10.8%), respectively. The rates of undetectable HCV RNA at week 4 and the end of therapy were 93.8% and 100%, respectively. Subjective and laboratory adverse events during therapy were generally mild and no patients early terminated therapy. After posttreatment follow up, all 62 patients (100%) achieved SVR12.

Conclusions: Among different genotypes of CHC with ESRD under regular hemodialysis, regardless of previous antiviral therapy or not, excellent safety profiles and universally high rates of SVR were achieved by all oral DAAs.

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夏奉寧治療 C 肝 2 型的現實世界療效 - 台 灣單一中心經驗 .

REAL-WORLD EFFECTIVENESS OF LEDIPASVIR-SOFOSBUVIR FOR PATIENTS WITH HEPATITIS C GENOTYPE 2 INFECTION IN TAIWAN 1,3

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陳志城 曾政豪 曾兆明 彭道雄 陳子皓 羅錦河 2,3 2,3 1 2 2,3 2,3 許家彰 林志文 陳啓仁 徐銘宏 王文 戴啟明 1 義大癌治療醫院胃腸肝膽科 2 義大醫院胃腸肝膽科 3 義守大學

Background: Hepatitis C remains a major disease burden in Taiwan with an estimated prevalence of viremia in 400,000 populations at the end of 2018.

SOF/LED combination was the only approved drug for genotype 2 patients during Jan 2019~May 2019 in Taiwan after the integrated analysis from New Zealand, Japan, and Taiwan all showed high response rate around 98%. Due to lack of such recommendations in three major hepatology societies, we need more real-world evidence to support this policy recommendations.

Aims: In this prospective observational study, we tried to analyze the effectiveness of SOF/LED combination in a real-world setting.

Methods: From Jan 2019 to July 2019, a total of 212 subject with genotype 2 hepatitis C were enrolled. Patient characteristics were collected regarding their age, gender, interferon exposure history, concomitant hepatitis B or human immunodeficiency virus infection, history of hepatocellular carcinoma, HCV viral load, genotype, and treatment regimens. The primary endpoint was the proportion of patients with an SVR12.

Data regarding continuous variables are presented as the mean ± SD, and categorical variables are given as percentages. Factors associated with SVR12 were analyzed in subgroup analysis by using Student's t test, chi-square test, or Fisher's exact test, as appropriate.

Results: The study flowchart was summarized in Figure 1.

Two hundred and twelve patients (84.8%) received SOF/ LDV with or without ribavirin. 207 out of 212 (97.6%) patients received SOF/LDV had complete treatment.

The mean age (±SD) was 61(± 11.5) years, and 93 (44.0%) were men and 119 (56.0%) were women. Eighteen (8.5%) patients have compensated cirrhosis and fourteen (6.6%) patients had failed previous interferon treatment.

Concomitant HBV or HIV infections were found in

2020 消化系聯合學術演講年會

P.030 10(4.7%) and 5(2.4%) patients, respectively (table 1) Ten out of 212 patients failed to reach SVR12 and SVR12 rate was 95.3%. Three patients had premature discontinuation of treatment because of drug related adverse events, including severe headache in 2 patients and allergic skin rash in one patient (Figure 1). Therefore, the discontinuation rates of due to adverse events were1.4%.

Conclusions: Real world data supported that SOF/LDV for the treatment of genotype 2 chronic HCV was safe and well tolerated. Two patients died of non-DAA related death.

單一醫學中心：C 型肝炎病患召回治療經驗 EFFICACY OF A CALL BACK METHODOLOGY IN HCV ELIMINATION WITH DAA THERAPY: A SINGLE CENTER EXPERIENCE 1,2

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簡佐軒 陳立偉 張家昌 劉競榮 嚴卓立 李宗實 1,2 1,2 錢政弘 胡瀞之 1 基隆長庚醫院胃腸肝膽科 2 基隆長庚醫院社區醫學研究中心

Background: Hepatitis C virus (HCV) has cause about 1.46 million deaths in the world wind in 2013 . It even higher than that from HIV. WHO has setting a goal to treat 80% of HCV by 2030. In Taiwan, in 1996-2005, prevalence of anti-HCV positive was 4.4% and 2.3% in Keelung City. (Chen CH, et al. Journal of the Formosan Medical Association 2007) Aims: This study as a experience of first-step call-back experience of HCV treatment with DAA therapy .

Methods: A single center study. We establish a call back methodology for elimination. The patient who has been found to have anti-HCV positive was enroll form resource below: (group 1) form the data base of Keelung Chang Gung hospital form 1999 to 2019 , (group 2) community health check form Anle Dist., Gongliao Dist., Ruifang Dist. and Wanli Dist. Patient are call back by hospital hepatitis case manager. (group 3) Patient who was under regular hemodialysis at our hospital and has anti-HCV positive are refered by nephrologists to our out patient clinic.

Patient who has HCV RNA positive was treated with DAA therapy according to 2018 EASL Guideline.

Results: Patient number of who was call back form data base of our hospital was 6769. There are 1157 patient who have been regular follow up at our hospital and 955 patient was expire. The HCV RNA positive in patient with AntiHCV positive was 30.1%, 63.7%, 75% in goup 1, goup2, group 3. The prevalence of HCV in Anle Dist. was 2.5% and it was 12.6% in patient under regular hemodialysis in our hospital.

Conclusions: In our study the prevalence of HCV infection in 2.5%. It was similar compare with previous study in Keelung (2.3%). The prevalence of HCV infection in patient under regular hemodialysis was relative higher compare with other goups in this study. The result was similar to the result of previous study (13.2% in CKD stage 4 and 5). The HCV RNA positive in patient with Anti-HCV positive was lower in patient form our hospital data may due to previous interferon therapy. It was 63.7% in newly diagnosed HCV in new diagnosis group. It may reflect the chronic HCV prevalence in Keelung area.

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P.031 在 DAA 年代慢性 C 型肝炎治療：醫學中心 與地區醫院之比較 CHRONIC HEPATITIS C TREATMENT IN THE DAAS ERA: REFERRAL CENTER VS DISTRICT HOSPITAL 1, 2

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陳洋源 顏旭亨 吳順生 蘇培元 楊佳偉 黃詠峰 1 彰化基督教醫院 2 員林基督教醫院

2

Background: Chronic hepatitis C (HCV) is the main cause of progressive liver diseases. Almost of people infected with HCV develop chronic hepatitis, of which 20%-40% will develop liver cirrhosis or hepatocellular carcinoma (HCC) 20-30 years after infection. The previous treatment was not very effectively and severe adverse events. The introduction of oral direct-acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment.

Aims: This study investigates the efficacy of DAAs treatment between referral center and district hospital after massive treatment agreement of national health insurance administration ministry of health and welfare. The study also investigates the liver cirrhosis and HCC incidences between two hospitals.

Methods: This study retrospectively compares the efficacy of DAAs treatment for chronic hepatitis C and HCC incidence before treatment between Changhua Christian hospital (CCH) which is tertiary referral center and YuanLin Christian Hospital (YLCH) which is district hospital from 2018, January to 2019, October. There are totally 1055 cases of chronic hepatitis C which received DAAs treatment in CCH. These 1055 patients, including 49.9% men and 50.1% women, constituted our study population.

There are totally 663 cases of chronic hepatitis C which received DAAs treatment in YLCH. These 663 patients, including 45.1% men and 54.9% women, constituted our study population.

Results: There are no significant difference in age, gender, BMI, viral road, genotype in both groups. The referral center has more severe liver impairments, including pre-treatment Alanine aminotransferase, albumin, total bilirubin, and cirrhosis than district hospital (P= 0.035, <0.001, <0.001, and <0.001). The sustained virologic response of DDAs treatment for chronic hepatitis C is no significant different in both group in spite of liver cirrhosis or not. The HCC before DAAs treatment was detected 30 cases (2.8%) in referral center and 40 cases (6%) in district hospital. The incidence of HCC detection is less in referral

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center than district hospital (p= 0.001). There are no severe adverse events in both group except one case which develop tactile hallucination during treatment. The survival of DAAs treatment for chronic hepatitis C and short term of HCC treatment are no significant different in two group.

Conclusions: 1. There is no significant different achievement of SVR of chronic hepatitis C in two hospitals.

2. The HCV related liver cirrhosis has more incidence in referral center than district hospital. 3. The HCC incidence before HCV treatment is significant increase in district hospital. 4. The prognosis of chronic hepatitis C and short term of HCC treatment are no significant different in two hospitals.

2020 消化系聯合學術演講年會

P.032 C 型肝炎口服抗病毒藥物治療 HIV/HCV 共 同感染的效果和安全性分析：中部二家醫學 中心的臨床經驗 THE EFFICACY AND SAFETY OF DAAS TREATMENT IN HUMAN IMMUNODEFICIENCY VIRUS/ HEPATITIS C VIRUS CO-INFECTED PATIENTS: REAL-WORLD EXPERIENCE OF TWO MEDICAL CENTER IN CENTRAL TAIWAN 1,4

2,4

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1,4

1

陳宣怡 李原地 許伯格 蘇培元 汪奇志 張秋純 1,4 1 3 1,4 楊子緯 黃士銘 蘇維文 蔡明璋 1 中山醫學大學附設醫院肝膽腸胃科 2 中山醫學大學附設醫院感染科 3 彰化基督教醫院肝膽腸胃科 4 中山醫學大學醫學系

Background: Infection with HCV and HIV is the global burden of disease. There are 37 million people infected with HIV and 115 million people with antibodies to hepatitis C virus globally. The prevalence of CHC among HIV-positive patients in Europe and the USA is mostly in the range of 25–30 %. Recently, two meta-analysis studies revealed consistently higher HCV prevalence in HIV-infected individuals than HIV-negative individuals across all risk groups and regions. Compared to HCV mono-infection, HIV/HCV co-infection was found to be associated with faster liver fibrosis progression and markedly higher risk of developing cirrhosis. In patients infected with HCV alone and co-infected by HIV. In the HCV-monoinfected population, eradication of HCV following antiHCV therapy may reduce the risk of developing type 2 diabetes mellitus, renal and cardiovascular events and neurocognitive dysfunction. In a recent study , Berenguer, Gonz_alez-Garcia, et al. suggest that eradication of HCV in co-infected patients is associated not only with a reduction in the frequency of death, HIV progression, and liverrelated events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure.

Aims: To evaluate the efficacy and safety of DAAs in HIV/ HCV Coinfection patients.

Methods: Objectives: 1. The prevalence of HCV/HIV coinfection patients.

2. The treatment efficacy of HCV eradication (SVR rates, overall survival, liver-related events, nonliver-related non–AIDS-related (NLR-NAR) events: CV events, DM, renal disease and malignancy)

3. The adverse events during HCV eradication Material and methods: Patients: Inclusion criteria: 1. Patients enrolled with HIV/HCV co-infection and under regular follow up during 2018-2019 Exclusion criteria: 1. Age under 18 years old 2. Underlying malignancy 3. H istological evidence of other concomitant chronic liver disease (autoimmune hepatitis, primary biliary cholangitis, Wilson’s disease…)

Outcome measurement: Variables: Age, gender, infection pathways, social economic status , CD4+ T-cell count, HCV RNA load, HCV genotype, liver fibrotic stages, FIB-4 score, CV diseases, CKD stage, diabetes mellitus, substance used Results: A total of 94 HIV/HCV co-infected patients (male/ female: 86.2% /13.8%) with an average age of 44 (21-76) and an average BMI of 23.6 Kg/m2 were enrolled. 22(23%) patients was HCV genotype 1a, 17(18%) patients was genotype 1b, 21(22%) patients was genotype 2, 13(13.8%) was genotype 3(21.2%), 20 was genotype 6, and 1(1%) was mixed genotype. 31(33%) patients were cirrhotic, 63(67%) patients were non-cirrhotic. Mean fibrosis-4 (FIB4) index was 2.53. The mean baseline HCV RNA level was 6.5 log IU/mL. 39(41.5%) patients received pangenotypic DAA treatment and 55(58.5%) patients received non-pangenotypic DAA treatment. 36 patients received pangenotypic DAA treatment for scheduled 8 weeks. All (100%) patients underwent antiretroviral therapy before initiated HCV therapy. No patient initiated HCV therapy with absolute CD4 cell counts more than 350 cells/mm3.

The sustained virologic response (SVR) at week 12 were 97.9% (92/94). Two patients who did not achieved SVR12 were HCV genotype 3 and 6 and both received nonpangenotypic DAA regimen. There was no drug-related severe adverse event reported. No adverse events leading to discontinuation of treatment was observed.

Conclusions: In our real-world experience, the DAAs treatment is well tolerable and had high SVR12 rate in HIV/HCV coinfection patients.

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P.033

P.034

全基因型 C 型肝炎口服抗病毒藥物在台灣 真實世界的療效和安全性 PANGENOTYPIC DIRECT-ACTING ANTIVIRALS FOR PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: REAL-WORLD EFFECTIVENESS AND SAFETY IN TAIWAN

慢 性 C 型 肝 炎 患 者 接 受 Sofosbuvir/ Velpatasvir 治療後之腎功能變化 CHANGES IN RENAL FUNCTION IN CHRONIC HEPATITIS C PATIENTS TREATED WITH SOFOSBUVIR/ VELPATASVIR

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方冠傑 高偉育 蘇建維 唐瑞祥 張君照 張甄 1 臺北醫學大學附設醫院 2 臺北榮民總醫院

Background: Sofosbuvir+Velpatasvir (SOF/VEL) and Glecaprevir/pibrentasvir (GLE/PIB) were two main pangenotypic direct-acting antiviral agents for the treatment of chronic hepatitis C virus (HCV) infection in Taiwan.

However, real-world data of SOF/VEL and GLE/PIB in Asian patients are limited.

Aims: Therefore, our study tried to investigate the effectiveness and safety of these two pangenotypic DAA regimens in Taiwanese patients with chronic hepatitis.

Methods: We performed a retrospective study on 86 CHC patients. 15 patients were treated with SOF/VEL and 71 patients were treated with GLE/PIB. CHC patients who received GLE/PIB and SOF/VEL since October of 2018 to August of 2019 were consecutively enrolled. The treatment duration was determined according to drug label.

The primary endpoint was undetectable HCV RNA (an HCV RNA level of <25 IU/mL) at 12 weeks posttreatment (SVR12). The safety profiles were also assessed.

Results: A total of 86 CHC patients with 52.3% of males were enrolled. The median age was 57 years. A majority (37%) of patients were infected with HCV genotype 2.

The overall SVR12 rates were 100% in both group.

The adverse events (AEs) were pruritus (1.2%) and headache (1.2%). One patient died from non-drug effects.

Conclusions: Interferon-free pan-genotype direct-acting antiviral regimen is highly effective and safe for Asian chronic hepatitis C patients Further large cohort long-term effects of DAA therapy studies are warranted.

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吳璟淇 董水義 魏國良 張德生 盧勝男 洪肇宏 1 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科 2 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 Background: The association of sofosbuvir (SOF)-based regimen and renal toxicity remains controversial .

Aims: This study aimed to evaluate the changes of estimated glomerular filtration rate (eGFR) and the evolution of chronic kidney disease (CKD) stage in chronic hepatitis C patient treated with SOF/VEL in a real-world setting.

Methods: A total of 111 patients receiving SOF/VEL with (n=11) or without (n=100) ribavirin for 12 weeks were retrospectively enrolled. The eGFR was assessed at baseline, week 4, end of treatment and 12 weeks after completion. Progression of chronic kidney disease (CKD) stage was defined as an increase of at least one stage in the course.

Results: There were no significant changes in mean estimated GFR between baseline (77.9+/-28.2 mL/ min/1.73 m2) and week 4 (78.1+/-21.8 mL/min/1.73 m2), end of treatment (77.4+/-24.3 mL/min/1.73 m2) and 12 weeks after completion (76.7+/-23.8 mL/min/1.73 m 2).

At week 4, CKD stage progressed in 14 (16.5%) of the patients, stabilized in 59 (69.4%), and improved in 12 (14.1%); while at end of treatment, CKD stage progressed in 14 (14.3%) of the patients, stabilized in 66 (67.3%), and improved in 18 (18.4%). By 1 Jan June 2020, 6 of 45 (13.3%) patients had CKD stage progression at 12 weeks off therapy. Multivariate analysis showed that liver cirrhosis (odds ratio [OR]=3.62, 95% confidence interval [CI]: 1.0712.26, p=0.038) and higher aspartate aminotransferase (OR=1.01, 95% CI: 1.00-102; p=0.052) were significant factors associated with CKD stage progression at end of treatment.

Conclusions: Despite no significant changes of mean estimated GFR, a small portion of patients had CKD stage progression at 12 weeks off SOF/VEL therapy. Close monitoring of renal function is recommended in patients receiving SOF/VEL, especially in cirrhotic patients.

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P.035

P.036

DAA 治療肝癌的 SVR 高，肝癌的發生率及 復發率都低 GOOD SVR RATE IN HCV-RELATED HCC, AND LOWER OCCURRENCE AND RECURRENCE OF HCC AFTER DAA THERAPY IN 2584 PATIENTS.

GP 在慢性腎病及洗腎 C 肝病人的療效及安 全性 EFFICACY AND SAFETY OF GECAPREVIR/PIBRENTASVIR IN HCV PATIENTS WITH CKD :SVR IN CKD WITH OR WITHOUT HEMODIALYSIS.

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

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: There were great improvements in DAA treatment SVR in HCV patients. The real world effectiveness and safety of DAA in patients with HCVrelated hepatocellular carcinoma (HCC) has not been investigated.

Aims: We evaluated the real-world effectiveness and safety of DAA treatment in HCV-related HCC. Methods: From 2017 to 2019, all patients admitted to our institution with HCV-related HCC were examined to determine the types and outcome of DAA therapy, modalities of HCC treatment, status of HCC during DAA treatment, and change of liver function after DAA treatment.

Results: Among the 244 HCV-related HCC patients treated with DAAs, the SVR rate was 97.9%. Only 5 HCC patients without SVR were noted with one death (20%). There were 239 patients with SVR and 4 patients (1.6%) died after SVR. Totally, 36 patients failed to SVR in 2584 DAAtreated HCV (36/2584=1.4%) 3 HCC (3/36=8.3%) occurred in DAA-failed HCV patients.54 HCC (54/2340=2.3%) occurred in HCV patients received DAA therapy with SVR rate 94.4% (51/54). Unfortunately, the 54 patients developed naive HCC with a median 12 months (range: 3-43 months) after HCV treatment. After DAA treatment, liver function improved from Child-Pugh class B to A in 38.5%. Among the HCV-related HCC with curative therapy and complete response, the HCC recurrence rate was 57.4%. The medium time to HCC recurrence was 7 months after DAA treatment.

Conclusions: DAA treatment of patients with HCC was not inferior to general HCV patients without HCC in term of efficacy and safety. Close surveillance of HCC patients is needed for those with advanced fibrosis and cirrhosis soon after complete DAA treatment.

Background: Direct-acting antivirals (DAAs) have markedly improved the effectiveness of anti-viral therapy for chronic hepatitis C (CHC) patients. 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. In Taiwan, the NS3/4A protease inhibitor glecaprevir(G) and the NS5 inhibitor pibrentasvir(P) had been clinically applied since Aug 2018. Limited real-world evidences of GP in CKD patients with HCV in high prevalent Chia-Yi, Taiwan are available.

Aims: Our prospective study investigate the efficacy and safety of GP therapy in CHC patients with CKD or hemodialysis.

Methods: CHC patients treated with Glecaprevir/ Pibrentasvir between 2018-2019 were subjected to present analysis. We prospectively collected all 8 or 12 weeks treatment of GP in CKD with or without hemodialysis according to cirrhosis.

Results: Of 2584 chronic hepatitis C patients ,156 had CKD(48) or uremia with hemodialysis (108). Patients with genotype 1b, 2 , 1+2 and 6 were 72,80,3,1. The overall SVR rate was 98.1%. All of the patients with cirrhosis with renal function impairment achieved SVR. The SVR rate in CKD patients with dialysis were 98.1% (106/108) and in patients without dialysis were 97.9% (47/48). No relapse or reinfection was found. eGFR levels were ot decreased from the baseline to SVR (post 12 weeks). The most common adverse event was pruritus. Only one itching related discontinuation was noted. The withdrawal rate was 0.6%. One death during GP therapy was revealed in uremia patients due to sepsis. The mortality rate of GP in uremic patients was 0.9%.

Conclusions: The present prospective study demonstrated that Glecaprevir/Pibrentasvir is highly effective and safe for chronic hepatitis C patients with CKD and hemodialysis.

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P.037

P.038

口服抗病毒藥物清除Ｃ肝病毒後可降低過 氧化壓力 – 初報 REDUCING OXIDATIVE STRESS FOLLOWING HCV CLEARANCE BY DIRECT ACTING ANTIVIRALS – A PRELIMINARY RESULT

使 用 Paritaprevir/Ritonavir、ombitasvir 和 dasabuvir 治療的慢性 C 型肝炎過程中引起 高膽紅素血症的誘發因子 PRECIPITATING FACTORS THAT CAUSE HYPERBILIRUBINEMIA IN CHRONIC HEPATITIS C TREATED WITH PARITAPREVIR/RITONAVIR, OMBITASVIR, AND DASABUVIR

1

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鄭斌男 孫宏羽 楊孔家 1 成功大學醫學院附設醫院內科部 2 成功大學醫學院醫學生物技術學系 Background: Chronic hepatitis C (CHC) predisposes to hepatic and extrahepatic diseases, and various kinds of metabolic dysregulations. The overwhelming viral infection-induced reactive oxygen species (ROS) overload that attack the intracellular macromolecules contributes as a factor of HCV pathogenesis and disease progression.

The dynamics of ROS following HCV clearance by direct acting antivirals (DAA) warrants investigation.

Aims: To investigate the short-term and long‐term changes of oxidative DNA damage, oxidative lipid markers, and protein oxidation/nitration before and following SVR by DAA Methods: In total of 20 CHC patients received DAA treatment were enrolled. Markers of ROS including 8-hydroxydeoxyguanosine (8-oxodG) and oxidized lowdensity lipoprotein (LDL) were analyzed before DAA treatment, SVR12, and 12 months following SVR12.

Results: All of the 20 patients (7 males and 13 females) achieved SVR12. Significant decline of levels of 8-oxodG from baseline (16846 ± 6093 ng/mL), SVR12 (14112 ± 3833 ng/mL; p =0.0282 for comparison with baseline), and 12 months following SVR12 (14773 ± 4817 ng/mL; p =0.0156 for comparison with baseline) was present.

Significant decline of levels of oxidized LDL from baseline (13165 ± 8443 ng/mL), SVR12 (11146 ± 6503 ng/mL; p =0.0096 for comparison with baseline), and 12 months following SVR12 (10037 ± 4717 ng/mL; p =0.0409 for comparison with baseline) was present.

Conclusions: Oxidative stress was reduced following SVR12 and persisted for one year. The results indicate the redox homeostasis may recover immediately after HCV clearance and maintain at least for one year thereafter.

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王怡凱 李偉平 藍耿欣 黃怡翔 侯明志 1 臺北榮民總醫院藥劑部 2 臺北榮民總醫院醫學研究部 3 臺北榮民總醫院內科部胃腸肝膽科 4 臺北榮民總醫院內科部

Background: Hepatic decompensation is a fatal ontreatment side effect in chronic hepatitis C treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD).

Rapid elevation of bilirubin may lead to hepatic failure in susceptible patients. Therefore, to find clinical parameters that precipitate the occurrence of early elevation of bilirubin may contribute to the prescription of the regimen.

Aims: To evaluate the precipitating factors resulting in hyperbilirubinemia in chronic hepatitis C patients treated with paritaprevir/ritonavir, ombitasvir, and dasabuvir Methods: A retrospective study was performed to analyze 169 HCV-genotype 1b patients receiving PrOD with or without ribavirin (RBV) for 12 weeks. Laboratory data were analyzed by χ2 with Fisher’s exact test to determine the precipitating factors that caused total bilirubin > 2 mg/ dL in these patients who had received one week of PrOD treatment.

Results: At 12weeks after the end of treatment, SVR was achieved by 164 patients (97.0%). One patient had pretreatment hyperbilirubinemia (total bilirubin >2 mg/dL, 0.6%). 36 patients had total bilirubin >2 mg/dL (21.3%) after one week of treatment. Pre-treatment platelet <100000/ul correlated with total bilirubin >2 mg/dL after one week of treatment (RR: 8.33, 95% CI: 3.57-20.00, p<0.001), and so did F3/F4 fibrosis (RR: 10.42, 95% CI: 3.79-28.65, p<0.001). Addition of RBV to PrOD increased risk of hyperbilirubinemia. Within F3/F4 fibrosis group, pre-treatment platelet < 100000/ul also correlated with total bilirubin >2 mg/dL after one week of treatment (RR: 3.57, 95% CI: 1.35-9.09, p=0.010).

Conclusions: PrOD is an effective direct-acting antiviral regimen in HCV genotype 1b patients. Total bilirubin >2 mg/dL after one week of treatment is the early warning of

2020 消化系聯合學術演講年會

P.039 irreversible progression to hepatic decompensation. This serious adverse event is not common but needs to take caution during PrOD prescription in patients with platelet count < 100000/ul and F3/F4 fibrosis.

C 型肝炎口服抗病毒藥物在中台灣實際效果 評估 REAL-WORLD EFFECTIVENESS OF DIRECT-ACTING ANTIVIRAL AGENTS FOR CHRONIC HEPATITIS C IN CENTRAL OF TAIWAN 李秉桓 臺中榮民總醫院 Background: Since January, 2018, all patients who were HCV RNA positive more than 6 months under DAA regimens became easily accessible by NHI, however realworld population-based analyses were few in real-life results.

Aims: real-world population-based analyses in central of Taiwan Methods: Retrospective study on 400 CHC patients. The primary endpoint was undetectable HCV RNA (an HCV RNA level of <25 IU/mL) at 12 weeks posttreatment (SVR12).

Results: Genotype 1b was the major genotype (371, 67%), followed by genotype 2 (139, 25%). The patients were treated according to HCV genotype, clinical practice and reimbursement guidelines. The SVR12 rates of 111 patients treated with Harvoni+, 151 treated with Viekirax+Exviera, 86 treated with Zepatier+ were 100%, 92.72% and 100.0%, respectively Conclusions: The effect of DAA was reliable in real world data

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P.040

P.041

以 glecaprevir/pibrentasvir 對全基因型 C 型 肝炎治療之臨床治療成效及安全性經驗 EFFICACY AND SAFETY OF GLECAPREVIR/PIBRENTASVIR FOR PANGENOTYPIC CHRONIC HEPATITIS C PATIENTS - A REAL-WORLD EXPERIENCE OF SINGLE MEDICAL CENTER IN NORTH TAIWAN

台灣 C 型肝炎清除：一山地地區模式 A MODEL OF MICRO-ELIMINATION: A HEPATITIS C HYPERENDEMIC ABORIGINAL TOWNSHIP IN TAIWAN

蔡宗憲 王蒼恩 陳銘仁 朱正心 張經緯 王鴻源 馬偕紀念醫院腸胃內科 馬偕醫護管理專科學校 馬偕醫學院 Background: Glecaprevir/pibrentasvir (GLE/PIB), the direct-acting antiviral agent for the treatment of CHC, is the first pangenotypic regimen licensed in Taiwan. However, real-world data of GLE/PIB in Taiwan are limited.

Aims: This study is aimed to analysis the real-world experience in treatment for the real-world experience of single medical center in Taiwan for analysis for efficacy and safety of glecaprevir/pibrentasvir for pangenotypic chronic hepatitis C patients Methods: From September 2018 to July 2019 in MacKay Memorial Hospital, Taipei and Tamsui branch, we retrospectively reviewed 90 patients with CHC who underwent HCV eradication therapy with GLE/PIB. The primary endpoint was the rate of sustained virologic response at week 12 off therapy (SVR-12).

Results: Among 90 patients, 6 patients lost follow-up for personal factors. A total of 84 CHC patients were analysed (per-protocol). The median age was 61.49 years old and 44(52%) patients were males. There are 19 patients (23%) with liver cirrhosis, and 15 patients (11%) with chronic kidney disease stage IV-V. The other baseline characteristics of patients are listed as table 1. For all the patients, type 2 HCV hepatitis is most common for patients received glecaprevir/pibrentasvir for HCV eradication.

The common AEs were insomnia(17%), abdominal discomfort(17%), fatigue(12%) and pruritus(11%). None had hepatic decompensation or death.

Conclusions: GLE/PIB regimen is effective and safe for pangenotypic CHC patients even with compensated cirrhosis or chronic kidney disease stages 4-5.

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1,2

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戴嘉言 黃駿逸 梁博程 葉明倫 黃釧峰 1,2 1,2 4 1,2 黃志富 莊萬龍 邱孟肇 余明隆 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學系內科 3 高雄醫學大學附設醫院社區醫學部 4 高雄市桃源區衛生所

1,2

Background: In Taiwan, several hyperendemic townships with prevalence of anti-hepatitis C virus (HCV) more than 10% have been explored, including Tau-Yuan Township (TYT) in high mountain area of Kaohsiung. With the WHO goal to eliminate the chronic hepatitis by 2030, the Ministry of Health and Welfare in Taiwan have declared to firstly launch the micro-elimination of the hyperendemic aboriginal townships since August, 2018.

Aims: The aim of the study is to evaluate the effectiveness of an outreach people-centered screening and treater program for HCV micro-elimination in TYT Methods: In TYT, the project underwent with the goals: For the registered residents aged 30-75 years who live in TYT more than 6 months in a year (frequent living residents, FLR), the screening rate for HCV seromarkers more than 80%, and more than 80% of the definitely diagnosed viremic patients linked to receive DAAs therapy.

The accessible clinical care including screening, diagnosis and treatment is supported by the Health Center of TYT and Kaohsiung Medical University Hospital Results: Of overall 4317 registered residents, 2516 aged 30-75 years and 1073 fulfill the criteria of FLR in TYT as the target population. The clinical data were collected and screening launched for patients who are unawareness the status of anti-HCV status. By the end of Oct 2019, 1072 (99.9%) were completed for the screening (one resident expired). Of the patients with HCV viremia, they were referred to receive treatment by the regional hospitals, the medical centers in Kaohsiung city or in the Health Center of TYT according patients’ willing. By Oct. 2019, 127 anti-HCV positive patients were all tested for HCV RNA (100%) and 77 (61%) of the 127 patients were seropositive for HCV RNA. Fourty, 31 and 6 patients were treated in Health Center of TYT, other hospital and without treatment, respectively, with an overall treatment rate of 92.2%. Thirty-seven of the 40 patients (3 still with

2020 消化系聯合學術演講年會

P.042 treatment) treated in TYT and 31 patients treated in other hospital have completed 12 weeks posttreatment follow-up and all achieved SVR12.

Conclusions: In this real-world micro-elimination project of a hepatitis C hyperendemic aboriginal township in Taiwan, the goal of HCV micro-elimination could be achieved by implementation of a people-centered outreach screening and treater program to improve the ability of link-to-diagnosis and link-to-treat in local Health Center.

This model is believed to represent a standard of care cascade in hyperenemic areas in Taiwan and even all over the world.

Eritoran 減輕了慢性四氯化碳損傷小鼠的肝 纖維化 ERITORAN ATTENUATED LIVER FIBROSIS IN MICE WITH CHRONIC CARBON TETRACHLORIDE INJURY 1,2

1,2

1,2

1,2

1,2

李癸汌 謝昀蓁 黃怡翔 侯明志 林漢傑 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學內科學科

Background: Gene knockout of TLR4 has a protective effect on liver injury. TLR4 inhibitor, eritoran tetrasodium was found to reduce IL-6 levels and less NF-κB activation to prevent intestinal barrier permeability and reduce liver damage in resuscitated acute hemorrhagic shock mice.

Aims: However, the effects of eritoran on gut-liver axis of chronic liver injury have not been reported.

Methods: Intraperitoneal injection of carbon tetrachloride (0.5 mg/kg, twice weekly) for 8 weeks in C57BL6 mice was used to produce leaky gut and chronic liver injury.

Mice injected with cotton oil served as normal controls.

The mice with or without chronic liver injury received intraperitoneal injection of eritoran tetrasodium (5 mg/kg twice a week) or placebo for 4 weeks to evaluate the effects on intestinal permeability, bacterial displacement and liver fibrosis.

Results: Eritoran improved liver fibrosis, reduced the expression levels of tissue growth factor beta 1 and MyD88, and decreased the nuclear translocation of nuclear factor kappa B p65. However, there was no significant effect on intestinal permeability and intestinal bacterial displacement and liver inflammation.

Conclusions: In mice with carbon tetrachloride injury, although chronic TLR4 inhibitor treatment did not improve intestinal permeability and intestinal bacterial displacement and hepatic inflammation, it attenuated liver fibrosis significantly. Therefore, we will use the TLR4 inhibitor to investigate its effect on liver fibrosis in another animal model and perform some in vitro studies to elucidate the underlying mechanisms of its antifibrotic effect, in order to provide a strong basis for possible clinical application.

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P.043

P.044

肝星狀細胞之腎素原受體抑制可透過 ERK/ TGF-β1/SMAD3 路徑之不活化改善小鼠肝 纖維化 HEPATIC STELLATE CELL-SPECIFIC (PRO)RENIN RECEPTOR KNOCKDOWN ATTENUATES LIVER FIBROSIS THROUGH INACTIVATION OF ERK/ TGF-β1/SMAD3 PATHWAY

β 交感神經受體阻斷劑對於代償性肝硬化病 人預後的角色。 THE ROLE OF NON-SELECTIVE ꞵ– BLOCKERS IN COMPENSATED CIRRHOTIC PATIENTS WITHOUT MAJOR COMPLICATIONS

謝昀蓁 李癸汌 藍耿欣 霍德義 黃怡翔 侯明志 林漢傑 臺北榮民總醫院胃腸科 Background: The (pro)renin receptor (PRR) activation upregulates the expression of profibrotic genes in kidney and heart.

Aims: We aimed to investigate the role of PRR in hepatic fibrogenesis.

Methods: Primary mouse hepatic stellate cells (HSCs) were isolated for PRR expression analysis. Experimental fibrosis was studied in thioacetamide (TAA)-treated or methionine choline-deficient (MCD) diet-fed C57BL/6 mice. A lentiviral vector expressing PRR short hairpin RNA (shRNA) from the α-smooth muscle actin promoter was used for HSC-specific gene knockdown. Lentivirusmediated PRR shRNA was used to knockdown the PRR expression in human HSCs cell line, LX-2.

Results: The PRR is upregulated in the mouse fibrotic livers and in vitro and in vivo activated HSCs. The HSCspecific PRR knockdown attenuated liver fibrosis in TAA or MCD diet-injured mice with the suppression of HSC activation and profibrotic genes expression. Mice with HSC-specific PRR knockdown downregulated the hepatic ERK1/2-TGF-β1/Smad3 pathway. Renin or prorenin induced an increase expression of PRR and production of TGF-β1 in LX-2 cells and knockdown of PRR inactivated LX-2 cells with blocking production of TGF-β1 and Smad3 phosphorylation.

Conclusions: (Pro)renin receptor is upregulated in fibrotic livers and activated HSCs, and its downregulation attenuates liver fibrosis through inactivation of ERK1/2TGF-β1/Smad3 pathway. Thus, PRR is a promising therapeutic target for liver fibrosis.

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吳鎮琨 楊世正 梁志明 李育騏 葉文碩 戴維震 1, 2 3 1, 2 吳耿良 許茜甯 蔡成枝 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院 3 長庚醫療財團法人高雄長庚紀念醫院藥劑部 Background: Non-selective ꞵ–blockers (NSBB) could prevent decompensation and hepatocellular carcinoma (HCC) in cirrhotic patients with clinically significant portal hypertension (CSPH) but remained uncertain for compensated cirrhotic patients without major complications.

Aims: We aimed to compare the clinical outcomes between propranolol users and non-users of CC group without major complications.

Methods: We conducted this population-based cohort study by using Taiwanese Longitudinal Health Insurance Database 2000. Propranolol users (classified as cumulative defined daily dose (cDDD)) and non-PPL users were matched 1:1 propensity score in both cohorts.

Results: This study comprised 6896 propranolol users and 6896 non- propranolol users. There was no significant impact on the development of spontaneous bacterial peritonitis between the two groups (aHR: 1.24, 95% CI: 0.88~1.75; p=0.2111). As for mortality, male gender, aged condition and non-liver related diseases (peripheral vascular disease, cerebrovascular disease, dementia, pulmonary disease, renal disease) were the independent risk factors of mortality. PPL users had significantly lower incidence of HCC development than non-users (aHR: 0.81, p = 0.0580; aHR: 0.80, p = 0.1588; and aHR: 0.49, p<0.0001 in the groups of 1-28, 29–90, and >90 cDDD, respectively).

Conclusions: Current study suggested that high cumulative doses of propranolol could decreased the risk of hepatocellular carcinoma among compensated cirrhotic patients without major complications. Further large-scale prospective studies are still required to confirm the finding in this study.

2020 消化系聯合學術演講年會

P.045

P.046

心臟舒張功能障礙的早期心臟超音波變化 預測肝硬化病患之急性腎損傷 EARLY ECHOCARDIOGRAPHIC SIGNS OF DIASTOLIC DYSFUNCTION PREDICT ACUTE KIDNEY INJURY IN CIRRHOTIC PATIENTS

肝硬化回復之長期過程：經由 sofosbuvirbased 藥物成功治療之 C 型肝炎肝硬化患者 之經驗觀察 LONG-TERM COURSE OF CIRRHOSIS REGRESSION: LESSONS FROM PATIENTS WITH HCV CIRRHOSIS FOLLOWING SUCCESSFUL SOFOSBUVIR-BASED TREATMENT

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1,2

2,3

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吳佩珊 李癸汌 謝昀蓁 李沛璋 黃金洲 黃怡翔 1,2 1,2 侯明志 林漢傑 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學 3 臺北榮民總醫院心臟內科

Background: Cardiovascular dysfunction in cirrhotic patients influences survival and the development of cirrhotic complications.

Aims: We aimed to evaluate potential echocardiographic parameters to predict mortality and acute kidney injury (AKI) in cirrhotic patients.

Methods: Total 103 cirrhotic patients receiving echocardiography between February 2009 and August 2016 in Taipei Veterans General Hospital were retrospectively enrolled. The cardiac function was evaluated using transthoracic two-dimensional echocardiography with tissue Doppler imaging. Cox hazard regression analysis was used for assessing predictors for one-year mortality and AKI. Results: The baseline echocardiographic parameters were similar between survivors (n= 92) and non-survivors (n= 11). Lower serum levels of albumin, higher Child-Pugh scores, and higher MELD scores were observed in nonsurvivors. On Cox hazard regression analysis, ChildPugh score was the only predictor for one-year mortality.

Baseline serum Cr > 1.5 mg/dL, TB > 2 mg/dL and a higher E/e’ ratio predict occurrence of AKI. In patients with serum Cr < 1.5 mg/dL, an increased atrial filling velocity and higher MELD scores predict AKI occurrence, which remained significant after excluding patients with CAD. Conclusions: The severity of underlying liver disease but not echocardiographic parameters predicts one-year mortality in cirrhosis. An increased atrial filling velocity and higher MELD scores predict AKI in those with serum Cr < 1.5 mg/dL. Early echocardiographic signs of diastolic dysfunction may predict development of acute kidney injury in cirrhotic patients with serum Cr < 1.5 mg/dL.

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Ira Jacobson , Andrew J. Muir , Eric Lawitz , Edward 4 5 6 7 Gane , Brian Conway , Peter J. Ruane , Ziad Younes , 8 8 Frances Chen , Marianne Camargo , Anand P. 8 8 8 Chokkalingam , C. Stephen Djedjos , Anuj Gaggar , 8 9 10 Robert P. Myers , Barbara Leggett , Jose Luis Calleja , 11 12 13 Kosh Agarwal , K. Rajender Reddy , Alessandra Mangia 1 NYU Langone Health, New York, NY, USA 2 Duke University, Durham, NC, USA Texas Liver Institute, University of Texas Health San 3 Antonio, TX, USA New Zealand Liver Transplant Unit, Auckland City 4 Hospital, Auckland, New Zealand Vancouver Infectious Diseases Centre, Vancouver, BC, 5 Canada Ruane Medical & Liver Health Institute, Los Angeles, CA, 6 USA 7 GastroOne, Germantown, TN, USA 8 Gilead Sciences, Inc., Foster City, CA, USA School of Medicine, University of Queensland, Brisbane, 9 Australia 10 Hospital Universitario Puerta de Hierro, Madrid, Spain Kings College Hospital NHS Trust Foundation, London, 11 UK 12 University of Pennsylvania, Philadelphia, PA, USA Casa Sollievo della Sofferenza Hospital, San Giovanni 13 Rotondo, Italy Background: In patients with HCV cirrhosis, a sustained virologic response (SVR) to antiviral therapy is associated with improved clinical outcomes; however, the temporal course of changes in fibrosis is poorly understood. Our aim was to evaluate changes in noninvasive tests of fibrosis (NITs) in this setting to gain insights into the natural history of cirrhosis regression following removal of the causative exposure.

Aims: To evaluate changes in noninvasive tests of fibrosis (NITs) in this setting to gain insights into the natural history of cirrhosis regression following removal of the causative exposure.

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P.047 Methods: We studied patients with HCV cirrhosis who achieved SVR with sofosbuvir (SOF)-based regimens (in a trial or clinical practice) in an ongoing, prospective cirrhosis registry (NCT02292706). Patients underwent routine clinical and laboratory assessments, including semi-annual Child-Pugh-Turcotte (CPT) scoring and measurement of the Enhanced Liver Fibrosis (ELF) test, as well as annual liver stiffness measurement by transient elastography (LS by TE). Changes in fibrosis were estimated based on ELF response (defined as ≥0.5 unit reduction), and shifts in estimated fibrosis categories based on ELF (F3, ELF 9.8-11.3; F4, ELF >11.3) and LS by TE (F3, 9.6-12.5 kPa; F4, >12.5 kPa). Logistic regression was used to identify predictors of fibrosis improvement as defined by NITs. Results: 1,574 subjects with HCV cirrhosis (32% female, 39% BMI ≥30 kg/m2, 7% CPT class B/C) were included in this study; median interval between SVR and registry enrollment was 38 weeks (IQR 27-60). At enrollment, median (IQR) ELF was 14.3 (9.5, 22.1); 586 (37%) and 247 (16%) patients had ELF scores consistent with F3 and F4 fibrosis, respectively. Median LS by TE was 9.9 kPa (9.2, 10.8); 761 (57%) and 227 (17%) patients had LS consistent with F3 and F4 fibrosis, respectively. As of May 2019, median duration of follow-up after registry enrollment was 123 weeks (IQR 96, 168). At week 144, 49% of those with baseline CPT class B/C had improved CPT class, while 98% of those with baseline CPT class A remained in CPT class A. During follow-up, changes in ELF and LS by TE suggested fibrosis improvement in an increasing proportion of patients with both F3 and F4 fibrosis at enrollment (Figure). ELF score improved by >0.5 units at week 144 in 27% and 47% of patients with baseline F3 and F4 fibrosis, respectively. Predictors of ELF improvement included higher ELF (p<0.001) and AST (p=0.049), and lower platelets (p=0.02) and BMI (p=0.10) at registry baseline.

Conclusions: In patients with cirrhosis in whom HCV has been eradicated by SOF-based therapy, NITs suggest significant fibrosis improvement in 25-50% of patients within 3 years. Associations between reductions in these NITs and improvements in clinical outcomes require evaluation during longer-term follow-up.

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二維超音波彈性度檢查診斷肝纖維化程度 的效用 - 以瞬時彈性度檢查為標準 THE USEFULNESS OF TWODIMENSIONAL SHEAR WAVE ULTRASOUND ELASTOGRAPHY IN ASSESSING HEPATIC FIBROSIS FOR CHRONIC VIRAL HEPATITIS USING TRANSIENT ELASTOGRAPHY AS REFERENCE 王景弘 顏毅豪 張國欽 郭垣宏 胡琮輝 陳建宏 盧勝男 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 Background: Transient elastography (TE) is the standard of liver stiffness in hepatic fibrosis assessment.

Aims: his study aimed to evaluate the usefulness of twodimensional shear wave elastography (2D-SWE) in assessing hepatic fibrosis with transient elastography as reference.

Methods: Patients with chronic hepatitis B (CHB) or C (CHC) scheduled for liver ultrasonography (US) and TE at the same morning was enrolled prospectively. As the reference, TE (Fibroscan™; Echosens, Paris, France) was performed to determine the fibrosis stage (F) by an experienced technician without knowledge of results of US and 2D-SWE. In addition to liver US, 2D-SWE (Elast Q, EPIQ 7G, Philips, USA) were performed to determine liver stiffness. Before this study, one hepatologist with experienced US exam performed 2D-SWE after training by manufacture and experiences in 130 patients of 2D-SWE. Stratified by TE values, the F0-1 value was <7.5kPa, F2 7.5-9.4kPa, F3 9.5-12.5 and F4 >12.5kPa for CHC, and <7.2kPa, 7.2-8.0kPa, 8.1-11kPa and >11 kPa for CHB. The performance of 2D-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 2019/11, a total of 1073 patients was enrolled, including 623 with CHC and 450 with CHB. The correlations between 2D SWE and TE were 0.791, 0.820 and 0.738 for total patients, CHC and CHB. Stratified by TE, there are 322 (51.7%), 91 (14.6%), 74(11.9%) and 136 (21.8%) with F0/1, F2, F3 and >F4 for CHC, and 262 (58.1%), 41 (9.1%), 63 (14%) and 84 (18.7%) for CHB. While the median values were 5.6 for F0-1, 6.9 for F2, 9.0 for F3 and 12.6kPa for F4 for CHC, they were 5.6, 6.2, 8.6 and 12kPa for CHB (r=0.761, p<0.001; r=0.709, p<0.001). The performance of 2D SWE in diagnosing >=F2, >=F3 and F4 were 0.895, 0.923 and

2020 消化系聯合學術演講年會

P.048 0.957 for CHC, and 0.878, 0.918 and 0.946 for CHB. The cutoff of 2D SWE in diagnosing >=F2, >=F3 and F4 were 6.8, 7.6 and 10.3kPa with sensitivity/specificity 89.5/79.7%, 92.3/87.1% and 95.7/90.4% for CHC, and 6.7, 7.8, and 9.9 with 77.1/86.3%, 80.3/90.8% and 83.3/91.8% for CHB. Conclusions: 2D-SWE by ELAST Q correlated with TE in liver stiffness measurement for patients with chronic viral hepatitis It was useful in the diagnosis of severe fibrosis and cirrhosis.

建立以白蛋白 - 膽紅素等級為基準的預後模 型用於預測在米蘭標準內的肝細胞癌患者 的預後 AN ALBUMIN-BILIRUBIN (ALBI) GRADE–BASED PROGNOSTIC MODEL FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA WITHIN MILAN CRITERIA 1,2

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何樹仁 柯智傑 蘇建維 黃怡翔 1,2,5 霍德義 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學院醫學系 3 國立陽明大學醫學院臨床醫學所 4 國立陽明大學醫學院藥理醫學所 5 臺北榮民總醫院醫學研究部

侯明志

1,2

Background: The Milan criteria are recommended as the major reference for liver transplantation in patients with small hepatocellular carcinoma (HCC). However, alternative anticancer treatments are often utilized due to severe donor organ shortage.

Aims: This study aimed to develop and validate an albuminbilirubin (ALBI) grade–based prognostic model to stratify survival in patients within Milan criteria undergoing nontransplant therapy.

Methods: A total of 1655 patients were assigned into the derivation and validation cohort according to treatment modalities. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort.

An ALBI-based model was evaluated in the validation cohort.

Results: In the Cox multivariate model, age 65 years or older (hazard ratio [HR]= 1.576, P< 0.001), serum α-fetoprotein (AFP) level > 100 ng/mL (HR=1.671, P<0.001), ascites (HR= 1.808, P<0.001), performance status 1 to 4 (HR=1.738, P< 0.001), ALBI grade 2 (HR=1.827, P< 0.001), and ALBI grade 3 (HR=3.589, P<0.001) were independent predictors of poor survival in the derivation cohort. An ALBI-based prognostic model with a total of 0 to 6 points was derived with the sum of 5 variables: 1 point each for age 65 years or older, AFP >100 ng/mL, presence of ascites, performance status 1 to 4, and ALBI grade 2, and 2 points for ALBI grade 3. This model can accurately predict long-term outcome in the validation cohort (P<0.001) and discriminate survival in patients stratified by curative and noncurative treatments (both P<0.001).

Conclusions: The proposed ALBI grade–based model is feasible in predicting survival in HCC patients within the Milan criteria, and helps identify high-risk patients who need timely liver transplantation

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P.049

P.050

肝癌患者接受活體肝移植肝內 miR-122 表 達與白介素遺傳多態性相關 HEPATIC MIR-122 EXPRESSION CORRELATED WITH IL-28B GENETIC POLYMORPHISMS IN PATIENTS WITH HCC WHO UNDERWENT LDLT

治療後期肝癌東西方的差異 REAL WORLD CLINICAL PRACTICE IN TREATING ADVANCED HEPATOCELLULAR CARCINOMA: WHEN EAST MEETS WEST

趙景華 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 Background: Hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT) remains problematic. The genetic and molecular characteristics of recipients may affect HCC recurrence.

Aims: We evaluated the effects of microRNA-122 (miR122) and interleukin-28B (IL-28B) genetic polymorphisms on patients with HCC following LDLT. Methods: We prospectively collected 60recipients since September 2016 to August 2018. miR-122 and IL-28B polymorphisms rs8099917 and rs12979860 were evaluated in liver tissues and plasma after LDLT. Results: Hepatitis B virus (HBV), hepatitis C virus (HCV), dual HBV/HCV infection, and non-B non-C were detected in 26, 22, 3, and 9 patients, respectively, over a median follow-up time of 20.5 (10–23) months. No patients showed HCC recurrence after LDLT. miR-122 was significantly higher in the liver tissues than in the plasma of patients with HBV (p = 0.001), HCV (p = 0.002), dual HBV/HCV (p = 0.037), and non-B non-C (p = 0.045). Hepatic miR122 expression was significantly higher for genotype TT (p = 0.006) and genotype TT plus GT (p = 0.005) compared to genotype GG of IL-28B rs8099917 and significantly higher in fatty liver >6% than in <5% (p = 0.000) or no fatty liver (p = 0.001).

Conclusions: High hepatic miR-122 was correlated with the IL-28B rs8099917 genotype TT and GT and with >6% fatty liver, and thus may play a major role in patients with HCC.

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顏毅豪 胡琮輝 鄭汝汾 王景弘 林志哲 1 高雄長庚紀念醫院胃腸肝膽科 2 高雄長庚紀念醫院放射診斷科 3 高雄長庚紀念醫院一般外科

Background: The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafenib is the recommended therapy.

Aims: To investigated the real world clinical treatment and survival of BCLC C patients in an Asian cohort.

Methods: Using the liver cancer registry data for our hospital, we analyzed 427 consecutive BCLC C patients diagnosed between 2011 and 2017. All patients were managed via a multidisciplinary team (MDT) approach.

Results: HBsAg-positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n=83; 19.4%), PS2 alone (n =23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n=321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort, which was longer than that reported in a previous phase III trial of sorafenib in advanced HCC patients conducted in Asia. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type.

Conclusions: We achieved better survival in BCLC C patients through the use of personalized management via a MDT approach.

2020 消化系聯合學術演講年會

P.051

P.052

亞洲一個醫學中心手術切除 BCLC 0, A,B 期肝癌的預後 PROGNOSIS AFTER RESECTION OF BARCELONA CLINIC LIVER CANCER (BCLC) STAGE 0, A, AND B HEPATOCELLULAR CARCINOMA: RESULT FROM AN ASIAN HIGH VOLUME LIVER SURGERY CENTER

保疾伏治療肝細胞癌：台中兩家醫院的合併 經驗 NIVOLUMAB FOR HEPATOCELLULAR CARCINOMA: A COMBINED EXPERIENCE AT TWO HOSPITALS

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顏毅豪 胡琮輝 鄭汝汾 王景弘 林志哲 1 高雄長庚紀念醫院胃腸肝膽科 2 高雄長庚紀念醫院放射診斷科 3 高雄長庚紀念醫院一般外科

Background: In 2011, the original Barcelona Clinic Liver Cancer (BCLC) system was updated to designate a single large hepatocellular carcinoma (HCC) (≥ 5 cm) as BCLC stage A rather than stage B. However, a recent international multi-institutional study from western countries reported that prognosis following liver resection among patients with single large HCC was similar to patients presenting with BCLC-B tumors.

Aims: to evaluate the prognosis following liver resection among patients with single large HCC from an Asian high volume liver surgery center.

Methods: Patients who underwent curative-intent hepatectomy for histologically proven HCC between 2011 and 2017 were enrolled using HCC registry database.

Overall survival (OS) among patients with BCLC stage 0, A, and B was examined. Patients with a single large tumor were classified as BCLC stage A1 and were independently assessed.

Results: Among 543 patients, 89 (16.4%) were BCLC-0, 289 (53.2%) were BCLC-A, 92 (16.9%) were BCLC-A1, and 73 (13.4%) were BCLC-B. Median follow-up was 38 months (26-63). Five-year OS among patients with BCLC stage 0, A, A1, and B HCC was 83.5%, 83.7%, 77.4%, and 55.4%, respectively (log rank test, p<0.001). No difference in OS was noted among patients undergoing surgery for BCLC stage A and A1 HCC (log rank test, p = 0.11), even after adjusting for competing factors (hazard ratio= 1.32, 95% confidence interval= 0.73-2.37; p = 0.36).

Conclusions: Prognosis following liver resection among patients with BCLC-A1 HCC was similar to patients presenting with BCLC-A tumors. The prognosis of single large HCC should be allocated as BCLC stage A

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許偉帆 莊伯恒 陳政國 賴學洲 彭成元 林俊哲 1,5 1,5 黃冠棠 林肇堂 1 中國醫藥大學附設醫院內科部消化系 2 中國醫藥大學生物醫學研究所 3 亞洲大學附屬醫院內科部肝膽腸胃科 4 中國醫藥大學中醫系 5 中國醫藥大學醫學系

1,5

Background: Hepatocellular carcinoma (HCC) is a major health problem in the world. Sorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), is the standard of care for advanced HCC for some years. Recently, lenvatinib, regorafenib, cabozantinib, and ramucirumab have been approved to be the first-line and second-line therapies for advanced HCC in various conditions. However, the prolonged median survival time with these 5 drugs is short.

Immuno-oncology agents (IOs) are emergent therapeutic options for HCC, but the real-world experience of nivolumab for HCC is limited.

Aims: To retrospectively evaluate clinical characters, prior and combination therapy, and adverse effects, and factors associated with objective response to nivolumab in patients with HCC receiving nivolumab therapy.

Methods: From 2012 Feb to 2019 Oct, 84 HCC patients who had received a least one dose of nivolumab were enrolled in this retrospective study from China Medical University Hospital and Asia University Hospital.

Demographic data, virological features, and tumor factors were recorded at the baseline of nivolumab therapy.

Results: Of 84 patients, 76 (90.5%) patients were male, and 50 (59.5%), 21 (25.0%), and 23 (27.4%) patients had chronic hepatitis B, chronic hepatitis C, and alcohol consumption, respectively. 25 (29.8%) and 65 (77.4%) patients had diabetes mellitus and liver cirrhosis, respectively. The median age was 63 (55–69) years (first quartile–third quartile). The ALT, total bilirubin, albumin, AFP, and neutrophil-lymphocyte ratio (NLR) were 53 (30–70) U/L, 1.3 (0.8–2.1) mg/dL, 3.5 (3.0–3.9) g/dL, 340.53 (18.72–7782.50) ng/mL, and 5.37 (3.27–10.25), respectively. 5, 9, 19, and 51 patients belonged to TNM stage I, II, III, and IV, respectively, and 8, 8, 62, and 6 patients belonged to Barcelona Clinic Liver Cancer stage

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P.053 A, B, C, and D, respectively. Most (n = 48, 57.1%) patients had ≥4 hepatic tumors and the median tumor size was 5.3 (2.7–8.2) cm. 50 (59.5%) and 49 (58.3%) patients had extrahepatic metastasis and portal or hepatic vein invasion of HCC, respectively. Most patients received prior (n = 66, 78.6%) and combination therapy (n = 48, 57.1%). The most common combination therapy was tyrosine kinase inhibitor (n = 36, 75%) and then chemotherapy (n = 8, 16.7%).

After excluding 12 patients who were still under nivolumab therapy, the numbers of patients with complete response (CR), partial response (PR), stable disease (SD), progressive disease, and unassessable disease were 6 (7.1%), 6 (7.1%), 15 (17.9%), 24 (28.6%), and 21 (25.0%), respectively. The objective response rate (ORR, CR+PR) and disease control rate (DCR, CR+PR+SD) were 16.7% (12/72) and 37.5% (27/72), respectively. Tumor number (multiple vs. single, hazard ratio [HR] 0.119, 95% confidence interval [CI] 0.022–0.658, p = 0.015), NLR (> 4.75 vs. ≤ 4.75 vs, HR 0.127, 95% CI 0.019–0.864, p = 0.035), and AFP reduction of 20% in the first 3 months of nivolumab therapy (HR 5.172, 95% CI 1.042–25.668, p = 0.044) were independent predictors of ORR for nivolumab in multivariate Cox regression analysis. Four patients expired due to severe immune-related adverse effects (irAEs: 2 hepatitis, 1 pneumonitis, and 1 gastric necrosis).

Conclusions: Nivolumab was effective in a proportion of patients with HCC. Physicians should be aware of irAEs in patients receiving nivolumab therapy. A longer followup period is necessary to identify factors associated with overall survival.

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細胞色素 C 氧化酶過量表現和不好的肝癌 預後有關 OVEREXPRESSION OF CYTOCHROME C OXIDASE SUBUNIT 5B IS RELATED TO POOR PROGNOSIS IN HEPATOCELLULAR CARCINOMA 1,2,3

2

1,2,3

林蔚然 朱育德 葉昭廷 1 林口長庚醫院胃腸肝膽科 2 林口長庚醫院肝臟研究中心 3 長庚大學醫學系 Background: Cytochrome c oxidase (COX), consisted of 13 subunits, is the major regulatory site of oxidative phosphorylation chain in mitochondria.

Aims: The study aims to clarify the prognostic roles of subunits of COX in Hepatocellular carcinoma (HCC).

Methods: Three different cohorts of HCC patients were analyzed. Firstly, the online available GSE63898 and GSE76427 cDNA microarray datasets, were used for genes expression analyses. Secondly, 102 pairs of tumorous and non-tumorous liver tissues were employed for IHC staining. The intensities of IHC staining were scored by two pathologists independently. Thirdly, 157 pairs of patientsderived tumorous and non-tumorous liver tissues were utilized for validation by western blotting and RT-qPCR. All the paired tissues were obtained from Tissue Bank, Chang Gung Memorial Hospital under the permission of the institutional review board. Parametric data were presented as mean ± standard deviation and compared by t-test. Survival analysis was performed by Kaplan-Meier analysis. Patients were grouped as possessing high and low levels of variable(s) for prognostic analyses. Statistical significance was defined as p value < 0.05.

Results: The levels of COX subunits transcripts were analyzed by employing the published GSE63898 and GSE46727 reference datasets. Eight of them, including COX5A, COX5B, COX6A1, COX6B1, COX6C, COX7A2, COX7B, COX7C and COX8A, were significantly elevated in tumor part compared to normal part, while COX7A1 was decreased in the tumorous parts. However, only COX5B revealed a borderline correlation with the overall survival (OS) (p = 0.0606). To examine the correlation between COX5B protein levels and clinical outcome, the samples from a cohort of HCC patients from our institute were assayed. The IHC staining of COX5B using patientderived non-tumorous and tumorous parts of tissues were performed, and the results were scored according to the

2020 消化系聯合學術演講年會

P.054 color intensity. The patients were then divided into two groups by use of the mean of score derived from tumorous part. The lower staining scores of COX5B were associated with a better prognosis in OS, recurrence-free survival (RFS) and metastasis-free survival. Encouraged by these finding, validations were further conducted by use of RNA and protein samples from another independent cohort. The expression of COX5B, either of mRNA or protein, were significantly up-regulated in tumor part. Moreover, when patients were grouped by high and low ratios of COX5B levels in tumorous over non-tumorous parts (T/NT) for survival curve analyses, it was found that those with T/NT ratio ≥ 1 had a poorer OS and RFS. Conclusions: The overexpression of COX5B is associated with poor prognosis in HCC patients, and could be considered as a prognostic marker.

不同設計的穿刺針是否會影響內視鏡超音 波導引下腫瘤診斷結果 ENDOSCOPIC ULTRASONOGRAPHY GUIDED FINE NEEDLE BIOPSY INCREASES THE DIAGNOSTIC YIELD OF MALIGNANCY COMPARED WITH FINE NEEDLE ASPIRATION 1

1,2

1

1

1,2

1,2

鄭煜明 陳建華 蘇偉志 蕭宗賢 徐榮源 趙有誠 1 佛教慈濟醫療財團法人臺北慈濟醫院胃腸肝膽科 2 慈濟大學醫學院

Background: Endoscopic ultrasonography (EUS) guided fine needle aspiration (FNA) is the primary method of pancreatic or gastrointestinal peri-luminal tissue acquisition. With the advent of different design of puncture needle, we don’t know whether the fine needle biopsy (FNB) needle is superior to traditional aspiration needle in the diagnostic yield.

Aims: To improve our yield of EUS-guided tissue acquisition, we use FNB needle for tissue acquisition and assessed the diagnostic yield of FNA and FNB. Methods: This was a retrospective review of our collected data since 2007 to 2019 from consecutive patients who received FNA/B due to pancreatic or gastrointestinal periluminal lesions. A total of 86 patients was recruited and 27 patients underwent FNA from 2007 to 2016, whereas 59 patients received FNB in the following years until now.

FNA needles included 19G, 22G or 25G (EZ shot II®, Olympus, Inc., Tokyo, Japan or Echotip Ultra®, Cook, Inc., Bloomington, IN, U.S.A.). FNB was performed with a new dedicated core needle (Echotip ProCore® 20G, Cook, Inc., Bloomington, IN, U.S.A. or Acquire® 22 G or 25G, Boston Sci., Marlborough, MA). FNA samples were assessed by cytopathologists; FNB samples were sent for smear cytology, cell block and analyzed by surgical pathologists for the core tissue.

Results: FNA group with twenty-seven patients underwent 91 passes, average 3.36 passes. FNB group with 59 patients underwent 134 passes, average 2.27 passes. A diagnosis of malignancy was more likely with FNB than FNA (96.6% vs 71.0%). FNA and FNB had sensitivities, specificities, and accuracies for cancer (77.8% vs 96.5%, 100% vs 100%, and 96.6% vs 71.0%, respectively). The adverse event in both groups is the same and each group had one case of puncture site bleeding. FNB provided qualitative information not reported on FNA, such as degree of differentiation in malignancy, metastatic origin, and rate of

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P.055 proliferation in neuroendocrine tumors.

Conclusions: FNB using a newly designed dedicated core needle may reach more accurate diagnostic yield, less puncture pass, malignancy differentiation, the same adverse event and proliferation of neuroendocrine tumors.

經高頻超音波掃描測量之肝臟硬度而非脾 臟硬度可預測經消融治療後肝癌病人之預 後 LIVER STIFFNESS BUT NOT SPLEEN STIFFNESS MEASURED

BY ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY PREDICTED PROGNOSES OF HEPATOCELLULAR CARCINOMA AFTER RADIOFREQUENCY ABLATION 1

1

2

3

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1

鄭琮譯 李沛璋 陳炳憲 高偉育 霍德義 黃怡翔 2 1 1 1 侯明志 林漢傑 吳肇卿 蘇建維 1 臺北榮民總醫院胃腸肝膽科 2 臺北榮民總醫院內視鏡中心 3 臺北醫學大學附設醫院胃腸肝膽科

Background: The prognostic factors of patients who undergo radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is not fully elucidated.

Aims: We aimed to investigate the role of liver stiffness (LS) and spleen stiffness (SS) measured by acoustic radiation force impulse (ARFI) elastography in determining the prognoses of patients with HCC after RFA. Methods: We prospectively enrolled 173 patients with HCC who underwent ARFI elastography for measurement of LS and SS on the same day of RFA. Competing risk analyses of HCC recurrence-free survival (RFS), overall survival (OS), and hepatic decompensation were investigated.

Results: Patients with LS >1.5 m/s had significantly shorter OS and RFS than their counterparts. Anti-viral treatment (hazard ratio [HR]: 0.396, p=0.015) and LS >1.independently predicted poorer RFS. On the other hand, anti-viral treatment (HR: 0.315, p=0.010), creatinine >1.5 mg/dL (HR: 9.447, p=0.006), and SS >2.7 m/s (HR: 2.869, p=0.044) predicted a higher risk of hepatic decompensation.

Conclusions: LS but not SS measured by ARFI elastography predicted tumor recurrence and OS in RFAtreated HCC; whereas, SS predicted development of hepatic decompensation in these patients.

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P.056 UP-TO-8 Criteria 為巴塞隆那臨床肝癌期別 B 的病人，接收第一次經動脈灌流化學栓塞 治療之完全緩解的預測因子 UP-TO-8 CRITERIA IS ASSOCIATED WITH COMPLETE RESPONSE TO TRANSARTERIAL CHEMOEMBOLIZATION FOR BCLC STAGE B HEPATOCELLULAR CARCINOMA

highly associated with RFS. Conclusions: Within up-uo-8 criteria, a higher chance of CR can be expected by the first TACE in treatment-naïve BCLC B HCC patients. However, beyond up-to-7 criteria has poorer RFS after CR by the first TACE.

洪雅文 臺北榮民總醫院 Background: Transarterial chemoembolization (TACE) is performed as a standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma.

However, only a few patients achieve complete response (CR) after the first session of TACE. Even for those patients who achieve CR, significant portion of them encounter HCC recurrence in a short period of time.

Aims: This study is aimed to investigate the factors associated the CR by the first session of TACE in BCLC B HCC patients and the factors related to recurrence-free survival (RFS) after CR. Methods: A total of 560 treatment-naïve BCLC B HCC patients who were initially treated with TACE from 2007 to 2016 in Taipei General Veteran Hospital were enrolled.

Ten patients undergoing liver transplantation or curative operation after downstaging by the first TACE were excluded. The detailed tumor characteristics, liver function and demographic characteristics related to complete response after the first session of TACE and recurrencefree-survival were analyzed.

Results: Of the 560 BCLC B HCC patients, 56 patients achieved complete response to TACE. In multivariate analysis, age > 70 years-old (Odds ration[OR]= 2.246, P=0.006), tumor size > 6cm (OR= 0.234, P<0.001), alpha-fetoprotein level >100 ng/ml (OR=0.422, P=0.012) were independent predictors of complete remission after first TACE session. Interestingly, up-to-8 criteria was a prognostic factor associated with CR by the first session of TACE (OR= 0.315, P<0.001). During the median followup of 18.05 months, 50 patients encounter HCC recurrence even achieving CR by prior TACE. The median RFS was 8.92 months. In multivariate analysis, tumor number ≥3 (Hazard ratios[HR]= 2.731, P=0.008) and tumor size >6 cm (HR=5.084, P=0.002) were significantly related to recurrence free survival. Up-to-7 or up-to-8 criteria was

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P.057 單一巨型肝癌患者接受切除手術之預後 THE PROGNOSIS OF PATIENTS WITH SOLITARY HUGE HEPATOCELLULAR CARCINOMA AFTER SURGICAL RESECTION 1,2

2,3

1

1,2,4

1,2

4,5

蘇建維 周嘉揚 魏正一 黃怡翔 侯明志 吳肇卿 1 臺北榮民總醫院內科部胃腸肝膽科 2 陽明大學醫學院醫學系 3 臺北榮民總醫院外科部一般外科 4 陽明大學醫學院臨床醫學研究所 5 臺北榮民總醫院醫學研究部

Background: For patients with a solitary huge (>10 cm in size) hepatocellular carcinoma (HCC) and without vascular invasion, the long-term survival after surgical resection (SR) has not yet been well studied till now.

Aims: We aimed to analyze the prognostic factors of SR for patients with solitary huge HCC. Methods: We retrospectively enrolled 90 patients with treatment-naïve, solitary HCC (>10 cm), with wellpreserved liver function and without image proved macrovascular invasion who had received SR treatment between 2007- 2016. Factors in terms of overall survival (OS) and recurrence were analyzed by a Cox proportional hazards model.

Results: There were no mortality cases within 30-days after SR. 75 patients (83.3%) had reached R0 resection. After resection, by pathological examination, nine (10%) patients had macrovascular invasion, and 79 patients (87.8%) had microvascular invasion in their surgical specimen. After a median follow-up of 28 (interquartile range 12.7- 56.1) months, 41 patients had died. The 1-year, 2-year, 3-year, and 5-year cumulative OS rate were 78.1%, 67.5%, 58.3% and 44.7%, respectively. A multivariate analysis showed that independent prognostic factors to poorer OS included albumin-bilirubin (ALBI) grade 2 or 3 (hazard ratio HR: 4.317, 95% confidence interval CI: 2.023- 9.209, p< 0.001) and no R0 resection (HR: 6.495, 95% CI: 2.975- 14.180, p< 0.001). The median recurrence free survival (RFS) was 19.4 (interquartile range 13.1- 25.7) months. The cumulative 1-, 2-, 3-, and 5- year cumulative RFS rates were 65.3%, 49.4%, 41.5% and 38.1% respectively in R0 resection group. In the non-R0 resection group the 1- and 2- year cumulative RFS rates were 19.6% and 0%. Age> 65 years (HR: 2.004, 95% CI: 1.106- 3.636, p= 0.022), AFP level ≥125 ng/ml (HR: 1.772, 95% CI: 1.024- 3.067, p= 0.041), ALBI grade 2 or 3 (HR: 5.055, 95% CI: 2.687-

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9.511, p< 0.001) and no R0 resection (HR: 5.458, 95% CI: 2.644- 11.264, p< 0.001) were independent factors predicting poorer RFS by a multivariate analysis.

Conclusions: SR provided a good long-term OS and RFS for patients with solitary huge (≥10 cm) HCC. As such, SR is recommended as the therapeutic priority for these patients.

2020 消化系聯合學術演講年會

P.058 Pembrolizumab 合併 lenvatinib 在不可手術 切除的肝癌產生高腫瘤反應率 PEMBROLIZUMAB PLUS LENVATINIB PRODUCES HIGH TUMOR RESPONSE RATE IN UNRESECTABLE HEPATOCELLULAR CARCINOMA 1

1

1

1

1, 2

吳啟榮 李杰如 洪雅文 侯明志 黃怡翔 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學臨床醫學研究所

Background: Multiple targeted agents and immune checkpoint inhibitors (ICIs) are available for systemic therapy of hepatocellular carcinoma (HCC) in recent 2 years. In general, the tumor response rate is still not satisfactory by targeted or ICI monotherapy. Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICI to produce synergistic anti-tumor effects. The ongoing phase 1b Keynote-524 study shows promising data by combining Pembrolizumab with Lenvatinib for advanced HCC. Aims: To evaluate the treatment response and adverse events of combination therapy with Pembrolizumab plus Lenvatinib in real-world.

Methods: From Jul. 2019, patients who received Pembrolizumab plus Lenvatinib for unresectable HCC were prospectively enrolled in this study. The status of HCC was either in advanced HCC or failed by prior targeted or ICI monotherapy. The dosage of Pembrolizumab was 100mg every 3 weeks. The starting dose of Lenvatinib was 10mg per day. Patients who had received at least 2 cycles of Pembrolizumab were evaluated in this report. The tumor responses were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Results: Till the end of 2019, 16 patients had received at least 2 cycles of Pembrolizumab, and 12 had evaluable post-treatment images either by CT or MRI. There were 4 (25%) in BCLC B, and 12 (75%) in BCLC C. Of them, 11 (68.8%) were treated as the first-line systemic treatment, 3 as the second-line and 2 as the third line systemic treatment. Of the 12 cases with post-treatment image studies, 6 (50%) had partial response (PR), 4 (33.3%) were stable disease (SD), and 2 (16.7%) had progressive disease (PD) by RECIST v1.1. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.3%

and 83.3%, respectively. Marked serum AFP reduction was observed at week 3 in PR and SD patients (median reduction: -76.8% & -75.5%, respectively). The most common TRAEs in any grade were hypertension 12(75%), palmar-plantar syndrome 12(75%), fatigue 9(56.3%) and hypothyroidism 9(56.3%). The Grade 3/4 TRAEs were 2 (12.5%) with psoriasis-like skin reaction, 1 (6.3%) palmarplantar syndrome and 1 (6.3%) diarrhea.

Conclusions: Pembrolizumab plus Lenvatinib produces reliable high antitumor response with tolerable safety profiles. Such combination therapy is a promising strategy for unresectable HCC in the future.

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P.059 比較肝硬化及非肝硬化且具胃食道靜脈瘤 的肝癌患者接受外科手術後的存活 A COMPARISON OF PROGNOSIS BETWEEN CIRRHOSIS AND NONCIRRHOSIS PATIENTS WITH HEPATOCELLULAR CARCINOMA AND CONCOMITANT WITH ESOPHAGOGASTRIC VARICES 1

1,2

3

1,2

1,2

4,5

魏正一 蘇建維 周嘉揚 黃怡翔 侯明志 吳肇卿 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學院醫學系 3 臺北榮民總醫院外科部一般外科 4 臺北榮民總醫院醫學研究部 5 國立陽明大學醫學院臨床醫學所

Background: Esophagogastric varices (EGV) is poor prognostic marker of survival in patients with cirrhosis or hepatocellular carcinoma (HCC). However, the prevalence and characteristics of cirrhosis among hepatocellular carcinoma (HCC) patients with EGV and it effect on prognosis of these patients who underwent surgical resection (SR) has not been well investigated till now.

Aims: To compare the long-term prognosis between cirrhosis and non-cirrhosis for patients with HCC and with EGV who received SR. Methods: This single center, retrospective study enrolled 102 patients with treatment-naïve HCC and with EGV who underwent SR as the first-line treatment from 2003 to June, 2019. EGV was diagnosed by an esophagogastroduodenoscopy at the time of HCC diagnosis. Cirrhosis was defined over 5 for Ishak fibrosis stage after analyzed liver specimen. Prognostic factors were analyzed by the Cox proportional hazards model.

Results: A total of 70 patients was diagnosed with cirrhosis and the remaining 32 patients did not have cirrhosis. Compared to their counterparts, cirrhotic HCC patients had lower serum alkaline phosphate, gammaglutamyl transferase and creatinine level, smaller tumor size and poorer liver functional reservation presenting by longer prothrombin time, and lower platelet counts. After a median follow-up duration of 44.7 months, 54 patients died. The cumulative 5-year overall survival (OS) rate was 55.9% in cirrhotic HCC, and 44.0% in the non-cirrhotic patients, respectively (P =0.329). A multivariate analysis showed that patient with alpha fetoprotein (AFP) >20 ng/ml (hazard ratio HR 1.850, 95% confidence interval CI 1.044- 3.278, P =0.035), presence of macrovascular

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invasion by radiological report (HR 2.765, 95% CI 1.2556.095, P =0.012) and presence of high bleeding risk esophageal varices (HR 1.959, 95% CI 1.113- 3.449, P =0.020) were the independent risk factors predictive of poor OS for HCC patients with EGV. In this cohort, 77 patient developed tumor recurrence. The cumulative 5-year recurrence free survival (RFS) rate was 18.9% in cirrhotic HCC, and 21.9% in the non-cirrhotic patients, respectively (P =0.541). A multivariate analysis showed that patient with alpha fetoprotein (AFP) >20 ng/ml (hazard ratio HR 1.768, 95% confidence interval CI 1.132- 2.761, P =0.012), Serum total bilirubin level ≥1.0 mg/dl (HR 1.680, 95% CI 1.064- 2.653, P =0.026) and BCLC stage B&C (HR 2.090, 95% CI 1.264- 3.454, P =0.004) were the independent risk factors predictive of poor RFS for HCC patients with EGV. Conclusions: Not all HCC patients with EGV had an underlying liver cirrhosis. Liver cirrhosis with EGV is not absolutely contraindicated to HCC patients to underwent SR.

2020 消化系聯合學術演講年會

P.060

P.061

肝癌在病因、表徵、處置和預後評估工具上 演變 EVOLUTION OF ETIOLOGY, PRESENTATION, MANAGEMENT AND PROGNOSTIC TOOL IN HEPATOCELLULAR CARCINOMA

晚期肝細胞癌患者合併使用 Nivolumab 組 合治療的真實數據 REAL-WORLD DATA ON NIVOLUMAB COMBINATION TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

1,3

1,3

1,3,4

1,4

2,3,5

柯智傑 何樹仁 黃怡翔 侯明志 霍德義 1 臺北榮民總醫院 2 臺北榮民總醫院, 醫研部 3 國立陽明大學醫學院 4 國立陽明大學醫學院臨床醫學研究所 5 國立陽明大學醫學院藥學部

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death globally, but its current status is unclear.

Aims: To investigate the evolution of etiology, presentation, management and prognostic tool in HCC over the past 12 years.

Methods: Between 2004 and 2015, 3349 newly diagnosed HCC patients were consecutively enrolled and retrospectively analyzed. The comparison of survival was performed by the Kaplan-Meier method with log-rank test.

Homogeneity and corrected Akaike information criteria (AICc) were used to evaluate the prognostic accuracy for different staging systems.

Results: Hepatitis B and C virus infection in HCC were continuously declining over the three time periods (20042007, 2008-2011, 2012-2015; p<0.001). At diagnosis, single tumor detection rate increased to 73% (p<0.001), whereas vascular invasion gradually decreased to 20% in 2012-2015 (p<0.001). More patients (76%) had Child-Turcotte-Pugh class A in 2012-2015 (p<0.001). Early stage HCC, as defined in most staging systems, also gradually increased from 20042007 to 2012-2015 (p<0.001). The probability of patients receiving curative treatment increased from 2004-2007 to 2012-2015 (p<0.001). Long-term survival significantly increased for patients in 2012-2015 as compared with other two cohorts. The Cancer of Liver Italian Program (CLIP) and Taipei Integrated Scoring (TIS) system are two more accurate staging systems among all.

Conclusions: The clinical presentations of HCC have significantly changed over the past 12 years. Hepatitis B and C-associated HCC became less common, and more patients were diagnosed at an early cancer stage. Patient survival increased due to early cancer detection that results in increased probability to undergo curative therapies.

許菁惠 陳政國 亞洲大學附屬醫院 Background: Nivolmab, an anti-PD-1 antibody, has presented durable response and long-term survival in advanced hepatocellular carcinoma patients after Sorafenib treatment failure based on clinical trial of Check-Mate 040.

However, the potential synergistic effects when used the anti-PD-1 in combination with agents of other checkpoint molecules, systemic therapies, as well as locoregional therapies are also being explored in clinical practices.

Aims: The goal of this analysis is to evaluate the efficacy of Nivolumab for aHCC from Asia Universal Hospital (AUH) in real-world context.

Methods: Retrospectively, we examined the total 26 advanced aHCCpatients (disease confirmed by either radiologic definition and/or pathology) who were treated with two months or longer of Nivolumab, either Nivolumab alone or in combination with locoregional therapy and/or TKIs from July 2018 to Oct 2019.

Results: Result of 26 patients had variable liver disease at baseline with 58% of Child-Turcotte-Pugh (CTP) A, 38% of Child-Turcotte-Pugh (CTP) B, and 4% of Child-TurcottePugh C disease. 54% of patients received Nivolumab concurrent treatment with TKIs, 12% with Chemotherapy, and 39% combined with locoregional therapy (4% of TACE and 35% of radiotherapy). In this evaluation, the objective response rate (ORR) by investigating view was 27% from Child-Turcotte-Pugh (CTP) A patient groups, and DCR was 47%; for the Child-Turcotte-Pugh (CTP) B patient group, the objective response rate (ORR) was 28% and with disease control rate of 64% .

Conclusions: Correlations to the real-world practicing in Asia University Hospital (AUH), we have found the combination treatment, either combined with locoreginal therapy or TKIs or both, the responses were better than mono-immune treatment. And the side-effects and toxicity were manageable with close monitor. Combination maybe one of the encouraging strategy and in the future expectancy for aHCC treatment.

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P.062 Albumin-bilirubin (ALBI) 分級可以區分亞 洲慢性 B 型肝炎肝硬化患者接受貝樂克治 療後之肝癌發生與總死亡風險 RISK STRATIFICATION OF HEPATOCELLULAR CARCINOMA OCCURRENCE AND OVERALL MORTALITY BY ALBUMIN-BILIRUBIN (ALBI) GRADE IN ASIAN CIRRHOTIC PATIENTS WITH CHRONIC HEPATITIS B ON ENTECAVIR THERAPY 1

2

1

2

2

1

王鴻偉 陳建宏 賴學洲 胡琮輝 王景弘 彭成元 1 中國醫藥大學附設醫院消化醫學中心 2 高雄長庚紀念醫院內科部胃腸肝膽科系

Background: Noninvasive scores including albuminbilirubin (ALBI), platelet-albumin-bilirubin (PALBI), and model for end-stage liver disease (MELD) score have been used to assess the severity of liver dysfunction and predict the liver-related outcome.

Aims: We aimed to investigate the predictive performance for hepatocellular carcinoma (HCC) and overall mortality by baseline noninvasive score in patients with chronic hepatitis B (CHB) who received nucleos(t)ide analogue (NA) therapy.

Methods: A total of 1325 prior NA-naïve CHB patients receiving entecavir therapy were enrolled from January 2007 to August 2012. Baseline clinical characteristics and laboratory data were collected. Risk factors and noninvasive scores were analyzed by univariate and multivariate Cox regression analyses and compared for their predictive performance of HCC and overall mortality by receiver operating characteristic (ROC) curve analysis.

Results: A total of 105 patients developed HCC and 19 patients died. In non-cirrhotic patients, ALBI, PALBI, and MELD scores were not predictive of HCC or overall mortality. In cirrhotic patients, age (hazard ratio [HR]: 1.030; 95% confidence interval [CI]: 1.011–1.050, P = 0.002), diabetes mellitus (HR: 1.681; 95% CI: 1.020–2.772, P = 0.042) and ALBI grade (Grade 3, HR: 3.845; 95% CI: 1.876–7.880, P < 0.0001 and Grade 1, as reference) were independent predictors for HCC, and platelet (HR: 0.977; 95% CI: 0.963–0.991, P = 0.001) and ALBI grade (Grade 3, HR: 24.81; 95% CI: 4.278–143.9, P < 0.001 and Grade 1 as reference) were independent predictors for overall mortality by multivariate Cox’s regression analysis. PLABI and MELD grades were not independent predictors for HCC or overall mortality. The predictive performance of ALBI

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for HCC was significantly higher than those of the other indices for total patients (AUROCs: ALBI, 0.632; PALBI, 0.513; and MELD, 0.560) but was only marginally higher for cirrhotic patients (AUROCs: ALBI, 0.626; PALBI, 0.593; and MELD, 0.535). ALBI exhibited significantly higher predictive performance for overall mortality than did PALBI and MELD for total and cirrhotic patients.

Conclusions: The baseline ALBI grade was an independent predictor and could stratify HCC risk and overall mortality in cirrhotic patients with CHB undergoing long-term entecavir therapy.

2020 消化系聯合學術演講年會

P.063 比較手術合併輔助性肝動脈化學藥物灌注 治療和單純手術對於手術可切除肝癌的療 效 - 系統性文獻回顧與統合分析 COMPARATIVE EFFICACY OF RESECTION WITH ADJUVANT HEPATIC ARTERIAL INFUSION CHEMOTHERAPY VERSUS RESECTION ALONE FOR RESECTABLE HEPATOCELLULAR CARCINOMA-A SYSTEMATIC REVIEW AND METAANALYSIS 1,2

alone, respectively. The meta-analysis demonstrated that the overall survival (HR: 0.53, 95% CI: 0.36-0.77, P < 0.01) and disease-free survival (HR: 0.53, 95% CI: 0.39-0.72, P < 0.01) were better in the resection with adjuvant HAIC group than these in the resection alone group.

Conclusions: Adjuvant HAIC is effective for the patients with resectable HCC after curative surgery, especially the patients with high risk of recurrence.

1,3

廖思涵 高嘉宏 1 臺大醫院內科部胃腸肝膽科 2 臺大癌醫中心醫院 3 臺灣大學醫學院臨床醫學研究所 Background: Hepatocellular carcinoma (HCC) is an important global health issue. HCC is the fifth most common solid organ tumor and the second leading cause of cancer-related death worldwide. The primary treatment for HCC is surgical resection. However, the recurrence rate is up to 70% in 5 years after resection and recurrence leads to lowering survival. The risk factors associated with recurrence include surgical margin less than 1 mm, residual tumor satellites in the liver, microscopic intravascular tumor thrombi and lack of capsule. The role of adjuvant therapy for resectable HCC with high risk of recurrence is still controversial.

Aims: The aim of this study is to investigate comparative efficacy of resection wih adjuvant hepatic arterial infusion chemotherapy (HAIC) versus resection alone for resectable HCC. Methods: Online search from PubMed, Medline, Embase, Web of science and Cochrane library for studies to compare resetion with adjvant HAIC with resection alone for the patients with resectable HCCs during January, 1990 to October, 2019 was performed. Primary outcome was overall survival. Secondary outcome was diseasefree survival. Quality assessment of included studies was evaluated using the Cochrane Collaboration’s Tools for randomized clinical trial and the Newcastle-Ottawa scale for observational studies. Hazard ratio (HR) with 95% confidence interval (CI) were calculated from pooled data.

Results: The search strategy identified two randomized clinical trials and ten cohort studies fitting selection criteria.

A total of 498 and 888 patients with resectable HCCs underwent resection with adjuvant HAIC and resection

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P.064 非酒精性脂肪肝病與 B 型肝炎相關肝癌病 人之臨床特性及生存預後差異 DIFFERENCES OF CLINICAL CHARACTERISTICS AND SURVIVAL OUTCOMES IN NONALCOHOLIC FATTY LIVER DISEASE AND HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA PATIENTS 1

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林柏任 林聰蓉 林志陵 廖麗瑛 張廷安 丁金聰 1 陳冠仰 1 臺北市立聯合醫院仁愛院區消化內科 2 臺北市立聯合醫院仁愛院區病理科 3 臺北市立聯合醫院仁愛院區消化外科

Background: The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) 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, cirrhosis, and eventually HCC in recent years.

Aims: The aim of our study is to investigate and compare the clinical features of HCC in NAFLD and HBV patients, including age, gender, cirrhosis, liver function tests, largest tumor size and cancer stage at the time of diagnosis. The survival outcome was also analyzed in the two groups.

Methods: HCC patients in NAFLD were recruited from the data base of Cancer Registries in Taipei City Hospital, RenAi Branch, from 2011 to 2017; and consecutively from the HCC multidisciplinary conference between January, 2018 and December, 2019. All HBV-related HCC patients 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 antiHBs or negative anti-HBc), non-viral hepatitis C (negative anti-HCV), nonalcoholic (alcohol consumption less than 30 g/day) liver disease and if present or past histological or ultrasonographic evidences of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis.

Results: NAFLD-related HCC patients were significantly older (70.0 ± 12.2 years old versus 63.8 ± 10.9 years old, p = 0.013) and more over-weighted (Body mass index (BMI): 27.1 ± 4.7 kg/m 2 versus 24.7 ± 5.2 kg/m 2, p = 0.036) than HBV-related. Only 34.8% (8/23) of NAFLD and 70.5% (110/156) of HBV-related HCC patients were cirrhotic. (p < 0.001). Child-Pugh classification A was in

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95.7% (22/23) of NAFLD and in 78.2% (122/156) of HBVrelated HCC patients. (p = 0.049). The bilirubin levels were significantly higher in HBV than in NAFLD patients (2.4 ± 4.5 mg/dl versus 0.9 ± 0.7 mg/dl, p = 0.001). There were no significant differences in gender, tobacco use and international normalized ratio between the two groups.

The levels of alpha-fetoprotein were significantly higher in NAFLD than in HBV-related HCC patients (1703.4 ± 7577.5 ng/ml versus 19.3 ± 36.4 ng/ml, p = 0.001). Tumor characteristics, including BCLC stage and size of largest tumor, were not significantly different between the two groups. After multivariate analysis, age (Hazard ratio: 1.092, 95% CI = 1.028 - 1.160, p = 0.004), BMI (Hazard ratio: 1.162, 95% CI = 1.017 - 1.328, p = 0.027) and cirrhosis (Hazard ratio: 0.097, 95% CI = 0.024 - 0.400, p = 0.001) were still significantly different factors between NAFLD and HBV-related HCC patients. Survival rates at 1 year and 3 years were 91.3% and 82.6% in NAFLD, and 67.9% and 64.7% in HBV-related HCC patients. The differences were not statistically significant by Log Rank test (p = 0.101).

Conclusions: In conclusion, our study showed NAFLDrelated HCC patients were older and more over-weighted than HBV-related. In addition, more NAFLD-related HCC patients were non-cirrhotic than HBV-related. The other factors, including HCC stage, largest tumor size, and survival outcome, were not significantly different between the two groups.

2020 消化系聯合學術演講年會

P.065 接受肝動脈化學栓塞治療之肝癌病患在不同 BCLC B 預測模式下其腫瘤治療反應與慢性 肝功能代償不全的比較 COMPARISON OF TUMOR RESPONSE AND CHRONIC LIVER DECOMPENSATION AMONG DIFFERENT BCLC B PROGNOSTIC SCORING SYSTEMS TO TRANSARTERIAL CHEMOEMBOLIZATION IN HEPATOCELLULAR CARCINOMA 1

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grade migration. In multivariate analysis, AST >45 IU/L, total bilirubin >1.2 mg/dl, Child-Pugh B, and ALBI II or III were factors associated with post-TACE chronic liver decompensation.

Conclusions: Not all BCLC B patients are eligible f o r TA C E . T h e n e t b e n e f i t o f TA C E s h o u l d b e balanced between tumor response and the risk of liver decompensation.

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齊振達 李懿宬 李潤川 蘇建維 侯明志 趙毅 1,4 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 臺北榮民總醫院放射線部 3 臺北榮民總醫院癌症中心 4 國立陽明大學臨床醫學研究所

Background: Transarterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC). But heterogeneity in tumor and clinical characters result in diverse clinical outcome to TACE therapy.

Aims: The study aimed to assess the utility of various tumor numbers plus tumor size scores in predicting tumor response and the risk of chronic liver decompensation after TACE in HCC. 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 mRECIST and the incidence of chronic liver decompensation among different prognostic systems were evaluated. Factors association with ORR and chronic liver decompensation were analyzed.

Results: The ORRs were 55.4% and 37.7% in patients within or beyond up-to-6 criteria (p = 0.004); 49.1% and 36.6% in patients within or beyond up-to-7 criteria (p = 0.009); 47.7% and 20.6% in patients within or beyond upto-11 criteria (p < 0.001); 45.8% and 19.6% in patients within or beyond up-to-12 criteria, respectively (p < 0.001). Age, AST, Albumin, INR, Child-Pugh class, and the four tumor numbers plus size systems were factors associated with the ORR. In general, the risk of chronic liver decompensation after TACE were 7.5%. The four tumor numbers plus tumor size scores could not predict the risk of liver decompensation, but associated with ALBI

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P.066 合併 Sorafenib 與局部治療在中期肝細胞癌 病患之療效 EFFICACY OF COMBINING SORAFENIB AND LOCAL-REGIONAL TREATMENT IN PATIENTS WITH INTERMEDIATESTAGE HEPATOCELLULAR CARCINOMA 1

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洪子鈞 郭欣瑜 吳毅晉 張定宗 林毅志 蔡宏名 1 陳炯瑜 1 國立成功大學醫學院附設醫院內科部 2 國立成功大學醫學院附設醫院臨床醫學研究所 3 國立成功大學醫學院附設醫院外科部 4 國立成功大學醫學院附設醫院放射診斷部

Background: Sorafenib treatment is suggested for patients with intermediate-stage hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE).

Aims: This study aimed to study if combining local regional treatment with sorafenib adds benefit to patients who had tumor progression after three sessions of TACE within 12 months.

Methods: We retrospectively analyzed the treatment outcomes of sorafenib alone and combined treatment of sorafenib and local-regional therapies in patients with intermediate-stage HCC patients. The overall response rate (ORR) was assessed using the modified Response Evaluation Criteria in Solid Tumors 1.1 criteria. The survival time, time to liver dysfunction (TTLD), and extrahepatic metastases were analyzed by using multivariate regression analysis.

Results: Forty-nine patients were enrolled; 28 patients treated with sorafenib alone, whereas 21 patients received TACE or radiofrequency ablation (RFA) in addition to sorafenib. The ORR was significantly higher in the sorafenib-combination group than the sorafenib-alone group (33.6% vs. 11.3%; p = 0.016). The PFS was also significantly longer in the patients of sorafenib-combination group than alone group (median 4.8 vs. 2.9 months, HR, 0.61; 95% CI, 0.39-0.94; p < 0.05). The risk of extrahepatic metastases was significantly lower in the sorafenibcombination group (HR, 0.07; 95% CI, 0.01-0.37). The TTLD and incidence of adverse events were comparable between sorafenib-combination and sorafenib-alone groups (HR, 0.90; 95% CI, 0.42-1.90; p > 0.05).

Conclusions: Loco-regional therapies may be still able to exert additional survival benefit to patients taking sorafenib for TACE-refractory intermediate-stage HCC showing

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a better PFS and lower risk of extrahepatic metastases without causing significant liver dysfunction. Further investigations to identify patients who will be more likely to benefit from the combination of sorafenib with localregional therapies are needed.

2020 消化系聯合學術演講年會

P.067

P.068

使 用 Metformin 對 BCLC 0/A 糖 尿 病 肝 癌 病人接受根除性切除手術後的預後無明顯 優勢 NO SIGNIFICANT ADVANTAGE IN OUTCOMES OF METFORMIN USAGE IN BCLC0/A HEPATOCELLULAR CARCINOMA PATIENTS WITH DIABETES MELLITUS AFTER CURATIVE RESECTION

在肝癌病人中以 PIVKA II 作為經動脈化學 栓塞術治療成效之預測 USING PIVKA-II TO PREDICT THERAPEUTIC RESPONSES OF TRANSARTERIAL CHEMOEMBOLIZATION IN PATIENTS OF HEPATOCELLULAR CARCINOMA

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卓韋儒 蔡明釗 黃寳源 陳永年 蔡孟耘 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 長庚醫療財團法人高雄長庚紀念醫院內分泌暨新陳代 2 謝科 3 長庚醫療財團法人高雄長庚紀念醫院內科部 Background: Metformin is proposed to have chemopreventive effect of various cancers currently.

However, it is still controversial and unclear about the anticancer effect of metformin for hepatocellular carcinoma (HCC) after resection.

Aims: Our study aimed to evaluate the effects of metformin on the clinical outcomes of BCLC 0-A HCC patients with DM after curative resection.

Methods: We enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with DM from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis.

Results: During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.034), low albumin level (p = 0.032), liver cirrhosis (p < 0.001), tumor number (p <0.001), tumor size (p =0.001), histology stage (p =0.001), vascular invasion (p <0.001) and hepatitis C (p =0.031) were independent predictors for RFS. In patients with DM, HbA1C>9 (p = 0.002), Child-Pugh grade B vs. A (p = 0.018) and vascular invasion (p = 0.022) were independent risk factors for HCC recurrence. The impact of metformin, sulfonylurea and insulin revealed no statistically significant in univariate analysis. Furthermore, insulin use (p =0.002), low albumin level (p =0.003), vascular invasion (p =0.027) in multivariate analysis revealed increase risk for death in patients with DM after curative hepatectomy.

Conclusions: In BCLC 0/A HCC patients with DM after curative resection, Metformin dose not have significant effects in HCC recurrence and overall survival. However, adequate DM control can reduce the recurrence of HCC.

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王崧穎 蘇東弘 陳邦斌 劉俊人 劉振驊 楊宏志 1,2 1,2,4 1,2,4,6 1,2,4,5 曾岱宗 陳培哲 陳定信 高嘉宏 1 臺灣大學附設醫院內科部肝膽腸胃科 2 臺灣大學附設醫院肝炎研究中心 3 臺灣大學附設醫院內科部影像醫學科 4 臺灣大學臨床醫學研究所 5 臺灣大學附設醫院醫學研究部 6 中央研究院基因體研究中心

Background: Protein induced by Vitamin K absence-II (PIVKA-II) complements alpha-fetoprotein (AFP) for the diagnosis, monitoring the treatment responses, and may predict the survival of hepatocellular carcinoma (HCC).

Transarterial chemoembolization (TACE) is a standard treatment in intermediate stage of HCC; however, the predictors for tumor responses after TACE are lacking.

Aims: To investigate the serial changes and predictive role of PIVKA-II for treatment responses in HCC patients receiving TACE. Methods: We conducted a prospective study in patients with HCC undergoing TACE at National Taiwan University Hospital consecutively. Serial serum samples were collected before, at 1st day, 7th day, and 1 months after TACE and stored in -80C refrigerators. PIVKAII were measured by Abbott Architect PIVKA-II assay.

A radiologists was consulted for image review before and after TACE, including the BCLC staging, tumor numbers, maximum size, distribution, morphology, arterial enhancement, portal hypertension, portal vein thrombosis, and etc.

Results: From 2012 to 2014, a total of 48 patients were included in this study. The median age was 64and 73% were male, and they were followed for a median of 17 months. Eighty-five percent of patients had Child-pugh A liver function. The BCLC stage of HCC was A (25%), B (58%) and C (17%) and the median log10(PIVKA-II) was 2.2 before TACE. Eight patients (17%) had a complete responses to the index TACE (TACE-complete group).

PIVKA-II positively correlated with AFP, maximum tumor size, and portal vein thrombosis. The serial PIVKA-

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P.069 II levels in the TACE-complete group were significantly lowered than the TACE-incomplete group at all time points. A low baseline log10PIVKA-II level help to predict the complete tumor response of TACE (Odds ratio: 0.05, 95% confidence interval [CI]: 0.004-0.745, P=0.03), While infiltrative morphology predicts the overall survival (hazard ratio: 3.79, 95% CI: 1.41-10.2, P=0.008).

Conclusions: Low baseline PIVKA-II level in HCC patient help to predict the treatment response of TACE.

肝彈性度和胰島素抗性預測早期肝癌治癒 性切除後的復發 LIVER STIFFNESS AND INSULIN RESISTANCE IN PREDICTING LATE RECURRENCE FOR PATIENTS WITH EARLY-STAGE HEPATOMA AFTER CURATIVE RESECTION 1

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王景弘 李韋鋒 楊志權 劉約維 盧勝男 王植熙 1 長庚醫療財團法人高雄長庚紀念醫院內科部 2 長庚醫療財團法人高雄長庚紀念醫院外科部

Background: Curative resection is recommended for patient with early-stage hepatocellular carcinoma (HCC), however, the prognosis is limited by high recurrence rate.

Aims: The study was to investigate liver stiffness (LS) in prediction of HCC recurrence for patients with early-stage HCC who had undergone resection.

Methods: Consecutive patients with suspicion of HCC who had undergone curative resection were prospectively enrolled. Transient elastography was performed to determine LS pre-operatively. The demographics, clinical characteristics and histological findings were recorded. All patients were followed up regularly until recurrence, death or last visit. HCC recurrence after one-year post-curative resection was defined late recurrence.

Results: Between August 2012 and February 2016, ninetyfour patients with BCLC early-stage HCC were enrolled.

LS correlated with fibrosis stage (r=0.666). In a median follow-up of 3.2 years, forty patients developed recurrences including 22 late recurrences. The 5-year cumulative recurrence rate was 44.2%. LS as the independent factor associated with recurrence (HR: 1.03, p=0.011), LS >8.5kPa (HR: 2.72, p=0.039) and homeostatic model assessment for insulin resistance index (HOMA) (HR: 1.24, p=0.003) were both risk factors of late recurrence in multivariate analysis. LS performance was 0.641 in the prediction of recurrence. Patients with LS >8.5kPa had higher 5-year cumulative recurrence rate (59.8% vs 25.1%, p=0.007). There was higher late recurrence rate for those patients with both LS>8.5kPa and HOMA>2.3 (p=0.003).

Conclusions: For patients with early-stage HCC who had undergone curative resection, LS and HOMA were independently associated with late recurrence. Patients with LS>8.5kPa and HOMA>2.3 had the highest late recurrence rate.

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P.070

P.071

在 BCLC stage B 且多顆肝癌病人治療選擇： 肝動脈化療 VS 肝動脈栓塞 HEPATIC ARTERIAL INFUSION CHEMOTHERAPY VERSUS TANSARTERIAL EMBOLIZATION FOR BCLC STAGE B MULTINODULAR HEPATOCELLULAR CARCINOMA

長片段非編碼 RNA CRNDE 在肝細胞癌的 研究 UP-REGULATION OF LNCRNA CRNDE IN HUMAN HEPATOCELLULAR CARCINOMA

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翁維駿 蔡維倫 孫煒智 陳文誌 鄭錦翔 1 高雄榮民總醫院 2 國立陽明大學醫學系 3 國軍高雄總醫院

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Background: BCLC stage B hepatocellular carcinoma (HCC) corresponds to a highly heterogeneous population.

Although TACE/TAE is recommended as the standard treatment for BCLC stage B HCC, it has been shown to have poor effects for multinodular HCCs. Hepatic arterial infusion chemotherapy (HAIC) is beneficial for BCLC-C and huge HCC (1), but its effects for BCLC stage B multinodular HCC remains unclear.

Aims: This retrospective study aims to compare the efficacy of HAIC and TAE for BCLC stage B multinodular HCC. Methods: From 2005 to 2017, we retrospectively review the data of consecutive patients with BCLC stage B multinodular HCC who received HAIC or TAE. Baseline characteristics, treatment response, and overall survival were compared.

Results: A total of 184 patients, including 67 in HAIC group and 117 in TAE group, were enrolled in this study.

The baseline characteristics were comparable except younger age (62.4 versus 69.3 y/o, p=0.001), higher platelet count (237.1/x103cumm versus 151.9/ x103cumm, p=0.001), higher AFP level ( 42025ng/ml versus 5068ng/ ml, p=0.03), and larger tumor size (10.9cm versus 6.9cm, p=0.001) were noted in HAIC group compared with TAE group. The overall treatment response rates were 26.9% (CR: 10.4%, PR: 16.5%) in HAIC group and 26.5% (CR: 12.8%, PR: 13.7%) in TAE group (p=0.54). The overall median survival were 17 months in HAIC group and 18 months in TAE group (p=0.54). The 1-, 3-, 5-year survival rates were 54.6%, 24.4%, 14.4% in HAIC group and 61.2%, 32.4%, 17.0% in TAE group (p=0.29).

Conclusions: HAIC had similar effects as TAE for BCLC stage B multinodular HCC.

徐祖岳 林煊淮 黃信閎 施宇隆 張維國 謝財源 三軍總醫院內科部胃腸科 Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in Taiwan. Malignant transformation of hepatocytes is believed to be associated with the progressive accumulation of many genetic and epigenetic alterations regardless of aetiological factors, which results in the deregulation of oncogenes and tumorsuppressor genes. Increasing evidence shows that the deregulation of non-coding RNA expression is associated with HCC. Long non-coding RNAs (lncRNAs) have been reported to play an important role in regulating gene expression. Although the molecular mechanisms through which lincRNAs function are not fully clarified, diverse regulatory mechanisms including epigenetic silencing, lncRNA-microRNA interaction, lncRNA-protein interaction, and splicing regulation have been reported for several well-characterized lncRNAs. LncRNA CRNDE is considered to be involved in human cancers.

Aims: To investigate the role of lncRNA CRNDE in human hepatocellular carcinoma.

Methods: Quantitative real-time PCR and cell proliferation assay were used in this study.

Results: We showed that lncRNA CRNDE expression was significantly up-regulated in HCC tissues compared to adjacent non-tumor liver tissues. We also showed that lncRNA CRNDE overexpression promoted cell proliferation in HCC cells. Furthermore, we found that exosomal lncRNA CRNDE is higher in patients with HCC than those with chronic hepatitis.

Conclusions: This study indicated that the up-regulation of lncRNA CRNDE expression involved in HCC development. Furthermore, exosomal lncRNA CRNDE may contribute to the development of noninvasive biomarkers of HCC diagnosis.

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2020 消化系聯合學術演講年會

P.072

P.073

遵循修改過的巴塞隆納肝癌分期的治療建 議：一個亞洲醫學中心報告 ADHERENCE TO THE MODIFIED BARCELONA CLINIC LIVER CANCER GUIDELINE IN FIELD-PRACTICE: RESULTS OF AN ASIA ACADEMIC MEDICAL CENTER

肝癌合併食道靜脈曲張病患接受手術或熱 射頻腫瘤消融術具有相同之術後食道靜脈 曲張出血率 SIMILAR POST-PROCEDURE VARICEAL BLEEDING RATE BETWEEN PATIENTS RECEIVE SURGICAL RESECTION AND RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA TREATMENT

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葉文碩 胡琮輝 鄭汝汾 王景弘 林志哲 顏毅豪 1 高雄長庚紀念醫院胃腸肝膽科系 2 高雄長庚紀念醫院放射診斷科系 3 高雄長庚紀念醫院一般外科系

Background: Previous studies reported that non-adherence to original Barcelona Clinic Liver Cancer (BCLC) guideline were common in field-practice.

Aims: We aim to evaluate the adherence to the modified BCLC guideline in an academic medical center in Taiwan, where all treatment modalities were available and reimbursed by Taiwan’s National Health Insurance Administration. Further, to prospective validate the prognostic ability of the modified BCLC staging system, which is not reported previously.

Methods: 2055 consecutive patients with de-novo HCC and managed at Kaohsiung Chang Gung Memorial hospital enrolled from January 2011 to December 2017.

After excluded patients with decompensated cirrhosis and received treatment other than liver transplant or best supportive care (n=254), 1801 patients enrolled in this study.

All patients received treatment through a multidisciplinary team (MDT) decision and were followed until death or end of follow-up.

Results: Adherent treatment to the modified BCLC recommendations was in 259 (85.8%) BCLC 0 patients, 533 (77.5%) BCLC A, and 138 (40.9%) BCLC B, 93 (26.0%) BCLC C, 83(71.6%) BCLC D. The median OS were 77.9, 67.8, 39.9, 11.0, and 3.9 months in modified BCLC stage 0, A, B, C and D, respectively (log rank test P<0.001).

Conclusions: non-adherence to the modified BCLC guidelines are common in BCLC stage B and C in an Asia academic medical center. The prognostic ability of modified BCLC staging system has been prospectively validated.

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呂學聖 楊宗傑 張重昱 黃怡翔 侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 陽明大學醫學系 3 臺北榮民總醫院內視鏡診斷暨治療中心

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Background: Esophageal variceal bleeding carried a higher re-bleeding rate and dismal prognosis in patients with hepatocellular carcinoma (HCC) than cirrhotic patients. However, the rates of esophageal variceal bleeding after surgical resection or radiofrequency ablation (RFA) for HCC were rarely been assessed.

Aims: The aim of this study is to evaluate the rate of esophageal variceal bleeding after surgical resection or radiofrequency ablation for HCC. Methods: From Janunary 2008 to May 2014, the study retrospectively enrolled 111 HCC patients who received surgical resection or RFA for HCC with treatment naïve esophageal varices (EV) and Barcelona Clinic Liver Cancer (BCLC) stage 0 or A. The cumulative six weeks variceal bleeding after surgical resection or RFA was the primary end-point.

Results: In the study cohort, 26 patients in surgical resection group and 85 patients in RFA group. Most of the patients were male (71.2%) and hepatitis B related HCC (43.2%). Patients in surgical resection group was younger than RFA group (65.7 vs. 72.3, p=0.012). There were no difference in HCC etiology, BCLC stages, sex, EV size between two groups. The median follow up time was 47.7 (19.6-63.1) months. The six weeks cumulative postprocedure esophageal variceal bleeding rate was 7.7% in surgical resection group and 3.5% in RFA group (p=0.377).

The overall cumulative esophageal variceal bleeding rate was 15.4% in surgical resection group and 16.5% in RFA group (p=0.845).

Conclusions: The post-procedure six weeks and overall esophageal variceal bleeding rates were similar between patients receive surgical resection and RFA for HCC treatment.

2020 消化系聯合學術演講年會

P.074 探討免疫療法 anti-PD1 於長期服用免疫抑 制劑的肝癌小鼠治療效果 THERAPEUTIC EFFECTS OF ANTI-PD1 IMMUNOTHERAPY ON ORTHOTOPIC HCC MICE WITH LONG-TERM ADMINISTRATION OF IMMUNOSUPPRESSANTS 1

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徐玉真 蘇建文 周慧琪 吳孟娟 李宣書 許秉寧 4 5 1,2 吳耀銘 陳健弘 許金川 1 財團法人肝病防治學術基金會 2 臺灣大學醫學院附設醫院內科 3 臺灣大學醫學院免疫學研究所 4 臺灣大學醫學院附設醫院外科 5 臺灣大學醫學院附設醫院雲林分院內科

showed significant anti-tumor effectsin both ectopic and orthotopic models of HCC by reducing the tumor size 90.84% and 70.95%, respectively.

Conclusions: Anti-PD-1 immunotherapy showed a significant reduction in tumor burden in our liver cancer mouse models who have taken immunosuppressants continuously. This model is also suitable for futher investigation of the immune response mechanisms and generating de novo immunotherapy approaches against HCC.

Background: Immunotherapies have been extensively investigated as alternative options for the treatment of hepatocellular carcinoma (HCC). However, the underlying mechanisms of immunotherapy in HCC remain unclear, and it is difficult to predict the treatment response and prognosis of patients after immunotherapy. Moreover, immunotherapy application has been restricted and concerned in the treatment of those HCC patients who are continuously under immunosuppressants, such as liver transplant recipients.

Aims: To explore mechanisms of action of antiPD1 therapy against HCC and evaluate the efficacy and responsiveness of anti-PD1 therapy under immunosuppressant treatment.

Methods: Immune-competent orthotopic HCC mouse models were used in C57BL/6J and BALB/c mice, the most widely used inbred strains, by implanting the syngeneic HCC cells into the subcapsular space of the liver. The efficacy of anti-PD1 therapy was evaluated by comparing tumor size and cellular components of the immune system with control groups after repeated administration (5 doses) of anti-PD1.

Results: Anti-PD-1 therapy showed significant antitumor effects by reducing the tumor sizes 69.33% and 67.03% in the C57BL/6J and BALB/c mouse models, respectively. Tumor-infiltrating CD8+ T cells, CD4+ T cells and NK cells were increased as early as 3 days after two doses of anti-PD-1 treatment. Furthermore, the number of tumor-infiltrating CD8+ T cells, but not CD4+ T cells, was significantly negatively correlated with tumor size. Following long term oral administration of immunosuppressant (tacrolimus), anti-PD-1 therapy still

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P.075 無法切除的肝臟惡性腫瘤患者的 SorafenibRegorafenib 接續治療 - 在醫學中心的經驗 SORAFENIB-REGORAFENIB SEQUENTIAL THERAPY IN PATIENTS WITH UNRESECTABLE HCCEXPERIENCE AT A MEDICAL CENTER 1

1, 2, 3

1, 2, 3

1, 2, 3

吳柏叡 張經緯 王蒼恩 蔡宗憲 1, 2, 3 王鴻源 1 馬偕紀念醫院內科部肝膽腸胃科 2 馬偕醫護管理專科學校 3 馬偕醫學院

1, 2, 3

陳銘仁

Background: Hepatocellular carcinoma (HCC) remains to be the leading causes of cancer-related death in Taiwan.

Sorafenib is the first-line systemic treatment for advanced HCC. The pivotal RESORCE trial showed that regorafenib was effective as second-line therapy for patients with advanced HCC who progressed on first-line sorafenib.

Real-world data are needed to assess clinical outcomes in the setting of daily practice in Taiwan.

Aims: We present real-world experience with sorafenibregorafenib sequential therapy in HCC. Methods: From Jan 2017 to Nov 2019 at MacKay Memorial Hospital, we retrospectively reviewed the medical records of HCC patients who had received sorafenib-regorafenib sequential therapy. Response evaluation was done based on mRECIST every two to four months after treatment.

Results: 16 patients had received sequential treatment with sorafenib followed by regorafenib between Jan 2017 and Nov 2019. A total of 11 patients were enrolled for analysis. The mean age was 54.5±10.8 years (range: 3271 years) and 90.1% were male patients. The proportion of patients positive for HCV Ab and HBsAg were 9.1 % and 80.8 %, respectively. Patients (100%) were ECOG performance status 0 or 1 and patients with Child-Pugh A was 8 (72.7%), Child-Pugh B was 3 (27.3%). The ratio of BCLC stage B and C were 36.4 % and 63.6 %, respectively. With mean follow-up duration of 4.73±2.08 months (range, 2-9). Neither complete response nor partial response was observed in these patients. 4 patients reached stable disease. The disease control rate (DCR) was 36.4 %. 8 patients (72.7%) received regorafenib in combination with other systemic or local regional treatment. Compared with regorafenib alone, the combination treatment of the regorafenib did not improve overall survival (p>0.05).

Conclusions: Compared to the clinical trial study of

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regorafenib, our real-world data showed lesser DCR (Disease control rate). More advanced disease status, liver dysfunction and short follow-up duration with a small sample size might explain it. Whether regorafenib in combination with multidisciplinary treatment have survival benefits for patients with HCC, proper prospective studies dedicated to this subgroup should be planned.

2020 消化系聯合學術演講年會

P.076

P.077

肝動脈灌注化療對於低血管性肝癌之療效 THE EFFICACY OF HEPATIC ARTERY INFUSION CHEMOTHERAPY FOR HYPOVASCULAR HEPATOCELLULAR CARCINOMA

改良肝動脈灌注化療對晚期肝細胞癌的影 響 EFFECT OF MODIFIED HEPATIC ARTERIAL INFUSION CHEMOTHERAPY (HAIC) ON ADVANCED HEPATOCELLULAR CARCINOMA (HCC)

1

1,2

1,2

1,2

1,2

1,2

孫煒智 蔡維倫 梁慧隆 陳文誌 余憲忠 鄭錦翔 1 高雄榮民總醫院內科部胃腸肝膽科 2 國立陽明大學

Background: Hypovascular hepatocellular carcinoma (HCC) is not unusual in clinical practice and is a challenge for hepatologists. Some studies reported the presence of hypovascular HCC to be a negative predictor in HCC patients receiving TACE/TAE which are usually not recommended for the treatment of hypovascular HCC. However, the efficacy of hepatic artery infusion chemotherapy (HAIC) for hypovascular hepatocellular carcinoma remains unclear.

Aims: This retrospective study aims to evaluate the efficacy of HAIC in patients with or without hypovascular HCC. Methods: From 2005 to 2017, HCC patients who received initial HAIC were retrospectively analyzed. Hypovascular HCCs were detected by dynamic computed tomography or magnetic resonance imaging before starting HAIC. Baseline data, treatment response and overall survival were compared between patients with and without hypovascular HCC. Results: A total of 311 patients were enrolled, including 63 patients with and 248 patients without hypovascular HCC. Except smaller tumor size in patients with hypovascular HCC (9.4cm versus 10.8cm, p=0.03), the other baseline data was comparable in these two groups.

The overall response rate was 19% (CR: 6.3% PR: 12.7%) and 19% (CR: 7.3% PR: 11.7%) in patients with and without hypovascular HCC (p=0.56). The disease control rate was 25.4% and 37.9% in patients with and without hypovascular HCC (p=0.08). The overall median survival were 6 and 8 months in patients with and without hypovascular HCC (p=0.70). The 3-month, 6-month, and 12-month survival rate were 72.8%, 50.2%, 32.3% in patients with hypovascular HCC and 80.1%, 55.5%, 37.8% in patients without hypovascular HCC (p=0.53).

Conclusions: The treatment outcomes of HAIC seemed to be similar between patients with and without hypovascular HCC.

1

2

1

1

1

1

許柏格 陳嘉邦 蘇培元 陳洋源 徐友春 顏旭亨 1 蘇維文 1 彰化基督教醫院肝膽胃腸科 2 彰化基督教醫院醫學影像科

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in Taiwan. For unresectable liver tumors, according to the current treatment guidelines, there is TAE. In Asia, HAIC has been used for intermediate or advanced stage of HCC (Barcelona Clinic Liver Cancer , BCLC stage B or C), but the effects are still controversial . We set up a modified hepatic arterial infusion chemotherapy (mHAIC) to treat HCC (BCLC stage B) to see if it has any effect.

Aims: To study if there is any treatment response for patients with HCC (BCLC stage B) with mHAIC Methods: We retrospectively 14 patients disgnosed of hepatocellular carcinoma with BCLC stage B from May 1, 2019 to October 1, 2019. All patients must meet the following inclusion criteria: total bilirubin< 3.0 mg/dl, GOT or GPT < 200 IU/L, and platelet count< 50x10^3/ μL. After obtaining the patient’s informed consent, arrange hospitalization and implant the arterial canal in a peripherally inserted central catheters (PICCs) manner, and start the treatment of HAIC. After 5 days of Cisplatin 20 mg / m2 and 5FU 100mg / m2 HAIC, transarterial embolization (TAE) with Lipiodol was arranged after finishing HAIC and then extubated. The above treatment we call modified HAIC. Three weeks later followed by a second HAIC, and then we followed by a three-week computer schedule to evaluated the treatment response with modified Response Evaluation Criteria in Solid Tumors (mRECIST) Results: A total of 13 patients with liver cancer BCLC stage B participated in two HAIC treatments. Alpha fetoprotein (AFP) decreased significantly in 8 patients , and AFP increased in 6 patients, all showed in Figure 1. In the mRECIST 1.1 assessment response, 7 patients achieved complete response (CR), 5 patients achieved partial response (PR), and the remaining 1 achieved stable disease (SD), the study showed CR: 53.8 % , PR: 38.4% and SD: 7.6%.

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P.078 Conclusions: Modified HAIC in our hospital seems to have achieved good results at present, but the sample size is still too small. I hope it can be helpful for patients with liver cancer in the future

末期肝癌的預後分析 - 一醫學中心經驗 PROGNOSIS EVALUATION OF HEPATOCELLULAR CARCINOM BCLC STAGE D- A MEDICAL CENTER EXPERIENCE 陳彥伯 張經緯 王蒼恩 陳銘仁 馬偕紀念醫院肝膽腸胃科 Background: Hepatocellular carcinoma has high prevalence cancer in the past and has a major mortality.

BCLC stage D has a poor outcome(average OS about 3 months) in the past due to traditional systemic treatment such as chemotherapy and loco-regional treatment has poor response to this group. Recently, development of some new target-kinase inhibitor and immunotherapy carry some benefit treatment for advanced hepatocellular carcinoma.

There maybe has some effect to selective group of BCLB stage D patients.

Aims: We try to analysis the factors to predictor the prognosis of BCLC stage D HCC patient. The subgroup of BCLC stage D may has advantage to received new antitumor agent.

Methods: We retrospective review the cancer registration system to collected patients who diagnosed with hepatocellular carcinoma, BCLC stage D from Jan. 2016 to Sep. 2018.

Collect initial C-P score, EGOD and image.. The followed duration was 15 months.

Results: Total 54 patients was met the diagnosis(one patient loss follow-up). Total 5 patients has not reach the end point.

The result showed survival time ranged from 9 to 946 days. Median survival time was 67 days. 6 months overall survival was 24.1%(13/54).

Conclusions: There’s still heterogeneity amoud the BCLC stage D group such the liver reservoir from Child-Pugh 1015 and other cor-morbidity has not including( DM, CAD, Uremia….), the portal hypertension and the heterogeneity of tumor behavior. How to select the subgroup which had long survival time to received new anti-tumor therapy still need more study.

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2020 消化系聯合學術演講年會

P.079

P.080

發炎性腸道病患非酒精性脂肪肝之一醫學 中心病例分析 NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SINGLE MEDICAL CENTER COHORT STUDY

脂肪酸結合蛋白和視黃醇結合蛋白 -4 在慢 性腎臟性疾病的角色 THE ROLE OF FATTY ACID-BINDING PROTEIN (FABP) AND RETINOL BINDING PROTEIN (RBP4) IN CHRONIC KIDNEY DISEASE.

伍麗莎 許翠純 顏旭亨 徐友春 彰化基督教醫院胃腸肝膽科 Background: Increased prevalence of nonalcoholic fatty liver disease (NAFLD) is observed in patients with inflammatory bowel disease (IBD) from the Western country. Both intestinal inflammation and metabolic factors are to contribute to the pathogenesis of IBD-associated NAFLD. The burden of NAFLD is not clear in the Asian population.

Aims: To evaluate the prevalence of NAFLD and liver fibrosis in a cohort of Asian IBD patients.

Methods: From 2019.01 to 2019.07, IBD patients who received ultrasound examination were enrolled. Hepatic steatosis and fibrosis were measured with liver stiffness measurement (LSM ) and controlled attenuation parameter (CAP) using FibroScan. Patients with a history of excessive alcohol or recent steroid use were excluded. Univariate and multivariate analysis were performed.

Results: A total of 37 consecutive patients were enrolled and included in the analysis (19 Ulcerative colitis, 18 Crohn’s disease). The median age was 39-year-old.

The patients had normal weight (51.4%), underweight (24.3%), overweight (18.9%) and obese ( 5.4%). The CAP detected steatosis was S0 (81.1%), S1(8.1%), S2(5.4%) and S3(5.4%). Advanced fibrosis was observed in 8.1% of the patients with LSM ≥ 7. The UC patients has a lower LSM compared with CD patients (4.72 vs 6.01, p =0.02) but similar age, sex and CAP distribution. History of antiTNF usage is associated with a higher LSM (6.13 vs 4.82, p =0.02) but not CAP among these patients.

Conclusions: In this study, the prevalence of NAFLD is low (18.9%) and patients with Crohn’s disease or use of anti-TNF is associated with a higher LSM but not CAP in our study.

1

1,2

1,3

1

1,2

蔡友蓮 楊盈盈 劉志偉 黃祥芬 黃加璋 黃怡翔 1,2 1,2 林漢傑 侯明志 1 臺北榮民總醫院內科部 2 臺北榮民總醫院肝膽腸胃科 3 臺北榮民總醫院風濕免疫科 4 臺北榮民總醫院感染科

1,2

Background: Detection of the chronic kidney disease (CKD) progression can begin early intervention to improve the prognosis. Apoptosis of renal proximal tubular cell is one important pathway to induce the CKD progression.

Accumulation of albumin in kidney leads to accumulate misfolded proteins within endoplasmic reticulum (ER) and induction of ER stress. Prolonged ER stress induced protein that promoting apoptosis, which is closely related to the progression of chronic kidney disease .Biomarkers including fatty acid-binding protein (FABP) and retinol binding protein (RBP4), which are produced from inflamed liver, adipose tissue and immune cells, had been reported to predict the CKD progression and to induced apoptosis in renal cells.

Aims: This in vitro study evaluates the roles of fatty acid-binding protein (FABP) and retinol binding protein (RBP4) in enhancement of albumin-induced and ER stressmediated apoptosis in HK-2 cells/podocytes.

Methods: Incubation with incremental concentrations of bovine serum albumin induced the significant apoptosis of HK-2 cells/podocytes . After 2 hours of BSA pretreatment, BSA-pretreated cells were incubated with increasing concentrations of human recombinant FABP4 (25, 50, 75, 100μg/mL), or human recombinant RBP4 (25, 50, 75, 100μg/mL) for 48 hours for dose response comparisons.

The percentage of cell viability of each treated group was compared to untreated group. Using the same cells of albumin cytotoxicity experiments, Cell lysates of above mentioned cells were used for extraction of proteins [CHOP, phospho-MAPKp38, Bcl-2] and mRNAs [CHOP, SAPK/ JNK, caspase-8, caspase-9] for ER stress and apoptosisrelated markers. These markers are the downstream signals of TNFα-related activation of apoptosis.

Results: Both hrFABP4 and hrRBP4 dose-dependently

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2020 消化系聯合學術演講年會

P.081 enhanced the BSA-suppressed viability of HK-2 cells and podocytes. Similar trends of the enhancement of BSAinduced increases in percentages of caspase+, Tunel+, Annexin-V+PI+ HK-2 cells and podocytes by concomitant incubation of hrFABP4 and hrRBP4. Correspondingly, the co-incubation of hrFABP4 and hrRBP4 have similar trends of increase in the expressions of ER stress and apoptosis markers including CHOP, SPAK/JNK, p38-MAPK, Bcl2, caspase-3,-8,-9 proteins and mRNAs in cell lysates of BSA-pretreated HK-2 cells and podocytes.

Conclusions: This study confirmed that the enhancement of albumin-induced and ER stress-mediated apoptosis by FABP4/RBP4 in human HK-2 and podocytes cell lines.

These results indicated the potential roles of FABP4 and RBP4 as target for therapeutic intervention for CKD progression.

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酒精代謝基因 ALDH2*2 突變可能誘發非酒 精性脂肪肝病和代謝症候群 ALCOHOL METABOLIC GENE ALDH2*2 MUTATION MAY INDUCE NONALCOHOLIC FATTY LIVER DISEASE AND METABOLIC SYNDROME 1

2

2

莊曉莉 楊賢馨 胡瑞庭 1 國家動物中心 2 國泰綜合醫院肝臟中心

Background: Aldehyde dehydrogenase 2 (ALDH2) gene encodes the mitochondrial aldehyde dehydrogenase, a critical enzyme of ethanol metabolism. There is a high prevalence of ALDH2*2 variant and Asian facial flushing syndrome in the Southeast Asia, as high as 45% in Taiwan.

Aims: The role of ALDH2 in modulating non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome are studied.

Methods: 4-5weeks old male and female wild-type C57BL/6JNarl and ALDH2*2 gene knock-in mutant mice (WT-M, ALDH2-M, WT-F and ALDH2-F) were fed a 60% high fat diet (HFD) for 16 weeks (n=5-8).

Results: ALDH2-M has significantly higher body weight (45.4 ± 4.6 g vs 38.5 ± 4.0 g, P= 0.046), white adipose tissue (4.86 ± 0.66 g vs 3.16 ± 1.02 g, P= 0.019), liver weight (1.79 ± 0.29 g vs 1.43 ± 0.22 g, P= 0.04), serum ALT levels (142.9 ± 57.9 iu/L vs 61.3 ± 26.2 iu/L, P= 0.04), HOMA-IR (53.0 ± 22.3 vs 18.0 ± 4.3, P= 0.03) and OGTT (P< 0.05) compared to WT-M. There was no difference in the female including WT-F and ALDH2-F groups. The abundant steatosis and inflammatory cells were observed in ALDH2 group. The levels of cytokines including TNF-α, IFN-γ, IL-2, IL-6 and IL-17 were no difference in all groups.

Conclusions: ALDH2*2 mutation may exacerbate HFDinduced NAFLD and metabolic syndrome in male WT and ALDH2 mice but not in female. Mutation of the alcohol metabolic gene ALDH2 may induce NAFLD and metabolic syndrome in the absence of alcohol consumption. The very high prevalence of ALDH2*2 mutation may be one of the causes of NAFLD and metabolic syndrome in the Southeast Asia. The clinical role of ALDH2*2 mutation is important on the pathogenesis of NAFLD and needs further studies.

2020 消化系聯合學術演講年會

P.082 Interleukin-2 receptor alpha 作為非酒精性 脂肪肝診斷的生物標記 INTERLEUKIN-2 RECEPTOR ALPHA AS A BIOMARKER FOR NONALCOHOLIC FATTY LIVER DISEASE DIAGNOSIS 1,2,3,6,7

4,5

1

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6,7

9.10

高偉育 王偉 林源峰 張宜崴 陳志榮 蘇建維 1 2,3 1,2,3 張育嘉 唐瑞祥 張君照 1 臺北醫學大學臨床醫學研究所 2 臺北醫學大學附設醫院內科部胃腸科 3 臺北醫學大學醫學院內科學科 4 臺北醫學大學附設醫院外科部消化外科 5 臺北醫學大學醫學院外科學科 6 臺北醫學大學附設醫院病理部 7 臺北醫學大學醫學院病理學科 8 臺北醫學大學萬芳醫院病理實驗部 9 臺北榮民總醫院內科部胃腸科 10 陽明大學醫學院醫學系

aspartate aminotransferase, gamma-glutamyltransferase, Fibrosis stage 2-4, aspartate aminotransferase/platelet ratio index, Fibrosis-4 score, fatty liver index, liver stiffness measurement, controlled attenuation parameter, ultrasonographic fatty and fibrosis score than non-NASH group. Multivariate analysis disclosed IHC of IL2RA (Odds ratio, 1.025; 95% confidence interval, 1.006-1.045; P = 0.011) and ALT (Odds ratio, 1.045; 95% confidence interval, 1.018-1.073; P = 0.001) were the independent factor associated with NASH. Conclusions: IL2RA is significantly associated with NASH in NAFLD patients and would be a useful single biomarker for NASH diagnosis.

Background: Two recent studies in the adult and children Nonalcoholic Steatohepatitis-Clinical Research Network (NASH-CRN) cohorts showed soluble interleukin-2 receptor alpha (IL2RA) increased with fibrosis severity.

However, hepatic study should be further elucidated and no study have been conducted in Asian morbidly obese patients underwent bariatric surgery.

Aims: We aimed to use immunohistochemistry (IHC) staining of IL2RA as a biomarker for nonalcoholic fatty liver disease (NAFLD) diagnosis.

Methods: This prospective cohort study enrolled 123 morbidly obese patients underwent bariatric surgery at Taipei Medical University Hospital from October 2016 to June 2018. Preoperative clinical and laboratory data were obtained. During bariatric surgery, all patients underwent a wedge liver biopsy under laparoscopic guidance.

The diagnosis of NASH and liver fibrosis were made histologically. IHC of IL2RA was counted the number of lymphocytes with IL2RA immunoreactivity in 5 high power fields (total 23.76 mm2).

Results: Of the 123 patients, mean age was 35.5 years, mean body mass index was 40.6 kg/m2, 87 (70.7%) were female, 25 (20.7%) had diabetes mellitus, 57 (46.3%; 11 non-NAFLD, 46 steatosis) and 66 (53.7%) were in the non-NASH and NASH groups. 57 (46.3%; 11 nonNAFLD, 46 steatosis) and 66 (53.7%) were in the nonNASH and NASH groups. Patients in the NASH group had larger waist circumference, higher IHC of IL2RA, fasting glucose, alanine aminotransferase (ALT),

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2020 消化系聯合學術演講年會

P.083 鑑定非酒精性脂肪肝沒有脂肪肝炎的病態 性肥胖病人增加顯著肝纖維化敏感性之目 標基因 IDENTIFICATION OF TARGET GENES INCREASE SUSCEPTIBILITY OF SIGNIFICANT LIVER FIBROSIS IN MORBIDLY OBESE PATIENTS WITH NONALCOHOLIC FATTY LIVER WITHOUT STEATOHEPATITIS 1,2,3,6,7

11

4,5

7,8

6,7

高偉育 許博凱 王偉 張宜崴 陳志榮 9,10 1 2,3 1,2,3 蘇建維 張育嘉 唐瑞祥 張君照 1 臺北醫學大學臨床醫學研究所 2 臺北醫學大學附設醫院內科部胃腸科 3 臺北醫學大學醫學院內科學科 4 臺北醫學大學附設醫院外科部消化外科 5 臺北醫學大學醫學院外科學科 6 臺北醫學大學附設醫院病理部 7 臺北醫學大學醫學院病理學科 8 臺北醫學大學萬芳醫院病理實驗部 9 臺北榮民總醫院內科部胃腸科 10 陽明大學醫學院醫學系 11 臺北醫學大學附設醫院醫學研究部

Background: The prevalence rate of nonalcoholic fatty liver disease (NAFLD) has been reported up to 74% to 90% of morbidly obese patients. The fibrosis status for steatosis usually is mild (F0-F1). However, a recent large crosssectional liver biopsy cohort from patient with NAFLD study showed one-third patients with significant fibrosis had no non-alcoholic steatohepatitis (NASH).

Aims: This study is aimed to identify target genes for predicting significant liver fibrosis in morbidly obese patients with nonalcoholic fatty liver without steatohepatitis based on bioinformatics analysis.

Methods: The Gene Expression Omnibus (GEO) is a database repository of sequence- and array-based data.

We used the keywords “bariatric surgery”, “nonalcoholic steatohepatitis” to search the GEO repository. There were five datasets used in this study from GEO database, such as GSE66676, GSE61256, GSE48452, GSE49541 (four microarray data), and GSE130970 (RNA sequencing data).

We used GSE130970 as training set to distinguish patients into NASH and steatosis groups. Three arrays (GSE66676, GSE61256, and GSE48452) with NASH and steatosis annotation were used to validate capabilities of these genes, and the other one (GSE49541) only be annotated fibrosis stages including F0-F1 and F3-F4 was further utilized to

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speculate fibrosis status of NASH and steatosis groups. We selected the specific differentially expressed genes (DEGs) between mild and advanced fibrosis in steatosis and NASH which exhibited a 1.5-fold change (FC >1.5-fold) and a p value of <0.05 from limma package.

Results: Consequently, FBXO46, EEF1A2, FEN1, HTR7, IGSF11, NUDT10, and TTC21A were selected to construct this prediction model of NASH and steatosis groups. The prediction model was applied to GSE49541 dataset, there were 18 patients with NASH and 18 patients with steatosis by setting cutoff predicted probabilities at first quartile (less than it would be recognized as steatosis) and third quartile (larger than it would be recognized as NASH).

Thus, of 11 potential steatosis patients have mild fibrosis and 7 ones have advanced fibrosis, and 6 potential NASH patients have mild fibrosis and 12 ones have advanced fibrosis. There were 244 and 270 DEGs were identified in steatosis and NASH, respectively. Finally, we identified interleukin-13 receptor alpha 2 (IL-13Rα2) was highly expressed in steatosis with advanced fibrosis relative to mild fibrosis, but lowly expressed in NASH with advanced fibrosis relative to mild fibrosis. Moreover, DEGs analysis between steatosis and NASH with advanced fibrosis could also show that IL-13Rα2 was significantly up regulated in steatosis with advanced fibrosis.

Conclusions: IL-13Rα2 might be a biomarker to shed light in realizing potential different mechanism to make patients with NAFLD to develop fibrosis. Further clinical cohort studies are warranted to investigate the predicted biomarkers and pathways using online databases in morbidly obese patients undergoing bariatric surgery.

2020 消化系聯合學術演講年會

P.084 脂 肪 肝 係 數 (FLI) 及 可 控 衰 減 參 數 (Controlled Attenuation Parameter, CAP) 與 代謝症候群分級之關聯 一社區研究 THE ASSOCIATION OF FATTY LIVER INDEX (FLI) AND CONTROLLED ATTENUATION PARAMETER (CAP) ON METABOLIC SYNDROME (METS) STAGE- A COMMUNITY STUDY 1,2

3

1, 2

張麗文 Bagas Suryo Bintoro 林裕民 3 白其卉 1 新光吳火獅紀念醫院胃腸肝膽科 2 輔仁大學醫學系 3 臺北醫學大學公共衛生學系

1

孫灼基 楊國卿

1

Background: The fatty liver index (FLI), an algorithm comprising body mass index (BMI), waist circumference, gamma-glutamyl transferase (GGT) and triglyceride concentrations, is frequently used for hepatic steatosis evaluation. Controlled attenuation parameter (CAP) implemented in FibroScan® is a recent method for noninvasive assessment of hepatic steatosis, a finding often found in patients with metabolic syndrome (MetS).

Aims: To elucidate the association of FLI and CAP on the MetS stage and its components in a community based cohort.

Methods: A total of 170 non-viral hepatitis subjects (102 males, 68 females) with a mean age of 63.6 + 9.6 y/o from a community-based cohort were analyzed. All of the participants received demographic survey and laboratory tests including complete blood count, biochemistry, abdominal ultrasonography and FibroScan® examination.

Liver steatosis was assessed by using FibroScan® and classified into four quartile of CAP value (Q1: <=231 / Q2: 232-277 / Q3: 278-306 / Q4: >= 306 dB/m). FLI was derived using standard equation and also categorized in quartile (Q1: <=7.69/ Q2: 7.7-15.19 / Q3: 15.2-30 / Q4: >=30). Data on five components of MetS (glucose intolerance, elevated BP, elevated TG, reduced low highdensity lipoprotein (HDL) and central obesity) were also obtained. We defined MetS components by using Harmonized criteria and classified as stage according to CardioMetabolic Alliance with slight modification (Stage A: non MetS components, Stage B: 1-2 MetS components, Stage C: combination of subject with MetS diagnosis or FLI >60 or diabetes by FPG >=126 and HbA1C >6.5).

Student’s t-test and Fisher exact test were used to determine their differences in terms of sex. We employed ordered

logistic regression by using the lowest quartile as reference to calculate the odds ratios (ORs) and 95% confidence interval (95% CI) of the outcomes. First, we calculated crude ORs and then developed a model adjusted for sex, age (Model 1), in addition to BMI final model (Model 2).

P-value <0.05 is considered as significant.

Results: Female subjects have lower levels of blood pressure, waist circumference, glutamic pyruvic transaminase (GPT) and gamma glutamyl transpeptidase (GGT); and higher HDL value than male subjects. The distribution of MetS stage A, B and C was 45 (26.5%), 77 (45.3%), 48 (28.2%) respectively. The higher the FLI or CAP category, the less proportion in the non- MetS (MetS stage A), but the higher proportion in the MetS stage C. In addition, higher FLI and CAP category also have higher proportion of subjects defined as abnormal in each MetS component. Each quartile increase on FLI and CAP was associated with increased likelihood of having higher MetS stage (FLI: Crude OR 2.69 (1.99-3.64), Model 1 OR 2.9 (2.10-4.01), and Model 2 OR 2.73 (1.73-4.30); CAP: Crude OR 1.89 (1.44-2.49), Model 1 OR 1.92 (1.45-2.53), Model 2 OR 1.49 (1.10-2.02)).

Conclusions: Our research shows that FLI and CAP are positively correlated with the MetS stage and its components. FLI and CAP may be indicators of MetS risk and can be used for MetS screening; however, their predictive performance is worthy of further research in the future.

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P.086

地中海飲食對非酒精性脂肪肝效療評估：統 合分析 THE EFFECTIVENESS OF MEDITERRANEAN DIET IN INDIVIDUALS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

新興的脂肪肝診斷輔助工具：腹部超音波上 的深度學習 DEEP LEARNING IN ABDOMEN ULTRASOUND: A NEW DIAGNOSTICAIDED SYSTEM FOR FATTY LIVER

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李騏宇 林揚笙 方靜如 張雅惠 陳銘仁 王鴻源 1 馬偕醫院內科部 2 馬偕醫院胃腸肝膽科 3 馬偕醫院藥劑部 4 國立成功大學醫學院附設醫院

Background: Currently, the cornerstone of therapy for NAFLD is lifestyle modification, including diet modification to achieve weight loss. lWhile the Mediterranean diet has been widely researched in the context of cardiovascular disease, there are limited data evaluating its impact in patients with NAFLD. Aims: To determine the effect of Mediterranean diet in Individuals with NAFLD. Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (Cochrane CENTRAL) and Scopus from inception to October 2019; without publication date or language restrictions.

Randomized controlled trials of Mediterranean diet versus placebo or other treatment for the adult patients with NAFLD were selected. The outcome was the effect of the Mediterranean diet on changes in histological, radiological, biochemical markers of NAFLD. Results: Mediterranean diet showed significant reduction of weigh in MD group compared with non-MD group. The mean difference was -2.12 [ 95% CI -3.70, -0.54, p value = 0.009). In addition, Mediterranean diet had significant improvement of hepatic fibrosis by Fibroscan with a MD of -1.45 [ 95% CI -1.93 to -0.97, p value < 0.001).

Conclusions: Mediterranean diet might have benefit for reduction of weight and decrease of hepatic fibrosis.

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周宗賢 張君照 1 臺北醫學大學附設醫院內科部消化內科 2 臺北醫學大學內科部消化內科 Background: The convolutional neural networks (CNNs) is a Feed Forward Neural Network (FFNN) and is designed based on an animal’s visual cortex which focus on overlapping tile shape region. It has been used wildly in image/video recognition, recommender system, natural language processing, chest and Go. Though, this technology is new in Medical field, it might help us in image diagnosis.

Aims: We aim to utilize convolutional neural networks (CNNs) and abdominal ultrasound image to distinguish the grades of fatty liver.

Methods: We use object classification technology to detect the grade of fatty liver by VGG19 neural network and manually annotate special features on ultrasound image, including the feature of bright parenchyma with increased liver to kidney contrast, and the feature of far attenuation of the ultrasound beam, and the feature of obscure vessel wall, and the feature of blurred gallbladder wall, and the feature of obscure contour of the diaphragm as the network input data. We use two kinds of classification method on VGG19, one is two class classification which will detect whether the patient with fatty liver or not, the other is four class classification which will differentiate four grades of fatty liver including no fatty liver, mild fatty liver, moderate fatty liver and severe fatty liver.

Results: By well-tuned VGG19 neural network, the four grade classification archives 87.2% accuracy, 87.1% sensitivity and 95.8% specificity on 13,000 ultrasound image. And the two class classification archives 94.7% accuracy.

Conclusions: CNNs is an incredible technology that allowed us to increase our detection rate in image study.

Other than the fatty liver disease, it can also be use in many different ways, such as detecting liver nodules/ tumors/cystic lesions, gallbladder lesions, etc. It allowed us to perform medical practice even in remote areas, where specialist is lacking. However, there are still several limitations we need to face. The accuracy for classifying

2020 消化系聯合學術演講年會

P.087 the four grade fatty liver is still not met the target (Both sensitivity and specificity need to be > 90%). It still needs several modifications and more images training in order to achieve these targets. The classification and detection of lesions by CNNs is not simultaneous and require more tuning before it can be commercialized.

細菌性肝膿瘍的特徵與處置 – 在臺北市萬芳 醫院的一年期回顧性病例對照研究 CHARACTERISTICS AND MANAGEMENT OF PYOGENIC LIVER ABSCESS – A ONE-YEAR RETROSPECTIVE CASE-CONTROL STUDY IN WAN FANG HOSPITAL 1,2

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黃柏瑞 翁翊媗 張智翔 吳明順 粟發滿 連吉時 1 臺北市立萬芳醫院內科部消化內科 2 臺北市立萬芳醫院內科部

Background: Pyogenic liver abscess (PLA) is a suppurating infection of the liver parenchyma and varies from 8 to 22 patients per 1,000,000 people belonging to a geographic area with substantially higher rates reported in Taiwan.

Aims: Wan Fang Hospital was a medical center in Taipei that provided major medical service to Southern Taipei. Since the lack of clear risk factors of the PLA, we performed this study, aiming to review a local medical center’s experience in Epidemiological, clinical patterns, and management of PLA. Methods: We provided a retrospective, descriptive case series in a single-center assessing demographic characteristics, presentation patterns, etiological factors, microbiological etiology, and management for patients treated for PLA between September 2018 to September 2019. The statistical analysis and comparisons of the variable were made with standard statistical tests. All statistical analyses were performed using SPSS 22.0 software. Results of continuous variables are expressed as mean ± standard deviation. The significance level for all statistical tests was set at 0.05 two-tailed.

Results: From September 2018 to September 2019, there were 44 cases that were treated at Wan Fang Hospital for PLA treatments. 24 patients (54.5%) were male and 20 (45.5%) patients were female The patient’s age was ranging from 31 to 93, and the mean age was 66.6 (standard deviation, SD: ± 14.8). The average admission duration was 21.4 days (3-112). The majority of patients with PLA presented with fever, 86.3% (38), following with chillness in 19 patients (43.2%), right upper abdominal pain in 19 patients (43.2%), nausea or vomiting in 9 patients (20.4%), anorexia in 8 patients (18.2%), shortness of breath in 7 cases (16.0%) and headache in 4 patients (9.1%).

There were 13 patients (29.5%) who had diabetes mellitus and 8 (18.2) patients who were diagnosed with

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P.088 gastrointestinal cancer including hepatocellular carcinoma, gastric cancer, Ampulla Vater cancer, and pancreatic cancer. The mortality rate of these patients was 15.9% (7), and five of them (85.7%) died in sepsis and the other two patients (14.3%). According to the abdominal computed tomography and abdominal sonogram, there were 20 patients (45.5%) with abscess smaller than 5cm and 21 patients more than 5cm (47.7%). Interesting, there are 3 patients (6.8%) who were diagnosed hepatic abscess after radiofrequency ablation (RFA) which were difficult to measure the actual size of the liver abscess.

The most common laboratory abnormality among included items was increased C-Reactive Protein (CRP, 19.14mg/dL, ranging from 0.5-36.3mg/dL) and white blood cells (17000/ cumm, ranging from 950-94100/cumm). Abnormal liver function including GOT (69.4U/I, ranging from 14~436 U/ I), GPT (91.58 U/I, ranging from 7~733 U/I), total bilirubin (1.53 mg/dl, ranging from 0.38-9.1 mg/dl) and alkaline phosphatase (145U/l, ranging from 58~362 U/l).

We observed a pus-culture study in 44 cases of which only 20 cases (45.4%) came with positive microbial reports.

Culture from an aspirate of the liver abscess was positive in 20 of 44 patients who underwent percutaneous aspiration of liver abscess (positive rate, 45.4%). The most common organism identified was KL. Pneumoniae (34%), followed

by Strep.constellatus (6.8%), and E Coli (4.5%).

Besides antibiotics treatment, patients diagnosed with PLA received image-guided aspiration or catheter drainage depending on the clinical condition. There were 3 patients received both needle aspiration and drainage catheter during admission (6.8%), 12 patients received needle aspiration alone (27.3%), 13 patients received catheter drainage (29.5%) and 16 patients received conservative treatment alone (36.4%).

Conclusions: This study provided first-hand original experiences in this field to show provide useful information. In practice, clinicians should maintain a high index of suspicion for PLA in patients who present with the risk factors; in particular, clinical scenarios of fever, right abdominal pain, increased levels of C-reactive protein, white blood cell count and liver enzymes. Prompt diagnosis of liver lesion and administration of antibiotics and percutaneous drainage or aspiration can conduce to successful treatment.

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溴化西曲銨通過調節規範性和非規範性 TGF-β 信 號 通 路 抑 制 人 體 肝 臟 SK-HEP-1 細胞的遷移和侵襲 CETRIMONIUM BROMIDE INHIBITS CELL MIGRATION AND INVASION OF HUMAN HEPATIC SK-HEP-1 CELLS THROUGH MODULATING THE CANONICAL AND NON-CANONICAL TGF-β SIGNALING PATHWAYS 1

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陳忠宏 顏聖烈 李嘉仁 1 彰濱秀傳醫院胃腸科 2 童綜合醫院醫研部

Background: Cetrimonium bromide (CTAB) a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated.

A i m s : To i n v e s t i g a t e d w h e t h e r C TA B i n h i b i t s cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells.

Methods: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis.

Results: SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SKHEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-cadherin, Smad2, Smad3, Smad4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, β-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signalregulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3β. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-β (TGF-β) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-β signaling including MAPK pathways

2020 消化系聯合學術演講年會

P.089 like ERK1/2, p38 MAPK, JNK and PI3K. Conclusions: CTAB is involved in the suppression of TGF-β- mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.

南臺灣急性 A 型肝炎之臨床表徵 CLINICAL FEATURES OF HEPATITIS A IN SOUTHERN TAIWAN 1

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許博堯 梁博程 黃釧峰 葉明倫 黃駿逸 林子堯 1,2 1,2 1,2 1,2 1,2 陳信成 黃志富 莊萬龍 余明隆 戴嘉言 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學院內科學院

1

Background: Acute hepatitis A is caused by the hepatitis A virus (HAV). HAV infection is usually a self-limited illness that does not become chronic. Even though the incidence of fulminant hepatitic failure is low, it deserved our attention to investigate the clinical characteristics of patients with acute hepatitis A. Aims: To analyze the clinical characteristics of patients with acute hepatitis A Methods: From September 2009 to June 2018, the patients diagnosed with acute hepatitis A in the hospitals of the high medical system were analyzed. Analysis items included age, gender, weight, BMI, laboratory data, incidence of hospitalization and length of stay, prevalence of chronic liver disease and mortality rate.

Results: From September 2009 to June 2018, 42 patients diagnosed with acute hepatitis A were enrolled in the single teaching hospitals, with an average age of 33.6 years and 85.7% male gender. The median value of total bilirubin measured at the beginning of admission was 5.4 mg/dl, and the median peak value was 6.5 mg/dl, which took an average of 2.1 days. The median AST measured at admission was 577 U / L, and the median peak value was 680 U / L, with an average duration of 0.7 day. The median ALT level measured at admission was 1384 U / L, and the median peak level was 1384 U / L, with an average duration of 0.4 days. Decompensation was defined as total bilirubin ≥ 2 mg / dl or prothrombin time (PT) prolong ≥ 3 seconds. The incidence of decompensation was 78.6%.

Among these patients with acute hepatitis A, 3 were HBsAg-positive (7.1%), 4 were anti-HCV-positive (9.5%), and only 1 (2.4%) had chronic liver disease. No patients had liver cirrhosis. Twelve patients were HIV-positive (28.6%), and all of them were detected between 2016 and 2018 (accounting for 41.4% of patients with acute hepatitis A in 2016-2018). Thirty four patients (80.1%) were hospitalized, with an average hospital stay of 9.4 days.

Six people used SNMC during admission, and the average duration of use were 5.3 days. Only one patient died (2.4%).

Conclusions: Patients with acute hepatitis A were mainly

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第二部分：消化道及膽胰疾病 P.090 young men, and the vast majority of patients had no chronic liver disease. Most patients visiting the hospitals suffered from hepatic decompensation and were hospitalized.

Fortunately, most of them were cured and discharged. As many as 41.4% of patients with acute hepatitis A diagnosed after 2016 have also been tested positive for HIV.

糖尿病與胰臟癌病人死亡率的相關性研究 PROGNOSTIC IMPACT OF DIABETES MELLITUS ON OVERALL SURVIVAL IN A NATIONWIDE POPULATIONBASED COHORT OF PATIENTS WITH PANCREATIC CANCER 1,2

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曾兆明 許耀峻 王文 李青泰 戴啟明 曾政豪 1 義大癌治療醫院肝膽胰內科 2 義大醫院肝膽胰內科

Background: Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. Previous studies were limited by the mixture of patients with long-lasting and new-onset DM Aims: We aimed to clarify the association between DM and the risk of mortality in patients with pancreatic cancer.

Methods: This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM within 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (>2 years) and non-diabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed Results: Patients with long-standing DM were significantly older (mean age, 71.38 vs. 66.0 years, P < 0.0001) and had a higher Charlson comorbidity index (9.53 vs. 6.78, P < 0.0001) and diabetes comorbidity severity index (2.38 vs.

0.82, P < 0.0001) compared with the non-DM controls.

Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.20–1.33, P < 0.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95–1.06, P = 0.84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.

Conclusions: After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.

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管內超音波在非腫瘤情況下的臨床應用 CLINICAL APPLICATIONS OF INTRADUCTAL ULTRASOUND IN NONTUMOR CONDITIONS

內視鏡逆行性膽胰管攝影術中壺腹乳頭的 型態會影響壺腹插入成功率 DUODENAL MAJOR PAPILLA MORPHOLOGY CAN AFFECT BILIARY CANNULATION SUCCESSFUL RATE DURING ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHY AND PANCREATOGRAPHY

林連福 黃彼得 肝膽腸胃科, 內科部, 童綜合醫院 Background: Besides tumor staging, and bile duct stricture, Intra-ductal ultrasound (IDUS) has been applied in small common bile duct (CBD) stones (<8mm) with negative cholangiogram, in the diagnosis of Mirizzi syndrome (MS), and in idiopathic pancreatitis [Am J Gastroenterol 2005; 100: 1051–1057 Endoscopy 2015; 47: 739–753. Endosc Ultrasound. 2016;5: 291–299.].

Aims: To report the experience of intra-ductal ultrasound (IDUS) in non-tumor conditions.

Methods: From June 2011 to August 2019, 9 cases of IDUS for non-tumor indication were analyzed retrospectively.

The inclusion criteria include: (1) Positive findings of small CBD stone on IDUS with negative cholangiogram; (2) Positive finding of stone at narrow extrinsic compression of hepatic duct region; (3) Positive finding in idiopathic recurrent pancreatitis with IDUS examination. The exclusion criteria were: biliary stricture, tumor staging. IDUS examination was performed during endoscopic retrograde cholangiopancreatography (ERCP) after cholangiogram. The definition of types of Mirizzi syndrome was according to Csendes et al. [ Br J Surg 1989; 76:1139]. The instruments used were Olympus TJF 260V, IDUS Olympus UM-G2029R model Results: Five cases of suspected CBD stone, all female patients, with a mean age of 63 (58-68 year) were proved to have small CBD stone with negative cholangiogram. The mean stone size was 0.47cm (0.23-0.7cm), with 2 small CBD stones in one case, and the mean diameter of CBD was 1.2cm (1-1.4cm). Three cases of biliary obstruction (2 male, and 1 female patients) with a mean age of 53.3 (29-68 year) were diagnosed to have type I Mirizzi syndrome, proved by surgery. The cholangiogram revealed extrinsic compression at common hepatic duct, and IDUS demonstrated stone at the narrow common hepatic duct region. Abdominal CT were non-informative in these 3 Mirizzi syndrome. In the idiopathic recurrent pancreatitis patient, with 5 episodes of acute pancreatitis in the previous 2 year-period, the IDUS revealed CBD sludge. Endoscopic biliary sphincterotomy, and CBD sludge was extracted, and she was free from acute pancreatitis for 8 years.

Conclusions: Intra-ductal ultrasound (IDUS) is helpful in non-tumor conditions like small CBD stones, with negative cholangiogram, diagnosis of Mirizzi syndrome and recurrent idiopathic pancreatitis.

陳柏翰 童春芳 彭彥鈞 黃耀光 蔡炘儒 葉宏仁 張繼森 陳家昌 臺中榮民總醫院胃腸科 Background: Selective biliary cannulation (SBC) is a technical demanding procedure and the most important part of endoscopic retrograde cholangiography and pancreatography (ERCP). It also carries significant risk for complications. There were several risk factors for failing SBC. Aims: We want to determine if duodenal major papilla morphology could be one of the risk factor for failing SBC and post ERCP complications.

Methods: We used Haraldsson’s classification for papilla morphology. Four groups of papilla was Regular (Type 1), Small (Type 2), Protruding or Pendulous (Type 3) and Creased or Ridged (Type 4). Patients were included if they were arranged for therapeutic ERCP and had naïve major duodenal papilla. Included subjects were recorded about the papilla type, ERCP procedure details, indications, demographic data, procedure result and complications.

Risk factors for failing SBC and post ERCP complications were analyzed with multivariate analysis.

Results: There were totally 286 cases included in final analysis. Age, gender, indications for ERCP and therapeutic procedures were not different in four types of papillae. In multivariate analysis, there are higher failing rate in the Type 2 papilla (odds ratio 7.18, p= 0.045) and the Type 3 papilla (odds ratio 7.44, p= 0.016) compared to Type 1 papilla. Both malignancy related obstruction (odds ratio 4.45, p=0.014) and age(odds ratio=1.06, p=0.010) carries risk for cannulation failure compared to stone.

Conclusions: Both small papilla(Type 2) and protruding or pendulous pappila (Type 3) compared to regular papilla(Type 1) are risk factors for failing biliary cannulation.

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P.093 有症狀的膽結石病人有較高的胰臟癌風險 SYMPTOMATIC CHOLELITHIASIS PATIENTS HAVE INCREASED PANCREATIC CANCER RISK- A POPULATION BASED STUDY 1,2

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汪奇志 曾明性 楊子緯 陳宣怡 蘇章政 陳威良 4,5 1,2 林俊哲 蔡明璋 1 中山醫學大學醫學系 2 中山醫學大學附設醫院肝膽腸胃科 3 中山醫學大學醫學資訊學系 4 中國醫藥大學附設醫院內科 5 中國醫藥大學醫學系

Background: Pancreatic cancer is a fatal disease, and only surgical resection at a very early stage can guarantee long term survival. The current risk factor survey is not suitable for sporadic pancreatic cancer that lacks obvious family history or genetic analysis data.

Aims: The aim of the present study was to evaluate the roles of cholelithiasis and cholelithiasis treatments, like endoscopic procedures and cholecystectomy, on pancreatic cancer risk.

Methods: Symptomatic patients over 18 years old with an index admission of cholelithiasis diagnosis were selected from one million random samples from the National Health Insurance Research Database obtained between January 2005 and December 2009. Exclusion criteria included pancreatic cancer, benign neoplasm or anomalies of the pancreas, or endoscopic sphincterotomy/endoscopic papillary balloon dilatation (ES/EPBD), cholecystectomy (CCY), or lithotripsy in 2004. The control group was matched in a 1:1 ratio for sex, age, and strong pancreatic cancer risk factors of chronic pancreatitis and pancreatic cystic disease. The study group was divided into ES/EPBD, CCY, ES/EPBD&CCY, and no-intervention groups for subsequent pancreatic cancer evaluation.

Results: The cholelithiasis group included 8,265 adult symptomatic cholelithiasis cases and the control group included 8,265 matched cases. The cholelithiasis group contained 86 (1.04%) cases of diagnosed pancreatic cancer and the control group contained 8 (0.10%) cases (p<0.001).

Exclusion of pancreatic cancer cases diagnosed in the first 6 months after index admission still resulted in a significantly higher pancreatic cancer rate in the cholelithiasis group (0.22%) than in the control group (0.05%) (p=0.003). The subsequent pancreatic cancer rates were similar, at 0.17%, 0.11%, 0.26%, and 0.29%, in the ES/EPBD, CCY, ES/

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EPBD&CCY, and no-intervention groups, respectively.

Conclusions: Symptomatic cholelithiasis is a risk factor for pancreatic cancer, and the risk after cholelithiasis diagnosis is similar regardless of the intervention (ES/EPBD, CCY, ES/EPBD&CCY, or no invasive intervention).

2020 消化系聯合學術演講年會

P.094 內視鏡十二指腸乳頭大球囊擴張術與內視 鏡括約肌切開術清除大型膽總管結石的比 較：隨機對照試驗的系統性文獻回顧與統合 分析 COMPARISON OF ENDOSCOPIC PAPILLARY LARGE BALLOON DILATATION WITH ENDOSCOPIC SPHINCTEROTOMY IN CLEARING LARGE COMMON BILE DUCT STONES: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS 鄭照霖 吳明順 粟發滿 連吉時 臺北市立萬芳醫院- 委託財團法人臺北醫學大學辦理 Background: Common bile duct stones (CBDSs) are a disease of retained stones within the common bile duct which could lead to lethal complications. Commonly used treatments for CBDSs are: 1. endoscopic sphincterotomy (EST), 2. endoscopic papillary large-balloon dilatation (EPLBD), and 3. EST plus EPLBD. Despite many empirical studies conducted to compare the three treatments, only few studies have focused on comparing EPLBD and EST alone. A systematic review on this topic could not be found. Therefore, the authors have designed this meta-analysis to supplement the missing information in the field.

Aims: The purpose of this meta-analysis is to compare outcomes of EPLBD and EST with the clearance of large CBDSs, adverse events, and use of mechanical lithotripsy Methods: This study was conducteased on the PRISMA statement. PICO (participant/intervention/comparison/ outcome) was established as follows: 1) participants: patients had large CBDSs (> 10 mm); 2) intervention: EPLBD; 3) comparison: EST; and 4) outcomes: the primary outcomd be was the efficacy of removing stones, and secondary outcomes included the complication rate and frequency of using ML. The statistical analysis was performed with Review Manager vers. 5.3. Data synthesis of primary and secondary outcomes was conducted with the dichotomous data type in the risk ratio and 95% confident intervals (CIs). Heterogeneity was calculated by a Chisquared test with a p value of ≤ 0.1, and I2 with a cutoff of ≥ 50% indicating significant heterogeneity. A random-effect model was used because the clinical heterogeneity was not negligible.

Results: Among these six eligible studies, 762 patients’

cases were used for the analysis. Of these patients, 378 underwent EPLBD and 384 underwent EST for clearance of CBDSs. These studies were conducted in four countries: two from China, one each from Korea, Japan, and Egypt.

All six selected articles have indicated the clearance rate of common bile duct stone during the first session of ERCP. The results showed no statistical significance between EPLBD group and EST group (RR = 1.02, 95% CI 0.931.12). There was no statistical significance when comparing overall complications (RR = 1.01, 95% CI 0.71-1.43), pancreatitis (RR = 1.05, 95% CI 0.59-1.89), or bleeding (RR = 0.52, 95% CI 0.23-1.20) between EPLBD and EST groups. There is no significant need for frequent usage of ML existing between the two groups between the two groups.

Conclusions: This study has revealed that EPBLD alone is an effective and safe procedure for treating large CBDSs. Compared to EST, it has foreseeable advantages of clearing stones in one session and reducing the frequency of ML use.

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P.095

P.096

營養治療對於急性胰臟炎感染率之影響：隨 機對照試驗統合分析之系統性文獻回顧 INFECTION RATE AMONG NUTRITIONAL THERAPIES FOR ACUTE PANCREATITIS: A SYSTEMATIC REVIEW WITH NETWORK METAANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

年齡小於 50 歲合併代謝症候群與肥胖者有 較高機率發生膽結石 METABOLICALLY ABNORMAL OBESITY PREDICTS HIGHER RISK OF DEVELOPING GALLSTONE DISEASE IN ADULTS UNDER 50 YEARS

蘇怡佳 張君照 臺北醫學大學附設醫院內科部消化系 Background: Infection in acute pancreatitis (AP) is associated with nutritional therapies including nasogastric (NG), naso-jejunal (NJ), and total parenteral nutrition (TPN). To examine infections among NG, NJ, TPN, and no nutritional support (NNS) in treating patients with AP. Aims: This study aimed to determine the safety of different nutritional route for acute pancreatitis through network meta-analysis of infectious complications Methods: The investigators completed comprehensive search in the Cochrane library, EMBASE, PubMed, Web of Science, and ClinicalTrials.gov without restriction on language and publication date before January 21, 2019.

They also searched the reference lists of relevant studies for randomized controlled trials (RCTs) comparing NG, NJ, TPN, and NNS among patients with AP. Quantitative synthesis was conducted in a contrast-based network metaanalysis. To clarify effects, a network meta-analysis was conducted to calculate the surface under the cumulative ranking curve (SUCRA). Beside of overall infections, the event rates of infected pancreatic necrosis, bacteremia, line infection, pneumonia, urinary tract infection, and other types of infections were measured.

Results: The network meta-analysis of 16 RCTs showed that NJ had significantly lower overall infection rates compared with TPN (risk ratio: 0.59; 95% confidence interval: 0.38, 0.90); and NG had a larger effect size and higher rank probability compared with NJ, TPN, and NNS (mean rank = 1.7; SUCRA = 75.8). TPN was the least preferred (mean rank = 3.2; SUCRA = 26.6).

Conclusions: NG and NJ may be preferred therapies for treating patients with AP. Clinicians may consider NG as a first-line treatment for patients with AP (including severe AP) and even in patients receiving prophylactic antibiotics.

In addition, we found that NNS should be avoided when treating patients with severe AP.

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1

蘇培元 顏旭亨 徐友春 許秋婷 蘇維文 1 彰化基督教醫院胃腸肝膽科 2 彰化基督教醫院內科研究中心

Background: Age, obesity, and metabolic syndrome are known risk factors for gallstones; however, the combined impact of these different risk factors on gallstone formation has not been examined.

Aims: We try to analyze the effect of obesity and metabolic syndrome on gallstones in younger and older participants.

Methods: This retrospective, cross-sectional study involved 3,190 participants who received voluntary physical checkups, including 207 participants (6.5%) with gallstones and 986 participants (30.9%) with metabolic syndrome. Obesity was defined as BMI ≥ 25 kg/cm2. Participants were divided into four groups according to metabolic syndrome and obesity status: 1,633 (51.2%) participants were metabolically healthy and non-obese (MHNO); 571 (17.9%) participants were metabolically healthy but obese (MHO); 292 (9.2%) participants were metabolically abnormal but not obese (MANO); and 694 (21.8%) participants were metabolically abnormal and obese (MAO).

Results: The MAO and MANO groups had more gallstones than the MHO and MHNO groups, regardless of age (<50 or ≥50 years old). The rate of gallstones was similar in younger participants (< 50 years old) in the MAO phenotype compared to older participants (≥50 years old) in the MHNO phenotype (7.2% vs. 6.8%; P = 0.837). Age, HCV infection and four phenotypes were the risk factors for gallstones after non-parsimonious multivariable logistic regression.

Multivariate analyses showed grouping was the independent risk factor for gallstones in participants <50 years old [odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.39–2.43].

Younger participants also had a higher risk of gallstones in the MAO (OR = 7.53, 95% CI = 2.99–18.96), MANO (OR = 5.24, 95% CI = 1.07–25.77), and MHO (OR = 3.45, 95% CI = 1.47–8.06) groups than the MHNO group.

Conclusions: Our retrospectively registered results demonstrate an increased risk of gallstones in younger people (<50 years old) associated with metabolic syndrome and/or obesity. Diet and exercise intervention may be beneficial for high-risk groups to prevent gallstone formation.

2020 消化系聯合學術演講年會

P.097 遠端良性膽管狹窄與遠端膽管癌在 WHIPPLE 手術前的比較 -- 一個醫學中心 的經驗 CHARACTERISTICS OF BENIGN DISTAL BILIARY STRICTURE COMPARING TO DISTAL CHOLANGIOCARCINOMA BEFORE WHIPPLE PROCEDURE: A CENTER’S EXPERIENCE. 1

2

陳俊璋 黃信閎 楊志偉 1 三軍總醫院 2 振興醫院

1

Background: To distinguish benign distal biliary stricture (DBS) from distal cholangiocarcinoma (DCC) always shows a difficult challenge. Approximately 20% of patient undergoing whipple procedure for suspected biliary malignancy are finally with benign etiology. At present, no specific laboratory data or image can ascertain the DBS and DCC. Although the routinely technique of endoscopic retrograde cholangiopancreatography (ERCP) may help us to get biliary sampling for pathology, the missing rate is still disturbing. Besides, newer endoscopic techniques are developing, such as intra-ductal ultrasound and singleoperator cholangioscopy, but are often cost-expensive and with relatively higher rate of post-procedure cholangitis.

Aims: By evaluating the laboratory data, radiological image, and etiology, we hope for possible predictors to distinguish between DBS and DCC. Methods: We collected the people who underwent the whipple procedure since 2007 to 2019. Only patients with pathological diagnosis of DCC and DBS were enrolled.

We calculated the level of AST, ALT, total bilirubin, alk-p, albumin, CEA, and CA199. We also recorded the history of undergoing cholecystectomy, maximal CBD diameter, and CHD diameter by measuring from abdominal CT and MRI. We also calculated the change of CBD diameter by subtracting 1.1 cm in patient with cholecystectomy or by substracting 0.7cm in patient without cholecystectomy, which CBD gradient was called.

Results: There are totally 6 cases of DBS and 24 cases of DCC were enrolled. The laboratory data showed no significant differences (p-value>0.05), including AST, ALT, CRP, ALT/AST ratio, WBC, total bilirubin, alk-p, albumin, CEA, CA199,IgG 4 , and ratio of CA199/total bilirubin.

The diameter of maximum CBD and CHD also showed no significant differences (p-value>0.1). Interestingly,

the CBD gradient of DBS is 0.16±0.12 cm and the CBD gradient of DCC is 0.63± 0.41 cm (p-value=0.04). Besides, the patients with cholecystectomy showed 50% of DBS cases, which showed only 16.7% of DCC cases (p-value= 0.08).

Conclusions: First, CBD gradient might play a supportive role for us to distinguish between DBS and DCC, especially those with normal tumor markers, history of cholecystectomy, and positive IgG-4 level. Second, the percentage of cholecystectomy in DBS group showed higher than in DCC group, which might potentially play a predictor, even though the p-value didn’t meet the threshold.Third, the patients with high CBD gradient may have higher potential of DCC, and therefore further invasive procedure, such as diret per-oral cholangioscopy with tissue sampling, should be recommended.

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P.098

P.099

對於肝門周圍膽道癌的膽道引流緩和治療： 內視鏡與體表膽道引流之比較 BILIARY DRAINAGE FOR OBSTRUCTIVE JAUNDICE CAUSED

BY PALLIATIVE PERIHILAR CHOLANGIOCARCINOMA: THE ENDOSCOPIC VERSUS PERCUTANEOUS APPROACH

驗證體外震波碎石術對於膽結石功效之實 驗 THE EXPERIMENT TO VERIFY THE EFFECTIVENESS OF EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY FOR GALLBLADDER STONE 1,2

3

1,2

洪國棟 梁志明 邱逸群 郭仲謀 郭仲煌 盧龍生 吳鎭琨 張簡吉幸 高雄長庚紀念醫院

黃柏儒 陳汶吉 陳浤燿 1 中國醫藥大學附設醫院內科部 2 中國醫藥大學附設醫院內科部消化系 3 中國醫藥大學附設醫院泌尿部

Background: For palliative treatment of the obstructive jaundice associated with unresectable perihilar cholangiocarcinoma (PHC), percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde biliary drainage (ERBD) has been performed. Little is known about the better option for patients with obstructive jaundice caused by unresectable PHC. Aims: To compare the outcome of PTBD and ERBD in PHC patient with obstructive jaundice.

Methods: There are 46 patients who initial presented the jaundice and diagnosed as PHC between January 2013 and Dec 2018 in the cancer registry of Kaohsiung Chang Gung Memorial hospital. We excluded the patients who were resectable tumor (n=11), with previous history of hepatectomy (n=10), or without any treatment (n=4). Twenty one patients had received initial ERBD (n=14) or PTBD (n=7) for the palliative treatment of obstructive jaundice caused by palliative PHC. Successful clinical drainage, procedural complications, and the overall survival of patients were evaluated.

Results: The age, gender, infection of chronic hepatitis B or C, tumor stage or Bismuth type were similar between two groups. Univariate analysis revealed that the overall clinical successful drainage was higher in trend in the PTBD group (6/7, 85.7%) than in the ERBD group (8/14, 57.1%) (P=0.190); Longer survival time in the PTBD group (433.2 ±463.5 days) than in the ERBD group (151 ±133.1 days) (P< 0.001). However, the PTBD was easy to be dislodged (2/7= 28.6%). The complication rate was similar between PTBD group and ERBD group (Bleeding: 0% versus 7.1%, p=0.469, cholecystitis: 0% versus 7.1%, p=0.469, cholangitis: 0% versus 7.1%, p=0.469; pancreatitis :0% versus 14.3%, p=0.293.)

Conclusions: Besides ERBD, PTBD may be used as the initial treatment option to improve obstructive jaundice in patients with palliative PHC with less complications of endoscopy. However, PTBD was easy to be dislodged.

Larger scale clinical trials are necessary to clarify the safety and efficacy of PTBD.

Background: Nowadays, laparoscopic cholecystectomy is a standard treatment for patients with acute calculous cholecystitis. Extracorporeal shockwave lithotripsy (ESWL) is a procedure to remove stones in kidneys, and is it possible to use ESWL to remove gallstones as well? In 1997, Barkun et al. published the result of a randomized clinical trial for comparing the cost and effectiveness of laparoscopic cholecystectomy and ESWL to remove gallstones. Complete stone disappearance was achieved in only 38% of ESWL patients under using ursodeoxycholic acid for two years. (12 patients) This trial didn’t mention if the ESWL did break gallstones into small fragments or not. Besides, ursodeoxycholic acid is an active agent for dissolving cholesterol gallstones. So the result of this clinical trial might be due to the effect of ursodeoxycholic acid, but not ESWL. Aims: We use coarse salt and crystal sugar to simulate the gallstones in vitro and investigate if ESWL can make these two crystals into fragments in vitro.

Methods: The coarse salt and crystal sugar ( 0.5 x 0.5 and 1cm x 0.5cm) were placed into the 100ml of saturated sodium chloride and sucrose solution in transparent plastic bags, respectively, which was positioned in the shock focus. Thirty shocks at 17, 19, 21, and 24 kV were applied directly to the crystal and record the whole process by using a digital video camera and observed if the crystals were fragmented or not.

Results: The crystals were not broken after ESWL, and there was no different appearance of crystals after undergoing extracorporeal shockwave lithotripsy with every strength condition. These results were not comparable with those in the previous in vitro study, published in 1990 by Brink. J. A. et al. This might be because the crystals can move freely in the plastic bags, and the energy of extracorporeal shockwave was attenuated

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P.100 so that the crystals can’t be fragmented.

Conclusions: Using ESWL along to treat gallstones is a mission impossible. The results of this in vitro study can explain the low efficacy of treating gallstones by using ESWL. The rate of complete stone disappearance resulted from using ursodeoxycholic acid but no ESWL.

內視鏡逆行性膽胰管造影術後之胰臟炎的 風險因子 RISK FACTORS OF POST ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY PANCREATITIS (PEP) 1

1

1,2

1

1,2

1,2

何東翰 黃世斌 吳明順 冷國楓 粟發滿 連吉時 臺北市立萬芳醫院- 委託財團法人臺北醫學大學辦理, 1 內科部消化內科 2 臺北醫學大學醫學院醫學系內科部 Background: Post endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication and leading to prolong hospitalization following endoscopic retrograde cholangiopancreatography (ERCP). Until now, PEP remained a high morbidity and mortality during hospitalization after the procedure. Many risk factors had been identified to reduce the rate of PEP. However, the reported risk factors vary widely from different literatures.

In this retrospective study, we analyzed all the well-known risk factors that associate with PEP in our clinical cases.

Aims: To test the significant risk factors of PEP, so that endoscopists could pay more attention for the patients after ERCP. Methods: A total of 294 patients underwent therapeutic ERCP between October 2017 and November 2019 was included in this retrospective analysis. PEP was defined as typical pancreatic pain, elevated lipase or amylase level up to more than three times the upper limit of normal and/or image diagnosis with computed tomography after ERCP. Statistical analyses were performed to use IBM SPSS Statistics 22 and using a chi-square test and two-sided 5 % significance level.

Results: Prophylactic pancreatic stent insertion significantly associated with higher rate of PEP during ERCP (odds ratio 2.65; 95 % confidence interval 1.21 – 5.6; P = 0.01). The number needed to have harm (NNH) of PEP by prophylactic stent insertion was 6.12. Patient who had previous cholecystectomy showed mild but significant lower risk of PEP (P = 0.049) and large body mass index (BMI) revealed mild but significant higher risk of PEP (P=0.042).

Conclusions: In this retrospective study, we found that prophylactic pancreatic stent insertion significantly associated with higher rate of PEP, that might explain the debate between risk of pancreatitis and prophylactic

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P.101 pancreatic stent insertion. However, because this is a retrospective study of therapeutic ERCP, patients had repeated cannulation of pancreatic duct, prophylactic pancreatic stent was inserted at once. Further evaluation of pancreatic duct stent during therapeutic ERCP for prevention of PEP needs further investigation.

利用對比顯影內視鏡超音波診斷胰臟神經 內分泌瘤之特性：台中榮總之經驗 THE CHARACTERISTICS OF CONTRAST-ENHANCEMENT ENDOSCOPIC ULTRASOUND OF NEUROENDOCRINE PANCREATIC TUMORS: THE EXPERIENCE OF ONE SINGLE INSTITUTION FROM MIDDLE PART OF TAIWAN 1,3

1,2

1

1

廖思嘉 葉宏仁 廖苡君 林穎正 1 臺中榮民總醫院胃腸肝膽科 2 陽明大學 3 中國醫藥大學公衛所

Background: Neuroendocrine tumors of the pancreas (pNET) are less common than pancreatic ductal adenocarcinoma. Endoscopic ultrasound (EUS) is recommended as the method of choice for detection of very small pancreatic tumors. Contrast-enhanced endoscopic ultrasound (CE-EUS) is helpful in characterizing pancreatic tumors which are incidentally found on other imaging.

However, little known about how pNET in different grades present on CE-EUS. In our study, we used an ultrasound contrast agent (Sonazoid®) with microbubbles and investigated the characteristics of diagnosed pNET (particularly at an early stage) through CE-EUS by imaging the uptake of the microbubbles by the macrophages.

Aims: The objective of this study was to examine the characteristics of pNET on CE-EUS. Methods: We retrospectively analyzed the characteristics of CE-EUS of pNET confirmed by EUS-FNA or surgical pathology or 6-month follow up dynamic image our hospital between Dec. of 2018 to Dec. of 2019. Using an EUS device compatible with operations in the contrast harmonic mode, after B-mode observations, we intravenously administered 7.5 μl/kg of Sonazoid® and conducted longitudinal observations from an early stage, which included up to 180 seconds in the contrast mode. We investigated the changes in the pancreatic tumorous findings before the contrast enhancement and in the early (within 30s) and later phases (after 30s).

Results: During the study period, total 10 patients with image suspected pNET was enrolled. Among them, six patients were proved pNETs histologically. The sensitivity of the diagnoses of pNET in hypoechoic lesions using EUS (B-mode) were 60%. The sensitivity, specificity and accuracy of the diagnoses of pNET in hyper-enhanced lesions using CE-EUS were 83.3%, 75% and 80% respectively.

Conclusions: The CE-EUS for the diagnosis of pNET may be helpful. A hyperenhancing pattern could be used for the diagnosis of pNET.

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P.102

P.103

對於膽道困難插管的案例使用早期乳頭括 約肌預切開術有較高的成功率 EARLY PRECUT SPHINCTEROTOMY FOR DIFFICULT BILIARY ACCESS WITH HIGHER SUCCESSFUL RATE

經皮穿肝膽囊引流術治療急性膽囊炎的臨 床結果 - 單一醫學中心經驗 CLINICAL OUTCOME OF PERCUTANEOUS CHOLECYSTOSTOMY FOR ACUTE CHOLECYSTITIS - A SINGLE CENTER EXPERIENCE

盧龍生 梁志明 邱逸群 郭仲謀 郭仲煌 吳鎮琨 張簡吉幸 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 Background: There is scarce information on whether performing the early sphincterotomy rather than after several cannulation attempts is associated with different success and complication rates.

Aims: The aim of this retrospective study was is to compare the early sphincterotomy technique with the standard one in terms of the results and complications.

Methods: The precut sphincterotomy technique were including the performed using de-roofing needle-knife sphincterotomy (fistulotomy technique) or, only for patients with a small papilla, from the orifice, proceeding upwards in the 11 o’clock direction in 2–to 3-mm increments until the distal CBD was opened (conventional precut technique), or transpancreatic precut sphincterotomy (TPS) if three passes of the guidewire into the main pancreas duct (MPD). The early precut sphincterotomy was defined that the patients with unsuccessful CBD cannulation after 5 minutes or three passes of the guidewire into the MPD were assigned to early precut group (Group A). The others with prolonged cannulation attempts was assigned to non-early (Group B). The contemporary success rate and postoperative complications in 251 endoscopic retrograde cholangiopancreatography cases were frequently observed during the period from Sep 2017 to Dec 2019, and 139 of these cases with Naïve papilla were carried out with precut biliary sphincterotomy after the standard sphincterotomy had failed.

Results: The data from the 21 patients in the early precut group (Group A) and the 118 patients in the prolonged cannulation attempts group (Group B) were thus analyzed.

There were 60 cases performed with fistulotomy technique, 66 with conventional precut technique, 13 with TPS . There were no differences in the endoscopic complications of bleeding (0.0% vs. 3.4%, p=0.392), perforation (4.8% vs.

0.8%, p=0.165), and post ERCP pancreatitis (9.5% vs. 9.5%, p=0.995) between A and B group. The success rates of CBD cannulation were 90.5 % (19/21) and 69.5 % (82/118) in the group A and group B, respectively. The difference was significant (p=0.047).

Conclusions: Early precut sphincterotomy technique in a difficult biliary cannulation was safe and effective if performed by experienced endoscopists.

黃彥斌 徐友春 顏旭亨 陳洋源 彰化基督教醫院 Background: Acute cholecystitis is a common emergent disease. The current standard of treatment usually follows the 2018 Tokyo Guideline. Gall-bladder drainage is suggested for patients with moderate to severe acute cholecystitis. Delayed cholecystectomy should be performed for avoid recurrent acute cholecystitis. However, some patients, especially elder patients, hesitated for receive operation when the acute episode subsided.

Aims: To evaluate possible factors related to recurrent rate and mortality rate for patients who received percutaneous cholecystostomy for acute cholecystitis in our hospital.

Methods: All patients received percutaneous cholecystostomy for acute cholecystitis who admitted between January 1 to December 31 in 2018 were included.

Demographic characteristics, blood test, cholecystectomy rate, performance status, Charlson comorbidity index were retrieved from their medical records.

Results: Totally 133 patients were included. There are 25 patients (18.8%) received cholecystectomy within 2 months. There are 9 patients (6.8%) received cholecystectomy after 2 months. Recurrent rate were 26.3%(35/133) with including any event of recurrent cholecystitis, cholangitis or biliary pancreatitis. All-cause mortality was 18.0%(24/133) and biliary tract disease related mortality was 5.3%(7/133).

Conclusions: Among patients who received percutaneous cholecystostomy as initial treatment of acute cholecystitis, only 18.8% of the patients received cholecystectomy according to current practice guideline. Patient’s performance status and high Charlson comorbidity index were correlated to patient mortality.

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P.104 8 mm 無覆膜金屬支架在治療惡性肝門膽道 狹窄病人的臨床結果 CLINICAL OUTCOMES OF BILIARY STENTING WITH 8 MM UNCOVERED METAL STENTS IN THE PATIENTS WITH MALIGNANT HILAR BILIARY STRICTURES 黃文信 余承儒 何士奇 楊其穎 莊世杰 鄭幸弘 彭成元 林 俊哲 林肇堂 中國醫藥大學附設醫院內科部消化醫學中心 Background: Endoscopic biliary stenting has been well established as standard treatment of malignant biliary obstruction. Metal stents are more efficacious than plastic stents in unresectable malignant hilar biliary strictures.

Biliary stenting with metal stents has reported significant technical limitations when stents are deployed in sideby-side fashion. However, few reports are published to compare the size of metal stent in the treatment of malignant hilar biliary stricture.

Aims: To evaluate the clinical outcomes of 8 mm uncovered metal stents in the treatment of patients with malignant hilar biliary strictures.

Methods: Between February 2014 and December 2019, consecutive patients with malignant hilar biliary strictures undergoing ERCP with biliary stenting of 8 mm uncovered self-expanding metal stents (UCSEMS; Wallflex, Boston Scientific Inc., Marlborough, MA, USA) were retrospectively analyzed. Malignancy was diagnosed based on clinical, laboratory, imaging, and pathologic studies.

Results: A total of 38 patients (20 male and 18 female; mean age 68 years) with malignant hilar biliary strictures were included. Malignancy was pathologically proved in 33 (86.6%) of 38 patients. Majority (63%, 24/38) of hilar biliary malignancy was cholangiocarcinoma. Bismuth classification of the hilar malignancy was type I (n=13), II (n=4), IIIa (n=6), IIIb (n=2) and IV (n=13), respectively.

Before the metal stenting, fourteen patients (37%) and 26 patients (68%) received percutaneous drainage and biliary stenting with plastic stents. Twelve (33%) of 38 patients received chemotherapy and/or radiotherapy. Twenty-three patients underwent biliary stenting with one UCSEMS (Group 1) and fifteen patients with more than one UCSEMS (Group 2). The length of UCSEMS was 80 mm (n=14, 26.4%) and 100 mm (n=39, 73.6%). The lumen diameter of UCSEMS was all the same (8 mm). All patients underwent endoscopic sphincterotomy before metal stent placement.

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Length of strictures (average, 2.76±1.02 mm) was 2.59±1.21 mm and 3.03±0.59 mm in Group1 and Group 2, respectively. The technical success rate was 100% in both groups. However, Group 2 (80%) was better than Group 1 (69.6%) on clinical success rate (significant decrease in bilirubin level). The procedure time in Group 1 (26.1±9.8 (12-43) min) was shorter than Group 2 (46.5±14.5 (22-70) min) (P< 0.05). More patients in Group 2 (9/15, 69.2%) than Group 1 (3/23, 13%) had to undergo endoscopic balloon dilation during the procedures (P< 0.05). Early complications occurred in 4 (11%) of 38 patients and included cholangitis (n=3) and pancreatitis (n=1). During the period of follow-up, although stent patency, and stent complications were better in Group 1 than in Group 2, the differences were not statistically significant (P > 0.05).

Conclusions: For patients with malignant hilar biliary strictures, biliary stenting with one or more than one 8 mm UCSEMS is a feasible and safe procedure. Comparable stent patency and complications in the two groups.

2020 消化系聯合學術演講年會

P.105

P.106

經口內視鏡黏膜保存腫瘤切除術用於處理 上消化道黏膜下腫瘤 PERORAL ENDOSCOPIC TUMOR RESECTION WITH PRESERVED MUCOSA (POET-PM) TECHNIQUE FOR MANAGEMENT OF UPPER GASTROINTESTINAL TRACT SUBEPITHELIAL TUMORS

兒童食道閉鎖術後食道狹窄之處理 MANAGEMENT OF ANASTOMOTIC STRICTURE IN CHILDREN AFTER THE SURGICAL RECONSTRUCTION OF ESOPHAGEAL ATRESIA

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江承翰 曾柏鈞 陳冠至 吳建明 陳國鋅 林政錄 1 1 1, 3 李宗熙 林政寬 鍾承軒 1 亞東紀念醫院內科部肝膽腸胃內科 2 亞東紀念醫院外科部 3 臺灣輔仁大學

Background: Third space endoscopy technique facilitates therapeutic endoscopy in submucosal space.

Aims: This study aimed to investigate peroral endoscopic tumor resection with preserved mucosa (POET-PM) technique for treatment of upper gastrointestinal tract subepithelial Tumors (UGI-SETs).

Methods: Between February 2011 and September 2019, consecutive patients with SETs of esophagus, stomach and duodenum who underwent POET-PM for enlarging size during follow-up, malignant features or by patients’ requests were enrolled. Demographic, endoscopic and pathological data were analyzed retrospectively.

Results: Totally 14 esophageal, 24 gastric and 4 duodenal SETs were resected. The mean (±SD) age, gender ratio, endoscopic/pathological tumor size, complete resection rate, hospital stays, and mean procedure time of esophageal, gastric and duodenal SET patients were 53 (±3.13), 49.75 (±2.73), and 49.75 (±5.50) years old, female-to-male ratio of 35.71%, 54.17% and 0%, 12.36 (±9.89)/9.86 (±4.67), 12.17 (±5.55)/12.25 (±5.60), and 9.00 (±1.15)/7.50 (±1.00) mm, 92.9%, 87.5% and 75%, 4.14 (±0.21), 4.17 (±0.20), and 4.25 (±0.25) days, 13.86 (±6.05), 39.21 (±13.29), and 37.00 (±10.61) minutes, respectively.

The overall complicate rate was 26.2%, including 3 fever, 6 pain and 2 pneumoperitoneum with all self-limited. There was no mortality or recurrence reported with mean followup period of 23.74 (±4.12) months.

Conclusions: POET-PM is a safe and efficient third space endoscopic resection technique for UGI-SETs less than 20mm. Long term data are warranted to validate these results.

1,3

2

1

1

1

江哲銘 許文明 張美惠 許宏遠 倪衍玄 陳慧玲 1 吳嘉峯 1 國立臺灣大學醫學院附設醫院小兒部 2 國立臺灣大學醫學院附設醫院小兒外科 3 國防醫學院三軍總醫院小兒部

1

Background: Esophageal atresia is a congenital foregut anomaly. However, the anastomotic stricture after surgical reconstruction remains major morbidity even though the survival rate had improved a lot.

Aims: Our study aimed to evaluate the safety, effectiveness and long-term results of esophageal dilatation for children with anastomotic strictures after esophageal repair.

Methods: 40 children treated for EA in our hospital between January 2008 and December 2018 were included in this retrospective analysis. There were 16 patients who were diagnosed anastomotic stricture by barium esophagography or endoscopy and then received esophageal dilatation. The methods of esophageal dilatation including retrograde bougie dilator, controlled radial expansion (CRE) balloon catheter or Savary-Gilliard dilator. The therapeutic effect of esophageal dilatation was used weight-for-age z-score to evaluate the improvement of nutritional status.

Results: A total of 123 sessions of esophageal dilatation were performed in our 16 patients. The median session of the initial retrograde bougie dilator and CRE balloon catheter were 10 (3-17) and 3 (1-11) times per patient, respectively. No major complications occurred during or after the dilatation sessions. The weight-for-age z-score showed non-inferior increments in esophageal atresia children with anastomotic stricture receiving dilatation as compared with others after 6 months.

Conclusions: Esophageal dilatation provides a safe and effective mean of relieving anastomotic strictures with good nutritional improvement in children. Early diagnosis of anastomotic stricture is important for esophageal atresia patients following esophageal repair

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P.107

P.108

內視鏡超音波導引細針抽吸術的細胞學診 斷失敗因子分析 FACTORS AFFECTING CYTOLOGICAL RESULTS OF ENDOSCOPIC ULTRASOUND GUIDED-FINE NEEDLE ASPIRATION DURING LEARNING

對於口服 Aspirin 而發生消化性潰瘍出血 的患者，比較給予氫離子幫浦阻斷劑加上 Aspirin 或加上 Clopidogrel 兩種組合治療的 結果 THE IMPACT ON THE OUTCOME OF CONCOMITANT USERS OF PROTONPUMP INHIBITORS PLUS ASPIRIN OR CLOPIDOGREL IN PATIENTS WITH ASPIRIN-RELATED PEPTIC ULCER BLEEDING.

賴建翰 林慶忠 馬偕紀念醫院 Background: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a standard procedure used to obtain tissue samples for diagnosis of solid retroperitoneal tumours. However, this procedure demands high technical expertise and requires a strong learning curve.

Aims: Our aim was to identify factors associated with false-negative EUS-FNA results during the learning for endoscopists.

Methods: Our retrospective analysis was based on the EUS-FNA specimens collected by two novice endoscopists in 200 patients with retroperitoneal lesions who had confirmed image- or tissue-based diagnoses of malignancy or benign lesions.

Results: In the first 40 performances endoscopists , the false-negative diagnostic rate of EUS-FNA was higher among patients with chronic pancreatitis than in patients without chronic pancreatitis. Patients who underwent FNA through the trans-duodenal puncture route also had lower success cytological diagnosis rate than through the transgastric puncture route. The rate of successful cytological diagnoses with EUS-FNA improved after 40 procedures and was not influenced by chronic pancreatitis presentation or difference puncture route.

Conclusions: With regard to the learning curve, more than 40 procedures were required to achieve a stable success rate of EUS-FNA. Chronic pancreatitis and trans-duodenal puncture route are the predictive factors for a false-negative FNA cytological result during learning.

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1, 2

1

1

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楊世正 吳鎮琨 梁志明 李育騏 葉文碩 戴維震 1, 2 3 1, 2 吳耿良 許茜甯 蔡成枝 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院 3 長庚醫療財團法人高雄長庚紀念醫院藥劑部 Background: Currently, clopidogrel is commonly used for secondary cardiovascular event prevention in place of aspirin in patients who have experienced aspirinrelated upper gastrointestinal bleeding. However, protonpump inhibitors (PPIs) have been shown to decrease antiplatelet effects of clopidogrel, raising concerns about the cardiovascular safety of this drug combination.

As a consequence, the question of the PPI-clopidogrel interaction is still unresolved, and clinical consequences cannot be excluded.

Aims: To compare the rebleeding rate in patients with aspirin-related peptic ulcer bleeding after they were given PPI to treat peptic ulcer and concomitantly given either aspirin or clopidogrel for cardiovascular prevention in Taiwan.

Methods: n this population-based cohort study using the Taiwan National Health Insurance Research Database (NHIRD), all patients more than 20 years old who took aspirin for secondary cardiovascular prevention between January 1, 1997 and December 31, 2012 were considered for enrolment into the study. Concomitant use of antiplatelet other than aspirin before index date was excluded. The index date was defined as the discharge date of the main upper GI ulcer bleeding. Patients were followed up until censored or the end of the study period (December 31, 2012). Study subjects were allocated to two groups according to use of aspirin or clopidogrel. The primary end point of this study was the recurrence of peptic ulcer bleeding as the main diagnosis (the top three diagnoses) during hospitalization after index date. The secondary end point was the major adverse cardio-vascular events

2020 消化系聯合學術演講年會

P.109 (MACEs) and all-cause mortality. The two end points were analyzed respectively and independently. Adjustments for age, sex, concomitant medications, and comorbidity were performed for outcomes.

Results: From 3,236 patients discharged for aspirin-related peptic ulcer bleeding, we found 680 patients on aspirin plus PPIs and 306 patients on clopidogrel plus PPIs who met the selective inclusion criteria. Within 90 days, the incidences of recurrent peptic ulcer bleeding (4.26% vs. 4.9% in aspirin and clopidogrel groups, respectively) and MACEs (3.53 vs. 5.23%, respectively) were similar in both groups.

However, the clopidogrel group had a 4.49-fold death risk compared with the aspirin group at 90-day follow-up (95% CI = 1.54–13.14, p=0.006). Sub-analysis of the three components of MACEs showed that clopidogrel conferred higher incidence of acute myocardial infarction (2.61% vs. 0.44%, p=0.003), but no different risk of angina and stroke than that of aspirin. Multivariate logistic regression analysis showed that clopidogrel and age were independent predictors of all-cause mortality.

Conclusions: Among aspirin users for secondary cardiovascular event prevention experiencing with peptic ulcer bleeding, continuation of aspirin or shifting to clopidogrel is not associated with an increased risk of recurrent bleeding or incident MACEs. However, using clopidogrel plus PPIs was associated with higher rates of acute myocardial infarction and mortality than aspirin plus PPIs. The real-world evidence raises the need to re-assess the current therapeutic options in secondary cardiovascular prevention applying aspirin vs. clopidogrel combining PPIs for peptic ulcer bleeding patients.

經皮內視鏡胃造廔術 VS 鼻胃管餵食：口咽 吞嚥障礙增加肺炎需要住院風險 PERCUTANEOUS ENDOSCOPIC GASTROSTOMY VERSUS NASOGASTRIC TUBE FEEDING: OROPHARYNGEAL DYSPHAGIA INCREASES RISK FOR PNEUMONIA REQUIRING HOSPITAL ADMISSION 張維國 黃信閎 林煊淮 施宇隆 謝財源 三軍總醫院腸胃科 Background: Aspiration pneumonia is the most common cause of death in patients with percutaneous endoscopic gastrostomy (PEG) and nasogastric tube (NGT) feeding.

Current guidelines recommended PEG for long-term and NGT for short-term enteral nutrition. However, patients are commonly placed on NGT for long-term enteral feeding in Asian countries.

Aims: We aimed to evaluate the severity of oropharyngeal dysphagia and to follow-up with patients on NGT feeding who required hospital admission for pneumonia and, ultimately, to stratify the risk of pneumonia in patients on NGT feeding.

Methods: Oropharyngeal dysphagia was stratified by endoscopic observation of the pooling secretions in the pharyngolaryngeal region: control group (<25% pooling secretions filling the pyriform sinus), pharyngeal group (25%-100% pooling secretions filling the pyriform sinus), and laryngeal group (pooling secretions entering the laryngeal vestibule). Demographic data, swallowing level scale score, and pneumonia requiring hospital admission were recorded Results: Patients with NGT (n = 97) had a significantly higher incidence of pneumonia (episodes/person-years) than those patients with PEG (n = 130) in the pharyngeal group (3.6 ± 1.0 vs. 2.3 ± 2.1, P < 0.001) and the laryngeal group (3.8 ± 0.5 vs. 2.3 ± 2.2 vs, P < 0.001). The risk of pneumonia was significantly higher in patients with NGT than in patients with PEG (adjusted hazard ratio = 2.85, 95% CI: 1.46-4.98, P < 0.001). Cumulative proportion of pneumonia was significantly higher in patients with NGT than with PEG for patients with oropharyngeal dysphagia (pharyngeal + laryngeal groups) (P = 0.035) Conclusions: PEG is a better choice for long-term tube feeding compared to NGT due to the decreased risk for developing pneumonia requiring hospital admission, especially for patients with oropharyngeal dysphagia. These findings are useful in the development of clinical guidelines and to inform discussions among health care provider, patients, and family members with regards to long-term feeding method.

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P.110 在內視鏡輔佐下可提高高解析度食道動力 學檢查的完成度 ENDOSCOPY ASSISTED CATHETER INSERTION CAN INCREASE HIGH RESOLUTION ESOPHAGEAL MANOMETRY COMPLETENESS 宋寬益 王彥博 盧俊良 臺北榮民總醫院 Background: Esophageal high resolution manometry(HRM) is widely used for esophageal motility evaluation in clinical practice. According to Chicago’s criteria version 3.0, 10 consecutive wet swallowing of 5 ml water in the supine position is needed for evaluation.

However, about 21% of HRM studies are imperfect (S. Roman et al. CGH 2001;9(12):1050-1055). In patients with large hiatal hernia and achalasia, catheter occasionally can’t transverse esophageal-gastric junction. Using endoscopy to guide and assist high resolution manometry may can help HRM catheter insertion.

Aims: we evaluate the efficacy of endoscopy assisted catheter insertion in performing HRM exams.

Methods: We reviewed the data from a prospectively recorded functional esophageal disease database in endoscopy center of Taipei Veterans General Hospital.

Records of consecutive patients who received HRM exams from June, 2017 to October, 2019 are analyzed. HRM was performed with 32 circumferential pressure channels with 16 impedance channels solid-state catheter (Medical Measurement Systems, Netherlands) and analyzed according to Chicago classification of esophageal motility disorders version 3.0. For patients failed manual catheter insertion or intolerance to catheter insertion, endoscopy guided probe insertion was performed. Snare assisted HRM catheter insertion was used in difficult cases.

Results: Total 192 patients received 207 times of HRM exams in the study period. The patient’s average age was 53.91 years old. 183 HRM exams (88.4%) can be performed conventionally. 20 patients received 23 times of HRM catheter insertion with endoscopic assistance, and all of them completed HRM exams successfully. 18 patients (90%) were diagnosed with achalasia, while 1 patient had large diverticulum and 1 had large hiatal hernia.

Only 1 patient didn’t complete HRM exam due to rhinitis inducing nasal obstruction. With endoscopic assistance, the completeness of HRM exams increased from 88.4% to 99.5% .(p<0.01). No clinical significant adverse events or

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HRM probe damage were noted in the study period.

Conclusions: In patients with difficult HRM catheter insertion, endoscopy assisted catheter insertion is highly effective. Endoscopy assisted catheter insertion can increase high resolution esophageal manometry completeness without side effects.

2020 消化系聯合學術演講年會

P.111

P.112

內視鏡黏膜下切除術與亞全胃切除手術在 早期胃癌治療之比較 ENDOSCOPIC SUBMUCOSAL DISSECTION COMPARING WITH SURGICAL RESECTION IN PATIENTS WITH EARLY GASTRIC CANCER – A SINGLE CENTER EXPERIENCE IN TAIWAN

由病例對照研究探討血清 CA 72-4 與胃疾病 的關聯性 THE CORRELATION BETWEEN THE ETIOLOGIES AND SERUM CA 72-4 IN GASTRIC DISORDERS-A CASE CONTROL STUDY

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洪子瞻 劉志銘 葉啟娟 顏宏軒 吳明賢 賴逸儒 1 陳建全 1 國立臺灣大學醫學院附設醫院內科部 2 國立臺灣大學醫學院附設醫院外科部

Background: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan.

Aims: This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment.

Methods: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan.

The primary endpoint was disease specific survival.

Recurrence free survival and length of hospital stay were also compared.

Results: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p=0.39), so as the recurrence free survival (cumulative survival 92.31% vs.

94.06%, p=0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs.

40%, p<0.01). However, the shorter duration of hospital stay in ESD was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p<0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery.

Conclusions: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pretreatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

1,2

1

1

1,2

陳銘仁 章振旺 洪建源 林揚笙 1 馬偕紀念醫院胃腸肝膽科 2 馬偕紀念醫院

Background: The clinical application of CA 72-4 in gastric cancer, showing a sensitivity of approximately 30% in and with an overall specificity of more than 95% that seldom increased in normal population.

Aims: This aim is to find the etiologies and factors contribute the CA 72-4 in gastric disorders from a case control and cohort studies.

Methods: For assessing the correlation between the level of Ca 72-4 and gastric associated disorders, 592 health peoples scheduled for health evaluation were retrospective analyzed. The health evaluation package includes EGD and serum tumor markers including Ca 72-4. These endoscopic characteristics were evaluated with the level of serum Ca 72-4 level.

Results: In the retrospective analyses of 592 peoples, 117 people had an elevated Ca 72-4, and 475 people had a normal level. The mean age of elevated Ca 72-4 people was 43.3 ± 12.0 and the male gender was 59.8 %. The percentage of GU or DU in the elevated Ca 72-4 group was 30.8 and 9.8 % and the percentage of erosive esophagitis was 27.3%. The percentage of gastric polyps was 16.2%.

Multivariate linear regression analysis was performed to determine factors associated with the Ca 72-4 level in the case control study. The determined factors for the Ca 72-4 level are, gastric ulcer (odds ratio [OR], 2.70 (2.271 to 14.332), p = 0.007) and erosive esophagitis (odds ratio [OR], 2.09 (0.3993 to 12.218), p = 0.036).

Conclusions: We assumed that some intestinal metaplasia with elevation of CA 72-4 might benefit directly from gastric ulcer or erosive esophagitis. Though CA 72-4 was not recommended for screening, but the false positive might point high probability of 79/117 (66.6 %) for benign gastric disorder that deserved further evaluation and treatment.

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2020 消化系聯合學術演講年會

P.113 比 較 L- 薄 荷 醇 (L-menthol) 與 補 斯 可 胖 (Buscopan) 對年長患者接受上消化道內視 鏡檢查之抗蠕動效果與安全性 COMPARISON OF ANTIPERISTALTIC EFFECT AND SAFETY BETWEEN L-MENTHOL AND BUSCOPAN DURING UPPER GI ENDOSCOPY IN THE ELDERLY 1,2

2,3

2,3

1,2

楊宗杰 陳炳憲 王彥博 黃怡翔 侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院內視鏡診斷暨治療中心

1,2

Background: Hyoscine-N-Butylbromide (Buscopan) is the most commonly used medication for anti-peristalsis during upper GI endoscopy. However, almost 50% elderly patients have contraindications to Buscopan. Survey for alternative medication is needed.

Aims: The aim of this study is to compare the antiperistaltic effect and safety between L-menthol and Buscopan in the elderly who receive upper GI endoscopy.

Methods: This is a prospective, randomized, doubleblind study. The elderly (>65 y/o) without contraindication to Buscopan, going to receive non-sedative upper GI endoscopy were enrolled and randomized into L-menthol group and Buscopan group. In L-menthol group, the patients received 1ml normal saline intravenous injection and 20ml 0.8% L-menthol sprayed on the gastric antrum during endoscopy. In Buscopan group, the patients received 1ml Buscopan intravenous injection and 20ml placebo sprayed on the gastric antrum during endoscopy.

The primary outcome was change of peristaltic grade before and after medication. The secondary outcome was adverse events, hemodynamic change, difficulty grade of performing endoscopy and satisfactory of patients.

Results: From September 2011 to November 2012, 39 elderly patients going to receive non-sedative upper GI endoscopy were screened. Twenty (51.2%) of them without contraindication to Buscopan were enrolled and randomized into L-menthol group (n=10) and Buscopan group (n=10).

Compared with before medication, both groups showed significant peristaltic grade improvement after medication (L-menthol: p=0.005; Buscopan: p=0.004). There was no difference in peristaltic grade before medication and after medication between two groups. There was significantly higher systolic blood pressure, diastolic blood pressure and faster heart rate after Buscopan injection, but only higher

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systolic blood pressure after L-menthol spray. The other adverse events, difficulty grade of performing endoscopy and satisfactory of patients were similar between two groups.

Conclusions: L-menthol is a safe and effective alternative antispasmodic medication with fewer side effects compared with Buscopan in elderly patients undergoing upper GI endoscopy.

2020 消化系聯合學術演講年會

P.114 內視鏡食道環狀肌肉切開術 -- 在一醫學中 心的 46 例經驗 PERORAL ENDOSCOPIC MYOTOMY — FORTY-SIX CASES EXPERIENCE IN A MEDICAL CENTER 1,4,5

3,4,5

1,4,5

謝子鈺 胡亭宇 陳銘仁 1 臺北馬偕醫院胃腸肝膽科 2 臺東馬偕醫院胃腸肝膽科 3 臺北馬偕醫院重症醫學科 4 馬偕醫護管理專科學校 5 馬偕醫學院

白明忠

2,4,5

Background: Achalasia is a primary motor disorder of the esophagus characterized by loss of enteric neurons leading to absence of peristalsis and impaired relaxation of the lower esophageal sphincter. Three distinct subtypes of achalasia (types I, II, and III) are defined with highresolution manometry (HRM) that have both prognostic and potential therapeutic implications. Current treatment including medicine, pneumatic dilatation, Heller myotomy.

Peroral endoscopy myotomy (POEM) is a minimal invasive treatment for esophageal achalasia, and become more and more popular in recent years.

Aims: To evaluate the efficacy of POEM and compared this treatment result in type I and type II achalasia.

Methods: From April 2014 to December 2019, there are total 44 patients with achalasia, and underwent 46 POEM in Mackay Memorial Hospital. We use Eckardt score to grade the four major symptoms of achalasia (including weight loss, dysphagia, chest pain, and acid regurgitation).

All patients have esophagogram and Chest CT before treatment. Twenty-three patients (11 patients type I achalasia, and 12 patients type II achalasia) were examined for HRM and timed barium esophagogram before and after POEM. Results: Forty-four patients underwent 46 POEMs between April 2014 and December 2019. The mean age was 44.6 years old (16-79 y/o). The mean duration of patients’ symptoms was 48.9 months (1-600 months). The length of POEM was 8.8 cm (6-14 cm), and the mean operating time was 90 minutes (43-267 min.). The median hospital stay was 4.9 days (3-10 days). All patients had relief of dysphagia [dysphagia score ≤ 1] three months after POEM. The mean Eckardt score pre-POEM and post-POEM are 6.7 and 0.2, respectively.

In the 23 patients who had HRM report (11 patients type I achalasia, and 12 patients type II achalasia), the mean

LES resting pressure before and after POEM were 34.6 mmHg (15-61 mmHg) and 15.4 mmHg (3.4-34 mmHg), respectively. The mean integrated relaxation pressure-4s (IRP-4s) was 17.6 mmHg (5.1-25 mmHg) before POEM, and 8.4 mmHg (1.5-17.3 mmHg) after POEM. Type II achalasia patients had higher mean LES resting pressure than type I patients (40.9 vs 28.9 mmHg, p= 0.026). Before POEM, type II patients also had higher IRP-4s than type I patients (28.8 vs 17.6 mmHg, p= 0.021). Type I patients had higher pain score on the operation day than type II patients (4.9 vs 2.6, p= 0.033). Three months after POEM, type II patients had lower Eckardt score type type I patients (0 vs 0.3, p= 0.046).

Conclusions: POEM is a safe and reliable treatment for achalasia. HRM is the standard for diagnosing and classifying achalasia, and is import for predicting the prognosis of POEM.

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2020 消化系聯合學術演講年會

P.115 對於高風險性消化性潰瘍出血在蒸餾水注 射術後，比較併用氬氣電漿凝固術或止血夾 兩者之止血療效 ENDOSCOPIC INJECTION PLUS ARGON PLASMA COAGULATION COMPARED TO ENDOSCOPIC INJECTION PLUS HEMOCLIPPING FOR HIGH-RISK PEPTIC ULCER BLEEDING 1

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1

1

2

王惠民 許秉毅 蔡峯偉 陳文誌 彭南靖 1 高雄榮民總醫院胃腸肝膽科 2 高雄榮民總醫院核醫部

Background: Endoscopic treatment is recommended for initial hemostasis in high-risk peptic ulcer hemorrhage.

Many endoscopic devices have been demonstrated to be effective in the hemostasis of bleeding ulcers.

Aims: Nevertheless, the additional hemostatic efficacy of argon plasma coagulation (APC) after endoscopic injection therapy has not been widely investigated. Our study group conducted a randomized trial of APC plus injection therapy versus clipping plus injection therapy for high-risk peptic ulcer bleeding.

Methods: From Feb. 2012 to Feb. 2016, consecutive patients with high-risk bleeding ulcers, characterized by active bleeding, non-bleeding visible vessels and adherent clots, were admitted to our hospital. They prospectively randomly received either APC therapy plus distilled water injection or hemoclipping plus distilled water injection.

Intravenous Pantoprazole administration was conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer healing. Episodes of rebleeding were repeatedly treated with endoscopic combination therapy. Patients who did not benefit from retreatment underwent arterial embolization or emergency surgery.

Results: In all, 161 eligible patients were analyzed.

Hemostatic efficacy in 80 patients treated with APC plus distilled water injection (APC group) was prospectively compared with 81 patients treated with hemoclipping plus distilled water injection (Hemoclip group). The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 79 patients treated with APC combined with injection therapy, and 78 patients with hemoclipping plus distilled water injection therapy (98.8% vs. 97.5%, P = 0.620). Bleeding recurred in 3 patients in the APC group, and in 4 patients in the Hemoclip group (3.8% vs. 4.9%, P = 1.000). No significant differences were observed between the 2 study

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groups in hospital stay, transfusion requirements, surgery/ arterial embolization and mortality.

Conclusions: Endoscopic therapy with APC plus distilled water injection is similarly effective as hemoclipping plus distilled water injection for preventing rebleeding in the management of high-risk bleeding ulcers. Both treatment methods also have similar safety during therapeutic endoscopy.

2020 消化系聯合學術演講年會

P.116 糖尿病患者胃排空時間與臨床症狀表現之 相關性 INVESTIGATION OF GASTRIC EMPTYING AND UPPER GASTROINTESTINAL MANIFESTATION AMONG PATIENTS WITH DIABETES MELLITUS 1,5

1,2,3

1,2,3

4,5

4,5

詹宜學 章振旺 陳銘仁 曾屏輝 吳明賢 1 馬偕紀念醫院胃腸肝膽內科 2 馬偕醫護管理學院 3 馬偕醫學院 4 臺大醫院內科部 5 臺大醫學院臨床醫學研究所

Background: The patient who have diabetes mellitus with poor control usually suffered from many complications such as retinopathy, neuropathy and cardiovascular disease.

Gastrointestinal symptoms like abdominal fullness, gastroesophageal reflux disease, constipation and diarrhea had high occurance rates in patient with poor sugar control.

Gastroparesis is a chronic syndrome caused by delayed gastric emptying in the absence of mechanical obstruction and is accompanied by symptoms such as post prandial fullness, bloating, nausea, vomiting and easy satiety.

Aims: Therefore, we arranged gastric emptying scintigraphy for the people with diabetes mellitus.

We discuss association of gastric emptying time and gastrointestinal manifestations among people with diabetes mellitus.

Methods: The patient has history of diabetes mellitus.

The patients suffered from upper gastrointestinal symptom who visited to our gastrointestinal outpatient clinic. We arranged ultrasonography and upper gastrointestinal endoscopy examination. Past medical and family history are collected. Blood examination such as fasting glucose, HbA1C, cholesterol and triglyceride are collected. We arrange gastric emptying scintigraphy for the patients who had done endoscopy examination and still suffered from upper gastrointestinal symptom even received treatment.

The patients collected from January 2017 to February 2019.

This is a single center retrospective study.

Results: Total seven patients exclude from the study. One patient do not arranged upper endoscopy examination. Four patients upper endoscopy reveal peptic ulcer disease. One patient suffered from GERD for long times and received fundoplication surgery. One patient is obesity and post bariatric surgery. There are twenty eight patients include

in the study. Thirteen patients are not diabetes mellitus patients. One of the patient without DM have delayed gastric emptying time. Twelve patients have normal gastric emptying time. Fifteen patients have diabetes mellitus.

Four of the patient with DM have delayed gastric emptying time. Two of the DM patients have rapid gastric emptying time. The other patients with DM have normal gastric emptying time.

Conclusions: he patients with diabetes mellitus under poor control may suffered delayed gastric emptying.

Some diabetes also have rapid gastric emptying. However, the clinical symptoms among delayed and rapid gastric emptying are not different. We assumed that diabetes neuropathy may affect not only motor neuron but also sensor neuron. The relations between gastric emptying (rapid and delayed), sugar control and clinical symptom are still not clear, which need more cases and studies to discuss.

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2020 消化系聯合學術演講年會

P.117 巴瑞特食道症、輕度（洛杉磯分類 A/B 級） 腐蝕性食道炎、重度（洛杉磯分類 C/D 級） 腐蝕性食道炎患者臨床特質之比較 COMPARISON OF THE CLINICAL CHARACTERISTICS OF THE PATIENTS WITH BARRETT’S ESOPHAGITIS, MILD (LOS ANGELES GRADE A/B) AND SEVERE (LOS ANGELES GRADE C/D) EROSIVE ESOPHAGITIS 1

2

3

4

5

1

吳奕霆 吳登強 高崧碩 蔡成枝 盧俊良 許秉毅 1 中國醫藥大學安南醫院消化內科 2 高雄醫學大學內科部胃腸肝膽科 3 高雄榮民總醫院內科部胃腸肝膽科 4 高雄長庚醫院內科部胃腸肝膽科 5 臺北榮民總醫院內科部胃腸肝膽科

Background: Gastroesophageal reflux disease is the most common gastrointestinal diagnosis recorded during visits to outpatient clinics. It is a wide spectrum of disorders including non-erosive reflux disease, erosive esophagitis and Barrett’s esophagus.

Aims: To compare the clinical characteristics of gastroesophageal reflux disease patients with Barrett’s esophagitis, mild (Los Angeles grade A/B) and severe (Los Angeles grade C/D) erosive esophagitis.

Methods: Consecutive adult patients with endoscopic findings of mild (Los Angeles grade A/B) erosive esophagitis, severe (Los Angeles grade C/D) erosive esophagitis or Barrett’s esophagus were recruited for this study and prospectively assessed their clinical characteristics. Patients were requested to complete a validated questionnaire (Chinese GERDQ). A complete medical history and demographic data were obtained from each patient, including age, sex, medical history, history of smoking, alcohol, coffee and tea consumption, duration, frequency and severity of reflux symptoms. Additionally, a body mass index was checked, and gastric biopsy was performed for H pylori examination. Finally, the clinical characteristics of the patients with Barrett’s esophagitis, mild (Los Angeles grade A/B) and severe (Los Angeles grade C/D) erosive esophagitis were compared.

Results: A total of 295 patients with Los Angeles grade A/ B erosive esophagitis, 44 patients with Los Angeles grade C/D erosive esophagitis and 246 patients with Barrett’s esophagus were recruited for the study. Compared with Los Angeles grade A/B erosive esophagitis patients, those with Los Angeles grade C/D erosive esophagitis were older (P

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< 0.001) and had higher frequencies of male gender (P = 0.010), underlying disease (P < 0.001), hiatal hernia (P < 0.001) and proton pump inhibitor dependence (P < 0.001).

However, they had lower frequencies of acid regurgitation (P = 0.018) and epigastric acidity (< 0.001) than patients with Los Angeles grade A/B erosive esophagitis. Barrett’s esophagitis patients were older (P = 0.001) and had higher frequencies of male gender (P = 0.003), hiatal hernia (P = 0.020) and proton pump inhibitor dependence (P < 0.001) compare with those with Los Angeles grade A/ B erosive esophagitis. However, the former had lower frequencies of smoking (0.002), H pylori infection (0.012), acid regurgitation (P < 0.001), heartburn (P < 0.001) and epigastric acidity (< 0.001) than the latter.

Conclusions: Patients with Los Angeles grade C/D erosive esophagitis and Barrett’s esophagus have different clinical characteristics than those with Los Angeles grade A/B erosive esophagitis.

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洛杉磯分類 A/B 級腐蝕性食道炎患者症狀 復發之危險因子 RISK FACTORS FOR SYMPTOM RELAPSE IN PATIENTS WITH LOS ANGELES GRADE A/B EROSIVE ESOPHAGITIS

診斷性上消化道內視鏡檢查發現十二指腸 白點的臨床意義 CLINICAL SIGNIFICANCE OF DUODENAL WHITE SPOTS INCIDENTALLY FOUND DURING UPPER GASTROINTESTINAL ENDOSCOPY

施長碧 吳登強 陳彥樺 蔡成枝 盧俊良 許秉毅 1

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中國醫藥大學安南醫院消化內科 2 高雄醫學大學內科部胃腸肝膽科 3 高雄榮民總醫院內科部胃腸肝膽科 4 高雄長庚醫院內科部胃腸肝膽科 5 臺北榮民總醫院內科部胃腸肝膽科

Background: Gastroesophageal reflux disease (GERD) is a common problem in both primary and secondary care settings. Up to 50–90% of GERD patients experience symptom recurrence within 6 months following completion of initial treatment.

Aims: To search the risk factors for symptom relapse in patients with Los Angelus Grade A/B erosive esophagitis.

Methods: Patients with Los Angeles Grade A/B erosive esophagitis were randomly treated by esomeprazole 40 mg qd for either 4 or 8 weeks. Those who had complete symptom resolution after initial treatment were recruited for this study. Their reflux symptoms were regularly followed up for 3 months following initial therapy, and the risk factors for symptom relapse within 3 months were analyzed by univariate and multivariate analysis.

Results: 289 Los Angeles Grade A/B erosive esophagitis patients with complete symptom resolution following initial treatment were recruited. Univariate analysis showed that old age (P < 0.001), severity of erosive esophagitis (P = 0.037), treatment duration (P = 0.003), alcohol drinking (0.007), and spicy food consumption (P = 0.019) were factors related symptom relapse. Multivariate analysis revealed that old age and erosive esophagitis Los Angeles Grade B were independent risk factors for symptom relapse with odds ratios of 2.98 (95% confidence interval [CI]: 1.64 – 5.43) and 1.80 (95% CI: 1.06 – 3.06), respectively. Habit of alcohol drinking and 8-week proton pump inhibitor therapy were independent protective factors with odds ratios of 0.56 (95% CI: 0.32-0.99) and 0.49 (95% CI: 0.29-0.81), respectively.

Conclusions: Prolong proton pump inhibitor treatment duration from 4 weeks to 8 weeks can decrease the relapse of Los Angeles Grade A/B erosive esophagitis. The reason why habit of alcohol drinking on recruitment is a protective factor for symptom relapse in patients with mild erosive esophagitis deserves further investigations.

黃彼得 林連福 吳明駿 童綜合醫療社團法人童綜合醫院 Background: Duodenal white spots are occasionally encountered during routine upper gastrointestinal endoscopy with a reported prevalence of 3.2-4.8% and often identified as intestinal lymphangiectasia. The duodenal white spots can present as (1) scattered pinpoint white spots, (2) diffuse whitish villi and (3) focal small whitish macules or nodules. When biopsied, milky fluid can often be seen draining from the lesions. However, duodenal white spots could represent a spectrum of pathologies other than lymphangiectasia. Biyikoglu et al reported that duodenal white spots have heterogeneous etiologies: 36.4% intestinal lymphangiectasia, 28.1% chronic duodenitis, and 14% giardiasis.

Aims: The aim of this study was to evaluate the clinical significance of duodenal white spots incidentally found during diagnostic upper gastrointestinal endoscopy.

Methods: From Nov 2017 to Oct 2019, patients undergoing diagnostic upper gastrointestinal endoscopy were prospectively studied for the presence of duodenal white spots. Biopsies were taken for histological examination and clinical data collected for evaluation.

Results: A total of 12 patients (8 males, 4 females) with average age of 60.4 years (range 32-89) were enrolled in this study. All were H. pylori negative except for one patient. Epigastric pain was the most common symptom, followed by acid regurgitation and epigastric fullness.

Associated medical condition included DM (3), tuberculosis (1) and colon cancer (1). Histological examination revealed the following pathologies: lymphangiectasia (4), hyperplastic change (3), lymphoid hyperplasia (2), chronic duodenitis (1), follicular lymphoma (1) and metastatic adenocarcinoma (1).

Conclusions: Duodenal white spots encountered during upper gastrointestinal endoscopy procedure must be evaluated carefully. Histopathological examination may be necessary for differential diagnosis and determination of etiologic factor.

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優碘塗抹於胃造廔管壁在減少經皮內視鏡 胃造廔術後造口感染的效益 EFFECTIVENESS OF BETADINECOATING GASTROSTOMY TUBE IN REDUCING PERISTOMAL INFECTION AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMY

使用高解析度食道壓力併阻抗檢測探討對 質子幫浦抑制劑治療反應不佳之胃食道逆 流症狀之患者食道蠕動功能 ESOPHAGEAL MOTILITY IN PATIENTS WITH PROTON-PUMP INHIBITOR REFRACTORY GASTROESOPHAGEAL REFLUX SYMPTOMS: A STUDY BASED ON HIGH-RESOLUTION IMPEDANCE MANOMETRY

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陳宥任 楊宗杰 侯明志 1 臺北榮民總醫院內科部腸胃科 2 國立陽明大學醫學院 Background: Pull method is the most widely used technique of percutaneous endoscopic gastrostomy (PEG) because of simplicity. However, peristomal infection is a significant common complication.

Aims: Our study tried to figure out if Betadine-coating gastrostomy tube could prevent the occurrence of peristomal infection.

Methods: This is a prospective randomized controlled trial. Consecutive patients undergoing PEG placement were randomized to two groups, including group 1 (gastrostomy tube coated with Betadine) and group 0 (gastrostomy tube did not coated with Betadine). For each patient, the peristomal area was evaluated daily for 2 weeks after PEG placement. The presence of erythema and of exudate were scored on a scale of 0 to 4; induration was scored on a scale of 0 to 3. Criteria for infection were a maximum combined score of 8 or higher, or the presence of suppurating exudate.

Results: From January 2014 to December 2019, total 44 patients were included and randomized to 21 patients in group 1 and 23 patients in group 0. There was no significant difference between two groups with respect to clinical characteristics and underlying disease. There was no significant difference on peristomal infection, aspiration pneumonia and leakage between group 1 and group 0.

However, CRP elevation before and after PEG placement was significantly lower in group 1 (3.29 VS. 1.87, P=0.04).

Moreover, the ROC curve of CRP elevation could predict peristomal infection(AUC 0.79, P=0.006; cuff off value 2.94, sensitivity 0.8, specificity 0. 806).

Conclusions: Gastrostomy tube coated with Betadine could reduce CRP elevation after PEG placement. CRP elevation could predict peristomal infection. However, there was no significant difference on peristomal infection rate. Wound care skill might be the reason which influence the final outcome.

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曾屏輝 吳嘉峰 王秀伯 吳明賢 陳建全 1 臺大醫院內科部 2 臺大醫院小兒部

Background: Refractory gastroesophageal reflux disease (GERD) symptoms despite standard proton-pump inhibitor (PPI) treatment are increasingly common in clinical practice. The underlying pathophysiology is complex and poorly understood.

Aims: We aimed to investigate the esophageal motility in patients with PPI-refractory symptoms.with the novel highresolution impedance manometry (HRIM).

Methods: From November 2014 to August 2019, consecutive patients with persistent gastroesophageal reflux symptoms despite PPI treatment for at least 8 weeks were prospectively enrolled. All subjects filled out standard questionnaires for GERD severity and frequency.

Esophageal motility was evaluated with HRIM and updated Chicago Classification. The reflux profile was evaluated with 24-h multichannel intraluminal (MII)-pH monitoring.

Results: A total of 130 patients with refractory symptoms were analyzed. The mean age (range) was 50.3(18-79).

Fifty-four (41.5%) were male. Erosive esophagitis was found in 48 (36.9%) and most were mild in severity.

The most common esophageal motility abnormalities on HRIM were ineffective esophageal motility (n=51, 39.2%), followed by absent contractility (n=7, 5.4%), and esophagogastric junction outflow obstruction (n=5, 3.8%).

Two patients were diagnosed with achalasia. Hiatal hernia was found in 26 patients (20%). Eighteen (13.8%) patients were found to have abnormal bolus transit (incomplete bolus transit in 30% or more swallows). Sixty-five (50%) patients had normal HRIM results. However, symptom profiles were similar between those with and without esophageal dysmotility. Sixty-four patients were studied ‘off’ and 66 patients ‘on’ PPI during MII-pH monitoring and 73 patients were diagnosed with functional heartburn accordingly. There was no significant difference of various

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P.122 HRIM parameters between patients with and without functional heartburn.

Conclusions: Based on HRIM, we have found a high prevalence of esophageal motility abnormalities, notably esophageal hypocontractility, in Taiwanese patients with PPI-refractory GERD symptoms. Whether add-on therapy with prokinetic agents could help to improve the treatment response in this group of patients deserve further studies.

運用高解析阻抗壓力測量儀評估咽喉吞嚥 功能：單一中心之經驗

HIGH RESOLUTION IMPEDANCE MANOMETRY FOR EVALUATING PHARYNGEAL SWALLOWING: A SINGLE CENTER EXPERIENCE 梁書瑋 洪睿勝 翁銘彣 雷尉毅 劉作財 易志勳 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: High resolution impedance manometry (HRIM) provides comprehensive information of esophageal motility. The application of HRIM in pharyngeal dysmotility allows measure biomechanical features of the pharynx that may be related to dysphagia symptoms and aspiration risks. We have previously demonstrated that HRIM provides information of not only pressure topography but also pressure-flow analysis.

Aims: The aim of this study was to demonstrate the experience in patients with suspected pharyngeal dysmotility and the controls.

Methods: We collected data from one patient with amyotrophic lateral sclerosis, one with achalasia and one control. Participants received symptom screening with Brief Esophageal Dysphagia Questionnaire (BEDQ).

HRIM system (Laborie, Solar GI acquisition unit, Medical Measurement Systems and solid-state catheter, K83259-E1263-D) and standardized bolus media (IDDSI levael 0 and IDDSI level 4; Trisco, Precise SBMkit) were used. Metrics of each swallow include hypopharyngeal intra-bolus pressure at 1 cm above upper esophageal sphincter (IBP), upper esophageal sphincter bolus presence time (BPT), Mean hypopharyngeal peak pressure (Peak P), Distention contraction latency (DCL). Swallow risk index (SRI) derived from combination of four metrics (IBP, BPT, Peak P, and DCL). The data was analyzed on the online platform Swallow Gateway (swallowgateway.com; version 2019).

Results: Case 1: A 21-year-old female subject (normal control) denied of any gastrointestinal disorders (BEDQ score 0). Her metrics showed SRI 7.03 ± 1.48 (>15 indicate higher aspiration risk), IBP 22.10 ± 6.08 mmHg (normal: -1 ~ 28), BPT 0.68 ± 0.04 sec (normal: 0.54 ~ 0.92), Peak P 135.50 ± 0.06 mmHg (normal: 83 ~ 292) and DCL 0.56 ± 0.02 sec (normal: 0.39 ~ 0.65). All metrics were within normal range. Case 2: A 81-year-old man had a history of achalasia and recurrent laryngeal nerve palsy.

The BEDQ score was 30. His metrics revealed SRI 11.42, Peak P 79.83 mmHg. Low Peak P is compatible with weak hypopharyngeal contractility. Case 3: A 49-year-old

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P.123 man with amyotrophic lateral sclerosis came for stem cell therapy trial and evaluation for gastrostomy. The BEDQ score was 1. His metrics showed SRI (5.16 ± 1.6), IBP (12.9 ± 3.32 mmHg), BPT (0.62 ± 0.15 sec), Peak P (112.62 ± 3.01 mmHg) and DCL (0.35 ± 0.06 sec). All metrics were within normal range.

Conclusions: To our knowledge, this is the first report of pharyngeal HRIM studies using Swallow Gateway analysis in Taiwan. There were no adverse events in our patients.

Further studies with novel pharyngeal HRIM are warranted to confirm its utility in patients with suspected pharyngeal dysmotility as well as pharyngeal dysphagia.

抬腿誘發測試在高解析度食道壓力阻抗檢 查下對食道無效性蠕動患者之收縮期阻抗 值之影響 EFFECTS OF LEG ELEVATION MANEUVER ON CONTRACTILE SEGMENT IMPEDANCE IN PATIENTS WITH INEFFECTIVE ESOPHAGEAL MOTILITY: STUDIES WITH HIGH RESOLUTION IMPEDANCE MANOMETRY 翁銘彣 雷尉毅 洪睿勝 劉作財 易志勳 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: Contractile segment impedance (CSI) as a surrogate marker of mucosa integrity measured during high-resolution impedance manometry (HRIM) can predict gastroesophageal reflux disease (GERD) (Gastroenterology 2019). CSI measurement can be problematic in patients with ineffective esophageal motility (IEM) and significant hypomotility due to inadequate mucosa contact during esophageal smooth muscle contraction. Swallowing against the resistance of increased intra-abdominal pressure from leg elevation augments esophageal peristaltic vigor in IEM patients (Gastroenterology 2019).

Aims: We aimed to investigate the hypothesis whether there is consistency in CSI between standard wet swallows and swallows under leg elevation in reflux patients with normal motility and IEM. Methods: We performed HRIM in 27 GERD patients (age 45.1 ± 10.1 years, 14 female) with standard wet swallows (10×5 mL) and wet swallows under leg elevation (5x5 mL). CSI was assessed at 5 cm above the upper border of lower esophageal sphincter (swallowgateway.com). The impedance would be considered for CSI only if the lumen occluding peristaltic contraction > 30 mmHg. Between leg elevation (swallows under leg elevation) and baseline (standard wet swallows), distal contractile integral (DCI) was compared by paired t test and CSI was assessed for consistency through intra-class correlation coefficient (ICC).

Results: Of all 27 patients were classified according to Chicago Classification version 3.0, normal esophageal motility was found in 17 of them, while IEM was diagnosed in 10 of them. Leg elevation significantly increased DCI in both GERD patients with normal esophageal motility and IEM (normal: 2492.2 ± 259.0 vs.

1731.8 ± 168.4 mmHg.s.cm, p < 0.001; IEM: 1022.2 ±

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P.124 143.0 vs. 554.0 ± 59.2 mmHg.s.cm, p = 0.011). CSI was with excellent consistency between wet swallows with and without leg elevation in patients with normal esophageal motility and IEM (normal: 1112.5 ± 88.3 vs. 1121.5 ± 92.3 Ω, ICC = 0.891, p < 0.001, IEM: 2338.9 ± 408.0 vs.

2087.9 ± 354.3 Ω, ICC = 0.954, p < 0.001). In addition, leg elevation marginally increased the detection rate of CSI in IEM patients (92% vs. 82%, p = 0.06).

Conclusions: We have demonstrated that there is excellent consistence in CSI measurements between standard wet swallowing and wet swallowing during leg elevation in patients with normal esophageal motility and IEM. Our study suggests that HRIM with leg elevation maneuver can be a valuable adjunct in the measurement of CSI in patients with GERD, especially for those with significant esophageal hypomotility.

探討 Prucalopride 對 Sildenafil 引發之抑制 食道收縮生理之影響 EFFECTS OF PRUCALOPRIDE ON SILDENAFIL-INDUCED INHIBITION OF ESOPHAGEAL PERISTALTIC PHYSIOLOGY IN HUMANS 洪睿勝 翁銘彣 雷尉毅 易志勳 劉作財 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: Prucalopride, a high-affinity 5 hydroxytrypatamine 4 (5-HT4) receptor agonist, enhances esophageal peristalsis, but type 5 phosphodiesterase (PD5) inhibitor sildenafil inhibits secondary peristalsis in human esophagus.

Aims: This study aimed to test the hypothesis whether prucalopride could affect esophageal primary and secondary peristalsis subsequent to sildenafil application in healthy adults.

Methods: Fifteen healthy adults (men 13, mean age 30, 2242 years.) underwent high resolution manometry using a catheter containing 22 pressure transducers with one injection port located in mid-esophagus. Secondary peristalsis was performed by rapid air injections of 10 mL and 20 mL after ten water swallows for primary peristalsis. Two different sessions including acute administration of sildenafil 50 mg following pre-treatment with placebo or prucalopride 4 mg were randomly performed to test the effects on primary and secondary peristalsis. Frequency of primary and secondary peristalsis as well as relevant distal contractile integral (DCI) were investigated and compared.

Results: Prucalopride significantly increased the frequency of primary peristalsis subsequent to the administration of sildenafil (p = 0.03). Prucalopride significantly increased DCI of primary peristalsis subsequent to the administration of sildenafil (p = 0.03). There was no difference between prucalopride and the placebo in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (p = 0.11) or 20 mL (p = 0.29). Prucalopride had no effect on DCI of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (p = 0.09) or 20 mL (p = 0.58).

Conclusions: The 5-HT4 agonist prucalopride appears to influence esophageal motility by reversing sildenafil-induced inhibition of primary peristalsis, but failed to affect secondary peristalsis in health adults. The 5-HT4 agonist prucalopride has limited role in reversing inhibitory effects of PD5 mediating secondary peristalsis in human esophagus. Our study has demonstrated different physiological mechanisms underlying PD5-mediated modulation between primary and secondary peristalsis in human esophagus..

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胃食道逆流患者之食道酸鹼阻抗檢查特徵 單一中心之經驗 CLINICAL CHARACTERISTICS OF PATIENTS WITH GERD BASED ON AMBULATORY 24-HR IMPEDANCEPH MONITORING: A SINGLE CENTER EXPERIENCE

運用電阻抗測量食團內壓力探討因抬腿誘 發胃食道交界阻力增加之生理變化 UTILITY OF IMPEDANCEGUIDED MEASUREMENT OF THE INTRABOLUS PRESSURE DOMAIN TO CHARACTERIZE ESOPHAGO-GASTRIC OUTFLOW RESISTANCE INDUCED BY LEG LIFT

劉作財 易志勳 雷尉毅 洪睿勝 翁銘彣 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: 24-hr pH-impedance monitoring is the gold standard for gastroesophageal reflux disease (GERD) diagnosis.

Aims: This study aimed to compare reflux, clinical, and psychological characteristics among different phenotypes of GERD in a single center.

Methods: This study prospectively enrolled 83 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of heartburn and/ or regurgitation. Included patients further underwent ambulatory reflux testing for acid burden and symptom reflux association evaluation. All participants were categorized according to endoscopy and esophageal 24hr pH-impedance monitoring into four study groups: erosive esophagitis (EE), non-erosive reflux disease (NERD), and reflux hypersensitivity (RH), functional heartburn (FH).

We collected demographic data and subjects completed GERD questionnaire (GerdQ) reflux symptoms index (RSI), Taiwanese depression questionnaire (TDQ), and state–trait anxiety inventory (STAI) questionnaires.

Results: Among 83 patients, the number of diagnosis were 22 (26.5%) for EE, 4 (4.8%) for NERD, 34 (40.1%) for RH, and 23 (27.7%) for FH. Patients with EE had more acid reflux events than both RH and FH. In addition, patients with both EE and NERD had higher percentage of acid exposure time than both RH and FH. There was no difference in age, gender, body mass index (BMI), GerdQ, RSI, TDQ, STAI, total reflux, weak acid reflux, non-acid reflux, or percentage of abnormal esophageal motility among study groups.

Conclusions: We have demonstrated that patients with heartburn and/or regurgitation who visited our center for 24-hr impedance-pH monitoring were less likely to be diagnosed with NERD. Although acid reflux parameters may differ among different phenotypes of GERD, all patients had similar clinical and psychological characteristics, symptom severity, and esophageal motility.

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林霖 雷尉毅 翁銘彣 洪睿勝 易志勳 劉作財 梁書瑋 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: Pressure generated within the intrabolus domain are relevant to normal esophageal bolus transport and may detect abnormal esophageal outflow resistance.

Aims: This study measured the effect of leg-lift, a protocol designed to artificially increase esophageal outflow resistance.

Methods: Patients (GERD, globus and/or dysphagia history) referred for HRIM (MMS, 2.67 mm solid-state catheter) and diagnosed with ‘Normal’ motility were included. Supine liquid swallows were tested. Leg-lift was employed to generate esophageal outflow resistance by increasing abdominal pressure. Studies were analysed via Swallow Gateway web application (www.swallowgateway. com). Standard pressure topography metrics and three measures of the intrabolus pressure domain were calculated.

These were; i) mid-domain intrabolus distension pressure (DP, mmHg), ii) intrabolus ramp pressure (RP, mmHg/s), quantifying pressure change as the bolus is compressed between the peristaltic wave front and the EGJ and iii) time from mid-bolus distension to contraction (DCL, s). The bolus measures were combined to derive a pressure-flow index composite score of esophageal outflow resistance (PFI = [DP x RP] / DCL). Data are mean (SD).

Results: Thirty-four patients were included (aged 2573 years, 52% female). Leg lift increased EGJ integrated relaxation pressure from 20(8) to 31(21) mmHg (p = 0.004) and distal contractile integral increased from 1558(751) to 2413(1027) mmHg.cm.s (p < 0.0001) consistent with augmented of peristaltic vigor as a physiological response to resistance. All three bolus domain metrics were altered by leg lift. Intrabolus DP increased from 22(5) to 36(12) mmHg (p < 0.0001), intrabolus RP increased from 5(6) to 8(6) mmHg/s (p < 0.05) and DCL shortened from 2.5(1.0) to 2.1(1.0) s (p < 0.05). The PFI score increased from 74(145) to 232(248) (p < 0.001).

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P.127 Conclusions: Leg-lift is a simple provocative test that may help to reveal underlying esophageal dysfunction.

Impedance-guided measurement of the intrabolus pressure domain can quantify changes in esophageal outflow resistance and may have relevance to the diagnosis of EGJ outflow obstruction.

細胞激素在嚴重腐蝕性病患的變化 THE CHANGE OF CYTOKINE LEVEL AFTER SEVERE CORROSIVE INJURY 1,2

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鄭浩材 黃欣智 李青松 劉乃仁 顏宗海 1 林口長庚紀念醫院胃腸肝膽科系暨長庚大學醫學院 2 長庚大學醫學院臨床醫學研究所 3 林口長庚紀念醫院腎臟科系 Background: The ingestion of caustic substances induces an extensive spectrum of injuries to the aerodigestive tract which include extensive necrosis and perforation of the esophagus and stomach. But there is no study about cytokine change in corrosive patient.

Aims: The objective of this study is to survey the level change of cytokine after caustic agent ingestion.

Methods: his was a prospective study from 22 patients admitted to the Chang Gung Memorial Hospital in Tao-Yuan, Taiwan between Mar 2018 and Oct 2018 for treatment of caustic ingestion. These patients underwent EGD with blood serum collection within 24 hours of admission and mucosal damage was graded using Zagar’s modified endoscopic classification scheme. These patients were separated to two groups according the severity of Zagar’s classification: mild group (<2b) and severe group (≥2b). All patients’ cytokine was analyzed in same day and were followed in the outpatient clinic for a minimum of 6 months. Charts were record for the following data: the caustic substance, mortality, morbidity, and clinical outcome.

Results: Total 22 patients suffered from caustic substance swallowing agreed to join the study. There were 12 male and 10 female patients with a mean age of 52.3 ± 18.1yr (range, 18-80yr) in severe group and 48.6 ± 24.3yr (range, 25-93yr) in mild group. The rate of psychiatric disorder is 90.9% (10/11) in severe group and 36.4% (4/11) in mild group (P: 0.024). The amount of WBC is 15.4 ± 5.0X1000 in severe group and 11.5 ± 3.4X1000 (31/43) in mild group(P:0.078).

But, the lymphocyte of WBC 11.0 ± 9.1% in severe group and 23.0 ± 12.9% in mild group(P:0.013). The segment rate of WBC 84.2 ± 10.0% in severe group and 69.8 ± 16.6% in mild group(P:0.032). There is no different between severe and mild group in systemic complication. The complicated rate of gastrointestinal part is 45.5% (5/11) and 2 patients expired during following six months only in severe group (P=0.035). There is significant level cytokine change between severe group and mild group in Hu IL2, Hu IL17A, Hu MIP-1α and Hu TNF-α (P:0.05).

Conclusions: There are some cytokines is different between mild group and severe group of corrosive patients.

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P.128 內視鏡超音波對 T1/ T2 食道腫瘤分期的準 確性 --- 單一醫學中心的經驗 STAGING ACCURACY OF T1/ T2 ESOPHAGEAL TUMORS BY ENDOSCOPIC ULTRASOUND --- A SINGLE CENTER EXPERIENCE 1

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楊其穎 丁俊夫 黃文信 馮俊龍 陳政國 蕭望德 1 中國醫藥大學附設醫院消化系 2 中國醫藥大學附設新竹分院肝膽腸胃科 3 亞洲大學附設醫院肝膽腸胃科

Background: The staging esophageal cancer is the guide of treatment options and prognosis. The tools include endoscopic ultrasound, computer tomography (CT) and positron emission tomography (PET). The endoscopic ultrasound is important to evaluate the deep of tumor invasion, especial in early cancer status. For early esophageal cancer (T1 lesions), endoscopic resection can cure and provide organ protection, especially with the high morbidity associated with esophagectomy. T1b tumors (invading into the submucosa) can be subdivided into SM1, SM2, and SM3 tumor. It is difficult to evaluate the depth of submucosa layer invasions by endoscopic ultrasound.

Therefore, it is important to distinguish between T1b lesions or T2 lesions.

Aims: Evaluate the accuracy of T1/T2 staging by endoscopic ultrasound Methods: A retrospective analysis was performed from January 2014 to December 2018 and the pathology of endoscopic pathology revealed high grade dysplasia or carcinoma. The pre-treatment staging included endoscopic ultrasound, CT and/or PET. The Olympus Miniature probe UM2R (scanning frequency of 12 MHz) was used for predict the depth of invasion. The CT and/or PET were used for correct with lymph node (N staging) and distant metastasis (M staging). Analyzed patients with clinical T1/2 disease, as predicted by preoperative endoscopic ultrasound. It correlated with the pathologic stages after ESD or esophagectomy.

Results: One hundred sixteen patients (109 men and 7 women) with total 120 clinical T1/T2 lesions were indicated. The median age was 57 years (range, 38-88 years). Ninety patients were diagnosed as T1 lesions (cT1a: 51, cT1b: 39) and 26 patients were T2 lesions. Seventyseven patients received endoscopic submucosal dissection (ESD) and 39 patients received esophagectomy. The post ESD or surgical pathology diagnoses were squamous cell

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carcinoma (96%, 116/120), adenocarcinoma (2%, 2/120), adenosquamous carcinoma (1%, 1/120) and sarcomatoid carcinoma (1%, 1/120). The pathologic Tis and T1a tumors were 59 lesions; pT1b tumors were 53 lesions; pT2 tumors were 7 lesions and pT3 tumor was one lesion. The R0 resection rate of ESD and esophagectomy were 90% (ESD, 69/77) and 97% (38/39). The post. ESD R0 resection rate of pTis and pT1a lesion was 98% (48/49) and the post ESD R1 resection rate of pT1b lesion was 79% (22/28).

None clinical T1b lesion was diagnosed as pathologic T2 or T3 tumors after ESD or esophagectomy. Up to 69% of clinical T2 lesions (18/26) were diagnosed as pathologic T1b tumors, while 23% of clinical T2 lesions (6/26) were at the same stage. In cT2 lesions, the histology of pT1b tumors were squamous cell carcinoma with moderately differentiated (G2, 73%, 13/18), with poor differentiated (G3, 17%, 3/18), with well differentiated (G1, 5%, 1/18) and adenosquamous carcinoma (5%, 1/18); the history of pT2 tumors were squamous cell carcinoma with moderately differentiated (G2, 67%, 4/6) and with poor differentiated (G3, 33%, 2/6).

Conclusions: EUS has good diagnostic accuracy for staging early esophageal cancer and ESD have high R0 resection rate in T1a tumors. In our study, the clinical T1b lesions are pathologic T1a or T1b tumors. There is no pathologic T2 tumor in clinical T1b group. However, more than half of clinical T2 lesions are pathologic T1b tumors.

Although histology shows an increased proportion of G3 cancers in pathological T2 tumors, the number of cases is low and clinical application is low. In this study, it is retrospective, a single hospital clinical experience and need more data to further evaluate.

2020 消化系聯合學術演講年會

P.129 胃食道逆流病人使用三種不同氫離子幫浦 阻斷劑首月臨床症狀反應之比較：一南台灣 地區醫院之研究 THE INITIAL ONE MONTH CLINICAL RESPONSE OF PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE TREATED

BY LANSOPRAZOLE 30MG, RABEPRAZOLE 20MG, OR DEXLANSOPRAZOLE 60MG: A SOUTH TAIWAN DISTRICT HOSPITAL STUDY. 1,2

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medication. However, Rabeprazole did not occur with other side effects. Of these patients, 79 patients confirmed H. pylori infection but there wasn’t effect outcome.

Conclusions: Dexlansoprazole 60mg is the most effective drug and may be related to its dose. But it also has the highest chance of side effects. Different proton pump inhibitor drug should be selected based on the patient’s condition.

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葉欣榮 張君照 蘇宜輝 1 屏東枋寮醫院 2 臺北醫學大學附設醫院消化內科 Background: Gastroesophageal reflux disease (GERD) is a disease usually producing symptoms of heartburn and acid regurgitation. Others symptoms include chest pain and extraesophageal manifestations. We wanted to compare the effects of three proton pump inhibitors on patients after one month of treatment.

Aims: The study want to compare the one month clinical effects of three drugs in GERD patients.

Methods: Total of 165 Fangliao general hospital patients was diagnosed as having gastroesophageal reflux disease (GERD) by endoscopic study were enrolled in this study.

The patients were divided into three groups. The effects of the three drugs were compared by consulting the patient one month after using the drugs. 22 patients received Dexlansoprazole 60mg once-daily dose. 82 patients received Lansoprazole 30mg one time per day. 30 patients received Rabeprazole 20mg once a day. If the patient feels that the effect is not good, we will change the medicine or add medicine.

Results: Among all 165 patients, 117 were diagnosed as grade A, 42 were grade B, and 6 were grade C. After one month of treatment, we compared the treatment results by asking the patient’s satisfaction. Of the 22 users of Dexlansoprazole, 2 patients had side effect including headach, and others were satisfied with the efficacy of Dexlansoprazole. The probability of satisfaction is 90.9%.

Of the 82 patients using Lansoprazole, 72 were satisfied, with a satisfaction rate of 87.8%. One patient had headache side effect. But 10 patients changed medications. Of the 30 patients using Rabeprazole, 21 were satisfied with the effect of esophageal reflux treatment. The satisfaction rate is 70%. Nine patients were dissatisfied and changed their

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P.130 應用內視鏡超音波導引細針抽吸於腸胃道 術後之惡性淋巴結：東南台灣一區域教學醫 院的經驗 EUS GUIDED FINE NEEDLE ASPIRATION FOR MALIGNANT LYMPHADENOPATHY IN CASES AFTER GI SURGERY: EXPERIENCES IN A LOCAL HOSPITAL IN SOUTHEASTERN TAIWAN 吳佳憲 陳煥霖 白明忠 臺東馬偕醫院肝膽胃腸內科 Background: After resection of GI malignancy, it is challenging to determine the nature of a lymphadenopathy (LAP). It may indicate recurrence of previous malignancy or reactive inflammation. Tissue sampling and pathological diagnosis are important for determining following treatments. Few studies evaluate the role of EUS-FNA in patients with lymphadenopathy after the GI surgery Aims: Evaluate efficacy, safety, and clinical outcomes of EUS-FNA for LAP after GI surgery for malignancy in our hospital.

Methods: I retrospectively evaluated efficacy, safety, and clinical outcomes of EUS-FNA for LAP after GI surgery for malignancy in our hospital.

Three patients (mean age 72 y/o, range 71~75) with previous GI malignancy underwent EUS-FNA between March 2016 and September 2019.

First case had stage I gastric cancer that was curatively resected three years prior to the occurrence of intraabdomen LAP. Second case had stage IIB ampulla vater cancer who received Whipple operation one year earlier to development of LAP. Third case had intra-hepatic cholangiocarcinoma and developed mediastinum LAP one year after surgery.

We retrospectively evaluated technical success, clinical success, adverse event of procedure, and follow-up results Results: Overall technical success rate was 100% (3/3). All the pathological diagnosis of the LAPs were compatible with previous GI malignancy. There was no immediate procedure related bleeding, or GI tract perforation.

In the first gastric cancer case (71,M), enlarged intraabdominal LAP,14mm, was noted at the hepatogastric ligament and EUS-FNA confirmed metastatic adenocarcinoma. He then underwent chemotherapy and following up CT 6 months later showed resolution of the LAP. He died of sudden cardiac arrest 6 months later.

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In the ampulla vater case (75, F), one LAP 9.8mm was noted at para-aortic area and EUS-FNA confirmed metastatic carcinoma. He underwent chemotherapy and died of tumor progression 13 months later.

In the cholangiocarcinoma case(71, F),one 25mm mediastinum LAP was noted at subcarinal level, EUS-FNA conformed metastatic cholangiocarcinoma. Patient the underwent chemotherapy and liver metastasis occurred 3 months later.

In the study, median follow-up period was 12 months (range: 4-13 months).

Conclusions: EUS-FNA is a safe, and minimally invasive and useful procedure for LAP biopsy even in patients underwent GI surgery.

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P.132

生化製劑在發炎性腸炎失效之預測因子 PREDICTORS OF LOSS OF RESPONSE TO ANTI-TNFS THERAPY IN INFLAMMATORY BOWEL DISEASE

Cap 輔助內視鏡黏膜切除術可有效一次性完 整切除小於 10 毫米之直腸神經內分泌腫瘤 CAP-ASSISTED ENDOSCOPIC MUCOSAL RESECTION IS A PROMISING ONE-TIME PROCEDURE TO REMOVE RECTAL NEUROENDOCRINE TUMOR SMALLER THAN 10MM

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林煒晟 章振旺 陳銘仁 許自齊 王鴻源 1 臺北馬偕醫院胃腸肝膽科 2 臺北馬偕醫院大腸直腸外科

Background: Tumor necrosis factor-α (TNFα) antagonists have advanced the management of inflammatory bowel diseases (IBD) leading to an improvement of life quality with the reduction of surgeries and hospitalizations.

However, clinicians face many challenges when treating IBD with anti-TNF such as variable drug response, immunogenicity, and the loss of response.

Aims: The aim of this study is to evaluate the factors and management of loss of response of anti-TNF blockers in a real world practice.

Methods: A retrospective analysis was conducted on IBD patients who had received at least one course of anti-TNF therapy, retrieved from a single center in Taipei, Taiwan.

The definition of loss of response was those patients requiring dose intensification or those who had clinical symptom after a period of anti-TNF use Results: There were 41 patients receiving 64 times of antiTNF therapy. Fourteen patients (25.9%) had lost response of anti-TNF therapy. The mean time to lost response was 6.7 months (range 1-15). Two patients (14.2%) suffered from lost response during induction phase. There were no differences in age, gender, duration of biologics, duration of initial diagnosis to using biologics, and classification of IBD. As for the medication before and during biologic usage, there were no differences in 5-aminosalicylic acid, steroid and immunosuppressant agent in the response and response and lost response groups. The rate of steroid and immunosuppressant agent free were 51.4% and 29.4%. The lost response group had higher steroid free rate (75% vs 28.6%, p=0.005). There were no differences in immunosuppressant free, timing of quit combination therapy in both groups.

Conclusions: Managing loss of response to biologics is a frequent challenge for clinicians who manage patients with moderate to severe IBD. Deescalating steroid may precede loss clinical response to anti-TNF therapy.

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方華珍 卓庭毅 鄭勝偉 吳明順 1 萬芳醫院消化內科 2 臺北醫學大學醫學院醫學系

Background: There is a recent tendency that the detection of rectal neuroendocrine tumor (NET) is increasing in eastern Asian countries. Reasons for this phenomenon are attributed not only to the widely availability of colonoscopic surveillance but also to the increased awareness of endoscopists and pathologists concerning the significance and appearance of rectal NET .

Aims: Most rectal NET is relative small in size and low mitotic rate and variety endoscopic resection method are considerably feasible. Currently there is no common recommendation of optimal endoscopic treatment for such lesion. The aim of our study is to evaluate the optimal onetime endoscopic treatment modality for rectal NET smaller than 10mm.

Methods: We extracted the data of rectal NET smaller than 10mm which were being resected endoscopically from 2014 to 2019 in Wan Fang Hospital.

Results: During 2014-2019, 44 patients were pathologically diagnosed to have rectal NET, 37 (83%) patients had rectal NET size smaller than 1cm and being removed either simple polypectomy, endoscopic mucosal resection (EMR) or modified EMR. Another 7(17%) patients had rectal NET size larger than 10mm and removed by using ESD technique. Of 37 patients with rectal NET smaller than 10mm , 10 (27%) patient had received polypectomy, 18 (48.6%) had received EMR, and 9 (24%) had modified EMR. The successful resection rate with clear margin of polypectomy, EMR and modified EMR were 20%, 22.2% & 88.8% respectively. There was significant difference of successful removal between EMR and modified EMR (22% vs 88.8%, p=.04533) Of one patient who had margin involved after modified EMR had received lower anterior resection and pathological study revealed a multi-centricity NET, which was exceptionally rare. All patients whom underwent modified EMR had

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P.133 prior endoscopic ultrasound (EUS) checked and all tumors were confined to subepithelial or submucosal layer. Most patients in conventional EMR group had no prior EUS assessment and the tumor was being resected as soon as the lesion was detected.

Conclusions: Cap-assisted EMR technique is a safe and promising one-time procedure to remove rectal NET smaller than 10mm.

提昇消化道內視鏡初學者對「大腸黏膜表面 病灶」判讀能力之培訓計劃 – 初步成果分析 A TRAINING PROGRAM FOR IMPROVING COMPETENCE OF OPTICAL BIOPSY OF COLORECTAL SUPERFICIAL LESIONS FOR THE BEGINNERS OF GI ENDOSCOPY – PRELIMINARY RESULTS 1,2

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林裕民 孫灼基 張麗文 劉玉華 楊國卿 1 新光吳火獅紀念醫院胃腸肝膽科 2 天主教輔仁大學醫學系

Background: Application of image-enhanced endoscopy (IEE) is comparable to histological examination for the evaluation of superficial colorectal neoplasms. It remains a challenge for the beginners of endoscopy to assess the lesions with confidence.

Aims: We aim to improve the competence of optical biopsy with IEE through an organized training program.

Methods: We organized a “Quality Colonoscopy” training program for the beginners of GI-Endoscopy. We enrolled GI trainees and junior Attending Physicians (V1-V5) as attendees. We invited experienced endoscopists qualified as advisers by Gastroenterology Society and Digestive Endoscopy Society of Taiwan to be the trainers /raters of the program. The trainers provided mini-lectures at a frequency of once/2wks to introduce the key features of superficial colorectal lesions and key quality indicators of colonoscopy. The descriptions of superficial colorectal lesions were based on mutually agreeable international classifications including Paris, NICE, JNET, and WASP classifications. The raters applied image-based questions as objective measurements for the trainees after minilectures through a web-based interactive response platform (Kahoot). The performance was rated (Good: >75%; Average: 50%-75%; Failed: <50%) according to the accuracy rate of the responding to the questions.

Results: Eight junior physicians (as attendees) and two advisers (as trainers/raters) participated in this program. There were six mini-lectures paying attention to “IEE” and “quality issues of colonoscopy” provided between September 2019 and December 2019. A total of 94 questions covering multi-dimensions of “quality colonoscopy” were applied after mini-lectures. The overall accurate responding was 65.8%. The accurate “morphology assessments” of the superficial colorectal lesions based on Paris, NICE, JNET and WASP classifications were 73.9%,

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P.134 67.6%, 57.6% and 61.9% respectively. The accuracy of “quality assessments” was 64.0%. The accuracy of “appropriate managements of superficial colorectal lesions” was 57.0%.

Conclusions: The assessment of morphology of colorectal lesions by using Paris classification is approaching a good level, accordingly, it could be routinely applied in the standard colonoscopy report. The assessments of the features of colorectal lesions by using NICE; JNET and WASP are average; these classifications should be applied with caution.

In conclusion, there’s room of improvement for the beginners of GI-Endoscopy to assess superficial colorectal lesions. Continuous organized educational activities and measurements should be provided to improve physician’s competence and to maintain the quality of endoscopy.

內視鏡與手術治療對於 T1 大腸直腸癌長期 存活之比較：系統回顧與統合分析 LONG-TERM OUTCOMES OF ENDOSCOPIC RESECTION VERSUS SURGERY FOR T1 COLORECTAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS 1,2

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葉人豪 曾政豪 林志文 李青泰 蕭博仁 吳宗勤 1 王文 1 義大醫院胃腸肝膽科 2 義大大昌醫院胃腸肝膽科 3 義大癌治療醫院胃腸肝膽科

Background: Optimal treatment for T1 colorectal cancer has been controversial.

Aims: This study aimed to investigate the long-term outcomes after endoscopic resection (ER) and its comparison to primary or additional surgery.

Methods: A systematic review was performed via meticulous search from PubMed, Embase and Cochrane databases. Primary outcomes were overall survival, disease specific survival and recurrence free survival at 5-years.

Secondary outcomes included local recurrence and distal metastasis. For meta-analysis of time-to-event data, hazard ratio (HR) was used and expressed with 95% confidence interval (CI).

Results: A total of 15 full-published studies with 19265 patients (6560 ER, 12705 surgery) were included. The pooled overall survival (HR 1.18, 95% CI = 1.04 – 1.34) and recurrence free survival (HR 1.51, 95% CI 1.20 – 1.91, Figure 1a) was better for surgery. On the other hand, there was no difference in disease specific survival (HR 0.91, 95% CI = 0.51 – 1.63). Subgroup analysis suggested patients with primary ER and additional surgery had similar recurrence free survival compared to primary surgery (HR 1.31, 95% CI 0.88 – 1.96, Figure 1b). In addition, high risk histology features included poor differentiation or mucinous histology, tumor budding, and rectal cancers were associated for recurrence; and poor differentiation and lympho-vascular invasion were significant risk factors for lymph node metastasis. ER also had less procedure related adverse events (2.1% vs. 10.4%, p < 0.001) Conclusions: Compared to primary surgery, ER is safe and effective for T1 colorectal cancer. However, additional surgery should be recommended for high risk histologic features.

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P.135 低 體 積 Polyethylene Glycol 單 一 劑 量 給 藥 加 上 bisacodyl 與 標 準 劑 量 Polyethylene Glycol 分次給藥於上午施行的大腸鏡臨床效 用比較 COMPARING SINGLE-DOSE LOWVOLUME PEG PLUS BISACODYL VS. SPLIT-DOSE PEG FOR BOWEL PREPARATION IN MORNING COLONOSCOPY 1

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黃唯誠 張智翔 鄭勝偉 卓庭毅 黃士斌 陳俊男 1 1, 2 1, 2 1, 2 1, 2 鄭照霖 陳永發 粟發滿 吳明順 連吉時 1 臺北市立萬芳醫院- 委託財團法人臺北醫學大學辦理 2 臺北醫學大學 Background: Colorectal cancer incidence rate has increased in recent years, and colorectal cancer has come to the top of cancer incidence ranking of Taiwan.

Colonoscopy is the best method to detect colorectal cancer and colonic polyps. Studies showed that adenoma detection rate positive correlation with good bowel preparation. That makes bowel preparation an important issue. Polyethylene Glycol (PEG) is widely used for bowel preparation for its efficacy and safety. But, there are many different adjunctive, dose, the timing of administration in PEG preparation. Some may decrease patient tolerability due to large fluid volume, and some may influence the patient’s life and sleep quality when performing bowel preparation.

Aims: Here, we conduct a clinical trial about adding another laxative agent to morning single dose low-volume PEG. To see if this new regimen could have non-inferior efficacy and lower life/sleep impact compared with the standard regimen.

Methods: This is a single-center, prospective, randomized, investigator-blind study in an academic tertiary- care center.

One hundred and twenty-two patients randomly allocated to receive Bisacodyl (15mg, the night before procedure) and single dose of low-volume PEG (2 liters, morning of procedure; group A, n=61), or traditional standard volume PEG (two liters of PEG at the night before procedure followed by two liters in the morning of procedure; group B, n=61). The primary endpoint of this study is to compare the satisfactory bowel preparation proportion in both groups, defined by OBPS (Ottawa bowel preparation scale) ≤ 6.

The side effects, daily life activity interference (tolerability), compliance of the bowel preparation regimen were also compared in both groups.

Results: Overall, there were 122 patients randomly

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allocated to receive low-volume PEG plus bisacodyl (group A, n=61) or traditional standard volume PEG (group B, n=61). Eleven patients were not showing up as scheduled.

In the end, there were 111 patients included in the analysis of primary endpoint (53 patients in group A and 58 patients in group B). The demographic characteristics at baseline were no difference in both groups [Group A: male 63.9%; Age 48.38 ± 12.59; Body mass index (BMI) 25.03 ± 4.78.

Group B: male 67.2%; Age 50.25 ± 11.02; BMI 25.08 ± 4.44]. The proportion of decreased defecation less than three times per week were also similar in both groups (9.4% in group A and 5.2% in group B, P=0.476) The satisfactory bowel preparation rate was 47.1% (mean OBPS: 5.60) in group A and 52.9% in group B (mean OBPS: 4.98). The equivalence test (TOST; two one-sided test) was non-significant [90% CI (confidence interval): -0.21 - 0.09; Z = 0.996; p = 0.160, given equivalence bounds of -0.150 and 0.150 and an alpha of 0.05.]. The NHST (Null hypothesis significance test) was nonsignificant (95%CI: -0.24 - 0.12; Z = -0.664; p = 0.507, given an alpha of 0.05). Based on the equivalence test and the null-hypothesis test combined, we can conclude that low-volume PEG plus bisacodyl was no difference to traditional standard volume PEG, but was not noninferiority to traditional standard volume PEG. In each bowel segment, there was no significant difference in mean segment OBPS except for left side colon and fluid amount (Right side colon: 1.90 in group A and 1.86 in group B, P=0.57; Transverse colon: 1.28 in group A and 1.16 in group B, P=0.42; Left side colon: 1.43 in group A and 1.20 in group B, P=0.04; Fluid amount: 1.00 in group A and 0.72 in group B, P=0.02).

The interference scores in the sleep, work, and daily activity were not differenced in both groups (Sleep: 1.49 in group A and 0.90 in group B, P= 0.09; Work: 0.72 in group A and 0.59 in group B, P= 0.82; Daily activity: 0.64 in group A and 0.76 in group B, P=0.19). The side effects in both groups were also not different (Nausea: 42.6% in group A and 27.9% in group B, P=0.053; Vomiting: 16.4% in group A and 18.0% in group B, P=1; Bloating: 11.5% in group A and 23.0% in group B, P=0.22; Abdominal pain: 13.1% in group A and 9.8% in group B, P=0.64; Headache: 1.6% in group A and 4.9% in group B, P=0.62; Dizziness: 6.6% in group A and 4.9% in group B, P=0.71). The scaled feature importance analysis showed that the most important in choosing the preparation regimen is effectiveness. The two groups have no difference in regimen compliance and diet control (Compliance in diet control: 98.1% in group A and

2020 消化系聯合學術演講年會

P.136 100% in group B, P=0.477; Compliance in regimen: 90.6% in group A and 89.7% in group B, P=1.000). The ranking of importance during bowel preparation for all patients was preparation effectiveness, less sleep interference, less work interference and less daily life interference.

Conclusions: The effectiveness of Bisacodyl plus single-dose low-volume PEG was not different from the conventional 4-liter split-dose PEG, but we could not prove the non-inferiority. The compliance, tolerability and side effects of both groups were identical.

血清麩胺轉酸酶 (γ-GT) 與大腸直腸腺瘤發 生率之關係 RELATIONSHIP BETWEEN SERUM GAMMA-GLUTAMYL TRANSFERASE LEVEL AND COLORECTAL ADENOMA 1

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洪子瞻 楊宏志 陳祈玲 高嘉宏 劉俊人 陳銘仁 3 3,4 3,4 3,4 王鴻源 郭仰哲 余羅業 胡光濬 1 國立臺灣大學醫學院附設醫院內科部 2 國立臺灣大學醫學院臨床研究所 3 馬偕紀念醫院內科部胃腸肝膽科 4 馬偕紀念醫院臺北健康檢查中心

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Background: Cost-effective serology tests may increase the predictive accuracy of colonoscopy for colorectal c a n c e r s c r e e n i n g . R e p o r t e d l y, g a m m a - g l u t a m y l transferase (GGT) is associated with oxidative stress and carcinogenesis and has been found to be elevated in the serum of cancer patients and colorectal adenoma tissue.

Aims: We aimed to investigate the association between serum GGT levels and colorectal adenoma.

Methods: This single-center, health examinationbased cohort enrolled 4669 subjects from 2006 to 2015.

Baseline characteristics, laboratory data, bidirectional g a s t r o i n t e s t i n a l e n d o s c o p y, a n d t r a n s a b d o m i n a l ultrasonography were used to evaluate the severity of fatty liver.

Results: We found an elevated median GGT level in subjects with tubular adenoma compared with those without (23 IU/L and 20 IU/L, p<0.001). A GGT cutoff of ≥20 IU/L reached a maximal Youden index in receiver operating curve (ROC) analyses. Subsequent regression analyses showed an odds ratio of 1.46 (95% CI 1.17–1.82, p<0.001) for age, body mass index, diabetes diagnosis, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and positive Helicobacter pylori urease test, all being associated with an increased incidence of colon adenoma. Subgroup analysis showed that the odds ratio (OR 1.27, 95% CI 1.15–1.68, p<0.001) is only significant and highest in patients with a negative or mild fatty liver and an ALT level of ≤40 IU/L. Conclusions: The results suggested a positive correlation of GGT with colon adenoma incidence and a predictive value with a cutoff point of >20 IU/L, which is within the normal range. The effect may be most prominent for those without steatohepatitis.

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克隆氏症併發腹腔內膿腫的處理：一醫學中 心經驗 MANAGEMENT OF INTRAABDOMINAL ABSCESSES IN CROHN’S DISEASE: A SINGLE CENTER EXPERIENCE

大腸鏡檢查前使用 LINE 再教育確認理想清 腸：一項前瞻性，大腸鏡檢查醫師蒙蔽，隨 機，對照試驗 LINE RE-EDUCATION BEFORE COLONOSCOPY TO CONFIRM OPTIMAL BOWEL CLEANSING: A PROSPECTIVE, COLONOSCOPISTBLINDED, RANDOMIZED, CONTROLLED TRIAL

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林煒晟 章振旺 陳銘仁 許自齊 王鴻源 1 臺北馬偕醫院胃腸肝膽科 2 臺北馬偕醫院大腸直腸科

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Background: Approximately 10% to 30% of patients with Crohn’s disease (CD) will spontaneously develop an abdominal abscess during the disease course. The timing of surgery and medical therapy is controversial.

Aims: The aim of this study is to evaluate the outcomes from different treatment approaches to intra-abdominal abscess in CD. Methods: We performed a single-center, retrospective, observational cohort study in patients with CD complicated by intra-abdominal abscess. We corrected the data of abscess size and location, treatment modality, and clinical outcome.

Results: From January 2010 to December 2019, there were 111 CD patients diagnosed in our hospital and eight patients (7.2%) had intraabdominal abscess during follow up. Median age at inclusion was 22 years (inter-quartile range:15–26), 5 (62.5%) patients were male. The most common location of CD were ileocolic type (50%), followed by ileum (25%) and colonic type (25%). Median disease duration before abscess occurrence was 11 (1–44.5) months. The median size of abscess was 40 (25–68) mm. With regard to the common location of abscess were ileocecal valve (37.5%) and ileum (25%). Four patients (50%) received surgical intervention directly. Among these four patients received CT-guided drainage, the drainage time were from 2.5 weeks to 3 months. Two patients (50%; 2/4) received surgery, one patient relieved himself and one patient expired after surgery.

One patient (25%, 1/4) received steroid and the other patient received biologic therapy during abscess drainage. There was no relapse of intra-abdominal abscess in 7 patients after 2-year follow-up.

Conclusions: In this study, abscess formation was noted in about 7.2% of patients with CD, with 50% of abscesses occurring in the ileocecal valve. The majority (87.5%) of CD patients complicated by intra-abdominal abscess require definitive surgical treatment. Management of CD related intra-abdominal abscesses is challenging and requires the expertise of multiple specialties working in concert.

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高偉育 張君照 張甄 林寶英 唐瑞祥 1 臺北醫學大學附設醫院內科部胃腸科 2 臺北醫學大學醫學院內科學科 3 臺北醫學大學臨床醫學研究所

1,2

Background: Several methods had previously been tried to improve patient compliance with instructions for bowel preparation.

Aims: This randomized prospective study aimed to investigate whether LINE re-education (LRE) before colonoscopy to confirm optimal bowel cleansing and the impact on quality indicators of colonoscopy performance, such as polyp detection rates.

Methods: A prospective colonoscopist-blinded study was conducted. All patients received regular instructions during a visit to discuss colonoscopy. Those scheduled for colonoscopy were randomly assigned to receive LRE on the day before colonoscopy (LRE group) for bowel preparation or no LRE (control group). The primary outcome was the rate of adequate bowel preparation defined as Boston bowel preparation scale ≥ 6 at the time of colonoscopy. The secondary outcomes included polyp detection rate (PDR), rate of non-compliance with instructions, patients level of discomfort, cecal intubation rate, cecal intubation time, and withdrawal time.

Results: A total of 254 patients were randomized, 127 to the LRE group and 127 to the control group. One patient canceled colonoscopy. In an intention-to-treat analysis of the primary outcome, adequate preparation was found in 92.8% vs 84.1% of LRE and control patients, respectively (P=0.032). PDR was 42.9% vs 42.5% in the LRE and control group, respectively (P=0.957). Among patients with successful colonoscopy, the Boston bowel preparation scale were 6.9±1.4 in the LRE group and 6.6±1.6 in the control group (P=0.059). No significant differences were observed between the two groups with regard to rate of non-compliance with instructions, patients level of discomfort, cecal intubation rate, cecal intubation time, and withdrawal time.

Conclusions: LRE about the details of bowel preparation on the day before colonoscopy improved the quality of bowel preparation.

2020 消化系聯合學術演講年會

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P.140

同性戀艾滋病患者大腸疾病之臨床及病理 特徵 CLINICOPATHOLOGICAL CHARACTERISTICS OF COLORECTAL DISEASES IN HOMOSEXUAL AIDS PATIENTS

不明原因腸系膜靜脈硬化性大腸炎的臨床 表現、診斷及治療 IDIOPATHIC MESENTERIC PHLEBOSCLEROTIC COLITIS IN TAIWAN : CLINICAL PRESENTATIONS, DIAGNOSIS, AND TREATMENT

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林寶英 劉欣怡 莊涵琄 唐瑞祥 張君照 1 臺北醫學大學附設醫院消化內科 2 臺北醫學大學消化內科 3 臺北醫學大學附設醫院感染科

Background: Men who have sex with men (MSM) have reemerged as the major risk population in Taiwan since 2008 .As of 2017, there were over 35,935 cases of HIV-1 infection in Taiwan, 62.31% were MSM. Inflammation of the rectum and colon, is a condition that is not uncommon among (MSM) patients.

Aims: To identify colorectal diseases in Homosexual AIDS patients.

Methods: We reviewed medical records of total 534 Homosexual AIDS patients in Taipei Medical University Hospital who performed colonoscopy for evaluation of different symptoms. Among them, twenty two cases were identified colorectal diseases. Parameters including general characteristics, site of the lesion, colonoscopic appearance histopathologic findings and treatment status were reviewed retrospectively.

Results: Our study included 22 patients, ranging in age from 26 to 58 years. Among them, 11 cases were diagnosed syphilitic colitis, 5 cases were cytomegalovirus colitis, 6 cases were amebic colitis and one case was shigella colitis respectively. One patient had concurrent amebic and syphilitic colitis. The symptoms most frequently requiring colonoscopy were diarrhea, bloody stool, mucus discharge, anal pain, tenesmus and change bowel habit. Most lesions were located in rectum (9 cases), right sided colon (13 cases) and left sided colon (5 cases). Colonoscopic findings were inflamed erythematous mucosa, ulcerative lesions and protruding lesion.

Conclusions: The clinical presentations of these colorectal diseases in homosexual AIDS patients can mimic other common conditions such as inflammatory bowel disease, rectal solitary ulcer or malignancy. Long-term prognosis of these diseases are excellent but it can be influenced by patient and physician delays. Thus, a high level of suspicion, particularly in HIV-positive homosexual patients, is crucial in order to avoid incorrect diagnosis, and delayed therapy.

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陳文昭 高健能 林寶英 張立群 許文峰 凃佳宏 3,4 1,2 邱瀚模 張君照 1 臺北醫學大學附設醫院內科部消化內科 2 臺北醫學大學內科部消化內科 3 國立臺灣大學醫學院附設醫院胃腸肝膽科 4 國立臺灣大學醫學院附設醫院健康管理中心

3,4

Background: Idiopathic mesenteric phlebosclerotic colitis was a rare disease entity of intestinal ischemia which was predominant in Asian populations. Idiopathic mesenteric phlebosclerotic colitis was caused by venous obstruction because colonic and mesenteric venous calcification.

Aims: We tried to investigate idiopathic mesenteric p h l e b o s c l e r o t i c c o l i t i s i n Ta i w a n f r o m c l i n i c a l presentations, diagnosis, and treatment.

Methods: We retrospectively reviewed who were diagnosed of idiopathic mesenteric phlebosclerotic colitis from NTUH and TMUH in the past 10 years.

Results: A total of 11 cases was presented in our case series. The average age of the patients was 59 (±6.77) years old and female was predominant with a percentage of 54.5%. More than half of our patients had a history of herbs consumption. Their symptoms varied from asymptomatic to lethal, such as mechanical ileus. The most common colonoscopic finding was the dark purple discoloration and decreased vascularity over the edematous mucosa. In our case series, 9 patients showed disease progression free after conservative treatment alone. In contrast, two cases required surgical intervention due to mechanical ileus.

Conclusions: Although the incidence of idiopathic mesenteric phlebosclerotic colitis was rare, some of the idiopathic mesenteric phlebosclerotic colitis may be lethal.

Thus, we would like to remind every colonoscopist of this rare disease through our study.

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P.141 STAT3 抑制大腸癌類癌幹細胞中小分子核 糖核酸 miR-30a-5P 的分子機轉研究 STAT3 DOWNREGULATES MIR-30A5P FOR TUMOR SURVIVAL IN CD133/ LGR5-POSITIVE COLORECTAL CANCER STEM-LIKE TUMORSPHERES 1,2

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程俊嘉 張君照 何愛生 楊必玲 林信吉 1 臺北醫學大學附設醫院消化內科 2 長庚大學放射醫學研究院輻射生物研究中心 3 臺北振興醫院胃腸肝膽科 Background: STAT3, a transcriptional factor involving in tumorigenesis and initiation of cancer stemness, is a potential therapeutic target against cancers. Recent studies reveal that STAT3 not only mediates gene transcription but also participates in microRNA suppression. However, the detailed mechanism regulating microRNAs (miRNAs) expression by STAT3 is obscure.

Aims: In this study, we intend to investigate the STAT3downstream miRNA using small RNAseq platform to uncover the potential miRNAs involving in formation of CD133/LGR5-positive colorectal cancer stem-like tumorspheres.

Methods: Small RNAseq was used to investigate the differential microRNAs in colorectal cancer cells-derived tumorspheres and STAT3 knockdowned strain. With RNAseq data comparing to the gene targets predicted by TargetScan (http://www.targetscan.org/vert_72/), we are able to uncover the miRNA-mediated gene consequently. qPCR and Western blots were used to validate the findings and understand the potential molecular mechanism.

Results: We found 10 miRNAs increased but 13 miRNAs decreased in the HT29-derived tumorspheres. Compared to the small RNAseq result from HT29shSTAT3, we figured out that 4 STAT3-mediated miRNAs in HT29-derived tumorspheres, including upregulation: hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p; and downregulation: miR-30a-5p. The hsa-miR-4521 was associated with worse overall survival probability but miR-30a-5p with better overall survival probability in patients with rectum cancer (http://kmplot.com/analysis/). Compared with the RNAseq findings from HCT116- and HT29-derived tumorspheres, we found and validated TSC22D2, CALB2, and HSPA5 were mediated by STAT3-miR-30a-5p axis that overexpressed in colorectal tumorspheres. In addition, transfection of miR-30a-5p significantly reduced cell viability and HSPA5 which involving in anti-apoptosis in

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HT29 cells.

Conclusions: In conclusion, we found that STAT3 mediated miRNA expression in the colorectal stemness tumorspheres, including miR-4521 and miR-30a-5p that associated with survival probability in clinical patients with rectum cancer. In addition, STAT3-miR-30a-5p increased TSC22D2, CALB2, and HSPA5 may be involved in cancer stemness, exacerbating anti-apoptosis in colorectal cancer.

2020 消化系聯合學術演講年會

P.142 盲腸到達時間延長與息肉發現率下降沒有 相關性 - 單中心回溯性研究 PROLONGED CECAL INSERTION TIME IS NOT ASSOCIATED WITH DECREASED POLYP DETECTION – A SINGLE-CENTER, RETROSPECTIVE STUDY 1

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analysis when controlling for patient age, sex and withdrawal time (OR=1.0000, 95% CI 0.9996-1.0004, p=0.9280).

Conclusions: Prolonged cecal insertion time was not associated with a decrease in PDR.

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甘育安 張君照 高偉育 唐瑞祥 簡錫淵 1 臺北醫學大學附設醫院消化內科 2 臺北醫學大學醫學院醫學系肝膽胃腸內科學科 Background: Adenoma detection rate (ADR) is an important colonoscopy quality parameter, which is positively associated with longer withdrawal time and correlated with the risk of interval colorectal cancer. Recent studies showed a high degree of correlation between ADR and polyp detection rate (PDR), which is much easier to be calculated. The effect of cecal insertion time on polyp detection is unclear.

Aims: To assess the association between cecal insertion time and PDR. Methods: This study included 50- to 75-year-old subjects undergoing an elective colonoscopy for screening or surveillance of colorectal neoplasms during Aug. 2014 to Jul. 2019 at Taipei Medical University Hospital. Patients were excluded from the retrospective analysis if patients had previously received colectomy, an inadequate or poor bowel preparation, undocumented insertion or withdrawal time, a failed cecal intubation. All colonoscopies included were performed under monitored anesthesia care and without fellow involvement. The primary outcome was cecal insertion time and its association with PDR. Results: Among 2148 included study subjects, the mean age was 61.4 years (standard deviation [SD] 6.84) and 1018 were male (47.4%). The median cecal insertion time was 290 seconds (interquartile range [IQR] 211; 410) and withdrawal time was 621 seconds (IQR 453; 901). We identified 1541 (71.7%) subjects with colorectal polyps.

On univariable analysis, longer cecal insertion time was significantly related to female sex (vs. male, p<0.0001) and older age (p<0.0001), but not related to bowel preparation quality (fair vs. excellent or good preparation, p=0.5875).

Cecal insertion time did not correlate with withdrawal time (p=0.2351). Despite patients with colorectal polyps had significantly shorter cecal insertion time and longer withdrawal time (p<0.0001), shorter cecal insertion time was not associated with finding a polyp on multivariable

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P.143 加護病房床邊大腸鏡：一個醫學中心經驗 BEDSIDE COLONOSCOPY IN THE INTENSIVE UNIT: EXPERIENCE IN A MEDICAL CENTER 吳東龍 顏旭亨 彰化基督教醫院胃腸肝膽科 Background: Colonoscopy is rarely performed in the intensive care unit (ICU) because of the high risk of the proceudure. Colonoscopy is generally performed in ICU for suspected ischemic colitis, decompression of colonic distension and lower gastrointestinal hemorrhage. The bowel preparation and the patient condition are different from routine colonoscopy practice. Patients in the ICU usually have more co-morbidities and have a mortality rate.

The result of urgent or emergency colonoscopy in ICU is rarely reported in the literature.

Aims: We would like to review the medical record and colonoscopy reports in ICU. Collecting lab data and reports then figure out the relationship between who received colonoscopy in ICU and mortality risk during the hospital course.

Methods: Changhua Christian Hospital is a medical center in middle Taiwan with 1222 beds including 130 ICU beds.

All 5341 colonoscopy was done during the period. Amount 370 times in-hospital colonoscopy was done between Jan 2019 and Oct 2019. We identified 48 colonoscopies performed in the ICU and 6 cases were excluded due to repeat procedures. The study was performed with retrospective with review of the medical records and colonoscopy reports.

Results: Total 42 cases bedside colonoscopy were done during 10 months in our ICU. The average patient age is 71.95-year- old. There are 23 male and 19 females. Twenty of the patients were survived to discharge. The indication for colonoscopy includes bloody stool passage ( n=31) , tarry stool (n=3) , suspect of clostridium difficile infection (n=1) , suspected colonic cancer (n=2) , bleeding after negative upper endoscopy (n=2) , heart transplant surveillance (n=2), and bowel obstruction(n=1).

The findings of colonoscopy includes colitis (n=14), rectal ulcers ( n=7), colon cancer (n=6), hemorrhoid bleeding ( n=4), bleeding of unknown origin ( n=2), angiodysplasia (n=2), volvulus (n=1) and non-diagnostic (n=5).

The mortality group ( n=22) had significant different higher BUN level (84.3 +/- 58.5 vs 41.5 +/- 28.0 , p=0.005)

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compared to alive group ( n=20). After selected variables with p-value<0.10 from crude model to enter multivariate adjustment model, higher platelet level may reduce risk of mortality but no statistically significant (P-value=0.151).

The higher albumin level may reduce risk of mortality but borderline statistically significant (P-value=0.063). The higher BUN level may predict the risk of mortality (P-value = 0.026).

Conclusions: Most of the bedside colonoscopy were done in ICU due to bloody stool passage. The major finding of colonoscopy were variable. Patients who received bedside colonoscopy in ICU had high BUN level may have higher mortality rate during the hospital course than others.

2020 消化系聯合學術演講年會

P.144

P.145

直腸神經內分泌腫瘤與內視鏡切除：區域醫 院的經驗 ENDOSCOPIC RESECTION FOR RECTAL NEUROENDOCRINE TUMOR: A REGIONAL HOSPITAL EXPERIENCE

擾亂細胞微管可激活 PERK 和阻止 G2/M 而導致大腸直腸癌細胞凋亡 ACTIVATION OF PERK CONTRIBUTES TO APOPTOSIS AND G2/M ARREST

BY MICROTUBULE DISRUPTORS IN HUMAN COLORECTAL CARCINOMA CELLS.

溫奕志 辛政憲 黃仁杰 李政祺 陳俊欽 陳季宏 陳鄭弘堯 陳仕豐 澄清綜合醫院中港院區胃腸肝膽科 Background: The incidence of rectal neuroendocrine tumors (NETs) is increasing because of the policy for colorectal cancer evaluation in Taiwan. Through the endoscopic screening, rectal NETs were found and endoscopic resection, include biopsy, endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD), were done.

However, there was no strong evidence of clinical outcomes in endoscopic resection for rectal NETs. This study would evaluate the rates of histologically complete resection and recurrence after endoscopic resection for rectal NETs. Aims: Evaluate rates of histologically complete resection and recurrence after endoscopic resection for rectal NETs Methods: Patients who were found rectal NETs and received endoscopic resection during January 2014 to October 2019 at Chen-Ching hospital were included in our retrospective study.

Primary outcomes were histologically complete resection and recurrence rates after endoscopic resection. Histologically complete resection was defined as the absence of tumor invasion in the margin of resected specimens Results: Among 16 patients, 10 patients (62.5%) were treated with conventional EMR, 5 (31.2%) received biopsy, and 1 (6.3%) was arranged ESD. The median tumor size was 5.5 mm (range, 2–10mm). The en-bloc resection rate was 93.75% and all patients achieved endoscopically complete resection.

The histologically complete resection was 31.3% in our study.

Multivariate analysis showed that histologically complete resection was associated with tumor size (P = 0.058). Type of procedure for tumor resection was not associated to histologically complete resection rate 9 Patient(56.25%) received endoscopic follow-up once in two years. There was no recurrence in this 9 patients. Endoscopic examination was arranged at a median of 2 months (range 0–24m) after endoscopic resection.

This study had much limitation. We need more data and well experimental design for further study.

Conclusions: Although the en-bloc resection rate was 93.75% in rectal NETs, histologically complete resection rate was 31.3%. Histologically complete resection seems to associated with tumor size. We need more data for further study.

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吳明順 陳俊男 粟發滿 連吉時 陳彥州 1 臺北醫學大學市立萬芳醫院消化系內科 2 臺北醫學大學醫學院消化學科 3 臺北醫學大學醫學院醫學科學研究所

3

Background: Microtubule-targeting agents (MTAs) are widely used in cancer chemotherapy, but the therapeutic responses significantly vary among different tumor types.

Protein kinase RNA-like endoplasmic reticular (ER) kinase (PERK) is an ER stress kinase, and the role of PERK in the anticancer effects of MTAs is still undefined.

Aims: Although MTAs have been applied as cancer therapeutics for several decades, drug resistance is one of the key factors obstructing the clinical applicability of MTAs. Therefore, the antitumor mechanisms of MTAs deserve to be further investigated.

Methods: Four human CRC cell lines, including COLO205, HT-29, HCT-15, and LOVO, were used.

Western blot show phosphorylated PERK protein (Thr980) and FACSan flow cytometer detect G 2 /M arrest and hypodiploid cells.

Results: taxol (TAX) and nocodazole (NOC) significantly induced apoptosis with increased expression of phosphorylated PERK (pPERK; Tyr980) in four human colon cancer cell lines, including HCT-15, COLO205, HT20, and LOVO cells. Induction of G2/M arrest by TAX and NOC with increases in phosphorylated Cdc25C and cyclin B1 protein were observed in human colon cancer cells.

Application of the c-Jun N-terminal kinase (JNK) inhibitors SP600125 (SP) and JNK inhibitor V (JNKI) significantly reduced TAX- and NOC-induced apoptosis and G 2/M arrest of human colon cancer cells. Interestingly, TAX- and NOC-induced pPERK (Tyr980) protein expression was inhibited by adding the JNK inhibitors, SP and JNKI, and application of the PERK inhibitor GSK2606414 (GSK) significantly reduced apoptosis and G2/M arrest by TAX and NOC, with decreased pPERK (Tyr980) and pJNK, phosphorylated Cdc25C, and Cyc B1 protein expressions in human colon cancer cells. Decreased viability by TAX and NOC was inhibited by knockdown of PERK using

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P.146 PERK siRNA in COLO205 and HCT-15 cells. Disruption of the mitochondrial membrane potential and an increase in B-cell lymphoma-2 (Bcl-2) protein phosphorylation (pBcl2; Ser70) by TAX and NOC were prevented by adding the PERK inhibitor GSK and JNK inhibitor SP and JNKI. Conclusions: Activation of PERK and JNK contributes to apoptosis and G2/M arrest by TAX and NOC in human CRC cells.

阿斯匹靈或保栓通對於第二型糖尿病病患 大腸直腸癌的預防效果 EFFECTS OF ASPIRIN OR CLOPIDOGREL ON COLORECTAL CANCER CHEMOPREVENTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

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黃洸偉 官怡君 羅景全 高嘉鴻 1 臺北市北投健康管理醫院, 胃腸科 2 臺北醫學大學- 雙和醫院, 神經內科 3 衛生福利部基隆醫院, 胃腸科 4 中國醫藥大學附設醫院, 核子醫學科 Background: The effect of clopidogrel, whose mechanism of action differs from that of aspirin, on colorectal cancer (CRC) risk remains unknown.

Aims: We investigated the effects of clopidogrel and aspirin, either as monotherapy or combined, on the CRC risk in patients with Type 2 diabetes mellitus (T2DM).

Methods: We conducted a cohort study using Taiwan National Health Insurance Research Database. Four groups comprising 218,903 patients using aspirin monotherapy, 20,158 patients using clopidogrel monotherapy, 42,779 patients using dual antiplatelet therapy, and 281,840 nonuser matched controls were created using propensity score matching. Cox proportional hazards regression was used to evaluate the CRC risk during follow-up.

Results: During the 13-year follow-up period, we found 9,431 cases of CRC over 3,409,522 person-years. The overall incidence rates of CRC were 2.04, 3.45, 1.55, and 3.52 per 1000 person-years in the aspirin, clopidogrel, dual antiplatelet, and nonuser cohorts, respectively. The adjusted hazard ratios (aHRs) were 0.59 (95% confidence interval [CI], 0.56–0.61), 0.77 (95% CI, 0.68–0.87), and 0.37 (95% CI, 0.33–0.40) for the aspirin, clopidogrel, and dual antiplatelet cohorts, respectively. Dose- and durationdependent chemopreventive effects were observed in the three cohorts.

Conclusions: Both aspirin and clopidogrel monotherapies reduced the CRC risk in patients with T2DM in a dose- and duration-dependent manner. The combination of aspirin and clopidogrel was associated with additional benefits.

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P.147

P.148

大部分大腸麟狀上皮細胞癌是轉移性腫瘤 MOST OF COLONIC SQUAMOUS CELL CARCINOMAS ARE METASTATIC TUMORS

第 2 型糖尿病對大腸瘜肉風險的影響 IMPACT OFTYPE 2 DIABETES MELLITUS ON RISK OF COLORECTAL POLYPS

陳俊男 吳明順 粟發滿 連吉時 臺北醫學大學臺北市立萬芳醫院消化內科

許柏格 黃景陽 蘇維文 魏正宗 1 彰化基督教醫院肝膽胃腸科 2 中山醫學大學醫學研究所

Background: The incidence of colon cancer is increasing.

Colon cancer is the leading cause of cancer death. Most of colon cancers are adenocarcinomas, primary colonic squamous cell carcinoma is very rare. Most of colonic squamous cell carcinomas are metastatic tumros.

Aims: Most of colon cancers are adenocarcinomas. Other etioloys such as carcinoid tumors, lymphoid tumors, squamous cell carcinomas are occasionally identified.

An attempt is made to describe the characters of colonic squamous cell carcinoas in our hospital.

Methods: We searched the patients with colonic squamous cell carcinomas in our hospital in recent 20 years. Analysed the number, gender, age of the patients, anatomical location, primary or secondary tumors, what treatments thease patients received.

Results: From 2000 to 2019, there were totally twelve patients with colonic squamous cell carcinomas.Two are men and ten are women. Average age was 62-year-old. The cancer location: two is transverse colon, four is sigmoid colon, three is rectum, three is anus. Two had primary colonic squamous cell carcinomas, three had anal cancer with rectal invasions, seven patients had cervical cancers with colonic invasions.

Conclusions: Primary colonic squamous cell carcinomas is very rare. When we find female patients with colonic squamous cell carcinomas, we must sceen thease patients’ gynecologic condition.

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Background: The incidence rate of type 2 diabetes mellitus (T2DM) and colorectal polyp is getting increasing over the last decades, and the malignancy potential colorectal polyp causes colorectal cancer is an important issue.

Aims: Our study aimed at exploring the relationship betweenT2DM and colorectal polyp and discussed the risk factors of colorectal polyp inT2DM. Methods: we classified T2DM and non-diabetes mellitus (Non-DM) from the Longitudinal Health Insurance Database (LHID) 2000 (a subset of National health Insurance Research with 993,516 people). We classified study individuals into T2DM and Non-DM cohort separately, and used the propensity score matching to balance the baseline profiles among study groups. KaplanMeier cumulative probability curve is used to compared the cumulative risk of colorectal polyp between T2DM and Non-DM groups.

Results: The incidence rate of colorectal polyp in T2DM group after 10.5 years( 126 months) follow upis higher than Non-DM group (aHR 1.29; 95% CI 1.058-1.547). In subgroup analysis of age, below 30 years old persons with T2DM has 124.2% higher than control (aHR 2.242; 95% CI 0.851-5.904). In 30-40 years old group showed T2DM is 38% higher than non-DM group (aHR 1.389; 95% CI 1.119-1.723).

Conclusions: Our results indicated that T2DM persons has relative higher risk of colorectal polyp compared with NonDM persons

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P.149 胃幽門螺旋桿菌根除後是否影響非類固醇 止痛藥劑使用者導致消化性潰瘍疾病的復 發 RECURRENT PEPTIC ULCER DISEASE AFTER HELICOBACTER PYLORI ERADICATION IN PATIENTS RECEIVING NONSTEROIDAL ANTIINFLAMMATORY DRUGS 1

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梁志明 楊世正 吳鎮琨 李育騏 葉文碩 戴維震 1, 2 3 1, 2 吳耿良 許茜甯 蔡成枝 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院 3 長庚醫療財團法人高雄長庚紀念醫院藥劑部 Background: It is well understood that by eliminating Helicobacter pylori (H. pylori) for both primary and secondary prophylaxis effectively decrease ulcer risk among naïve nonsteroidal anti-Inflammatory drugs (NSAID) users. However, it is not evidenced whether the success in killing of these bacteria can help in reducing the recurrence of peptic ulcers in long-term users of NSAIDs, particularly those with a medical record of peptic ulcer disease (PUD). Importantly, very few studies have examined whether the eradication therapy affects the recurrence of PUD in patients receiving a high cumulative defined daily dose of NSAIDs (cDDDs).

Aims: The purpose of this population-based case–control study was to clarify the impact of cumulative dosage of NSAIDs on recurrent peptic ulcers among chronic users after H .pylori eradication.

Methods: We analyzed data of 203,407 adult PUD patients from the National Health Insurance Research Database in Taiwan entered between 1997 and 2013. After matching for age/gender frequencies and the length of follow-up time in a ratio of 1:1, the matched case–control groups comprised 1150 patients with recurrent PUD and 1150 patients without recurrent PUD within 3 years of follow-up.

Results: More recurrent PUDs occurred in NSAID users than in the control group (75.30% vs 69.74%; p = 0.0028).

Independent risk factors for recurrent PUD included patients using NSAIDs [odds ratio (OR): 1.34, p = 0.0040], H. pylori eradication [adjusted OR (aOR): 2.73; p < 0.0001], concomitant H2 receptor antagonist (aOR: 1.85; p < 0.0001) and anti-coagulant (aOR: 4.21; p = 0.0242) use. Importantly, in the initial subgroup analysis, the risk ratio of recurrent PUD did not increase in NSAID users after H. pylori eradication compared with that in non-users

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(p = 0.8490) but a higher risk for recurrent PUD with the increased doses of NSAIDs without H. pylori eradication therapy (aOR: 1.24, p = 0.0424; aOR: 1.47, p = 0.0074; and aOR: 1.64, p = 0.0152 in the groups of ≤28, 29–83, and ≥84 cumulative defined daily doses, respectively).

Conclusions: The current study suggested that H. pylori eradication therapy could decrease the risk of recurrent PUD among patients with high cumulative doses of NSAIDs.

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P.151

「反轉式混和療法」在第一線治療幽門螺旋 桿菌感染上之療效 EFFICACY OF REVERSE HYBRID THERAPY IN THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION

台灣幽門螺旋桿菌感染的流行病學及抗藥 性分析 THE EPIDEMIOLOGY AND ANTIMICROBIAL RESISTANCE ANALYSIS OF HELICOBACTER PYLORI INFECTION IN TAIWAN

施長碧 林德福 1

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吳登強 蔡峯偉 陳文誌 許秉毅 1 中國醫藥大學安南醫院消化內科 2 大千綜合醫院胃腸肝膽科 3 高雄榮民總醫院內科部胃腸肝膽科 4 高雄醫學大學內科部胃腸肝膽科

陳美志 吳明賢 白明忠 方佑仁 陳柏岳 劉志銘 1 臺大醫院 2 臺東馬偕醫院 3 臺大醫院雲林分院 4 嘉義基督教醫院

Background: Reverse hybrid therapy is a simplified hybrid treatment for H pylori infection. It is superior to standard triple therapy and not inferior to bismuth quadruple therapy in the first-line treatment of H pylori infection.

Aims: To investigate the efficacy of reverse hybrid therapy in the first-line treatment of H pylori infection.

Methods: From September 2008 to September 2017, 252 H pylori-infected patients who received 14 days of reverse hybrid therapy (proton pump inhibitor plus amoxicillin for 14 days and clarithromycin plus metronidazole for the initial 7 days) were included in this retrospective cohort study. H pylori status was examined 6 to 8 weeks after therapy. The eradication rate, adverse effects, drug adherence and impacts of antibiotic resistance on eradication efficacy were analyzed.

Results: The intention-to-treat and per-protocol eradication rates of the reverse hybrid therapy were 96.4% and 96.6%, respectively. The frequency of adverse effects was 18.7%, and drug adherence was good (94.4%). The eradication rates of reverse hybrid therapy for H pylori strains with non-resistance, single clarithromycin resistance, single metronidazole resistance and dual resistances were 98.8%, 86.7%, 100% and 87.5%, respectively. Nomogram analysis showed that reverse hybrid therapy can achieve an eradication rate more than 90% when clarithromycin resistance rate of H pylori strains is less than 75%.

Conclusions: Reverse hybrid therapy can achieve a high eradication rate for the first-line treatment of H pylori infection in the areas with clarithromycin resistance rate of H pylori strains less than 75%.

Background: Helicobacter pylori (H. pylori) infection is an important predisposing factor for gastric cancer and peptic ulcer. After improved public sanitation and national policy of H. pylori eradication, some relevant studies showed the prevalence of H. pylori in Taiwan seemed decreasing. The condition of antimicrobial resistance for H. pylori infection became more severe by time in the world.

However, the updated nationwide prevalence of H. pylori infection and survey of antimicrobial resistance in Taiwan are lacking.

Aims: We aimed to assess the updated prevalence of H. pylori infection and change of antimicrobial resistance for H. pylori infection in Taiwan.

Methods: We recruited adult volunteers who never received H. pylori eradication. The eligible participants received C13 urease breath test (C13 UBT), H. pylori stool antigen (HpSA) and serology H. pylori antibody (HpAb) for screening of H. pylori infection to find the prevalence of H. pylori infection in Taiwan. We also recruited children and adolescent to receive C13 UBT and HpSA for screening of H. pylori infection.

On the other hand, adult patients who visited hospital for upper endoscopic exam were invited for antimicrobial resistance study. Eligible patients receive biopsy of gastric mucosa for histological exam, rapid urease test and culture of H. pylori. The agar dilution method is used to identify the minimum inhibitory concentration of antibiotics, and the point mutations of 23S rRNA and gyrase A were also detected.

Results: Between Jan 1, 2019 and Dec 20, 2019, 732 asymptomatic subjects, 203 of whom were adolescents/ children and 529 were adults, were enrolled for the prevalence study. Using the diagnostic tool with 13C-UBT, we found that 21.5% (151/701) of participants were H. pylori-positive cases, including 26.5% (133/502) for adults

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P.152 and 9.1% (18/199) for adolescents/children. The agestandardized prevalence of H. pylori infection was 27.5% in asymptomatic adults after adjustment of the population structure in Taiwan. Besides, 162 strains were collected in 2019 for resistance analyses. The phenotypic resistance with the agar dilution method for Clarithromycin, Metronidazole, Amoxicillin, Levofloxacin and Tetracycline were 17.6%, 22.8%, 1.9%, 16.5%, and 5.7%, respectively.

The genotypic resistance analyses of gastric mucosal biopsy showed that the point mutations of 23S rRNA and gyrase A were 21% (34/162) and 18% (29/161), respectively.

Conclusions: The study showed that the prevalence of H. pylori infection has decreased in Taiwan, but the antimicrobial resistance (Clarithromycin and Levofloxacin) has slightly increased. The prevalence rates of H. pylori infection and antimicrobial resistance were different in different districts of Taiwan. It is advisable to develop screening and treatment protocol in various regions according to local conditions.

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高劑量二合療法在第一線幽門螺旋桿菌除 菌治療之療效 TWO-WEEK HIGH-DOSE DUAL THERAPY FOR PATIENTS WITH TREATMENT-NAïVE HELICOBACTER PYLORI INFECTION – A SINGLE HOSPITAL EXPERIENCE IN TAIWAN 王大維 李嘉龍 洪志聖 涂天健 江技坤 黃鼎鈞 臺北國泰綜合醫院胃腸科 Background: Although clarithromycin resistance of Helicobacter pylori in Taiwan is relative low (11.2%), the eradication rates of two-week triple therapy is not satisfactory in Northern Taiwan. Given that amoxicillin is associated with lower resistance and is effective at high (>5.5) pH environments, we conducted a high-dose proton pump inhibitor and amoxicillin as first-line therapies in eradicating Helicobacter pylori at one single hospital in Taiwan.

Aims: To observe the effectiveness of 2-week highdose dual therapy as first-line therapies in eradicating Helicobacter pylori infection at one single hospital in Taiwan Methods: We collected data from January 2019 to December 2019 to evaluate the efficacy of a high-dose dual therapy(HDDT; rabeprazole 20 mg, amoxicillin 750 mg 4 times daily for 14 days). H pylori infection was mostly examined by using the 13C-urea breath test (One for H. pylori stool antigen test; another two for Campylobacterlike organism test). The rates of adverse effects, compliance, and eradication were evaluated.

Results: A total of 162 patients with treatment-naive H. pylori infection received high-dose dual therapy. The mean age was 54.56±10.3 years old and 72 (44.4%) were males.

The eradication rates for high-dose dual therapy were 63.6% (103/162) in intention‐to‐treat analysis; and 84.4% (103/122) in per‐protocol analysis. The adverse event rates were 12.9% (21/162).

Conclusions: A 14-day rabeprazole and amoxicillincontaining high-dose dual therapy is not more effective as traditional triple therapy but less adverse effect in patients with treatment-naive H. pylori infection in Taiwan.

2020 消化系聯合學術演講年會

P.153 內視鏡超音波導引下於左腎上腺病變執行 細針穿刺 ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION OF LEFT ADRENAL LESIONS 林連福 黃彼得 肝膽腸胃科, 內科部, 童綜合醫院

EUSGFNA smear cytology, cell block, and pathology were positive for Cryptococus. This patient also has Cryptococal meningitis. Both patients with fungus infection presented with adrenal insufficiency. There were no complications with EUSGFNA. Conclusions: EUSGFNA of left adrenal gland is safe with good results.

Background: Enlarged adrenal glands can be due to various causes [Endocrine Connections 2016;5: 92– 100].

Tissue procurement performed percutaneously using either US or CT has traditionally been the modality of choice, with the yields of non-diagnostic samples in up to 14% of patients and is associated with adverse events in 0.412% [Am J Roentgenol 2009;193:1686-1690. J Med Liban 2011;59:173-175. Am J Gastroenterol 2011;106:18621863. J Ultrasound Med 2008;27:261-267.]. Endoscopic ultrasound guided fine needle aspiration (EUSGFNA) of adrenal gland offers a less invasive and more accurate method for sampling the adrenals with a few side effects and complications [Hippokratia 2008;12:37-42, Annals of Gastroenterology 2016; 29: 307-311] Aims: To report the experience of EUSGFNA of left adrenal gland.

Methods: Bwteen June 2008 and August 2019, five cases of EUS-guided FNA of left adrenal gland were analyzed retrospectively. The inclusion criteria include: (1) symptomatic left adrenal gland enlargement like upper abdominal pain, anorexia, body weight loss; (2) no bleeding tendency. The exclusion criteria were: (1) Right adrenal gland lesion; (2) patient refused to undergo EUSGFNA. Olympus UCT 2000 (Olympus Optical Co., Ltd., Tokyo, Japan) linear echoendoscope, Wilson Cook medical needle 22 G were used. Color Doppler was applied to avoid puncturing vessels, and three to four passes were performed with negative pressure of 10cc. Smear cytology, cell-block, and histology, with culture when needed.

Results: There were 5 patients (3 female, and 2 male), with a mean age of 76 (61-92 years). Two had bilateral adrenal enlargement. The mean size of left adrenal gland was 1.42 (1-2.5cm). The mean number of passes of aspiration was 3.4 (3-4). The first case was lung adenocarcinoma with adrenal metastasis, the 2nd and 3rd cases were adrenal hyperplasia.

The 4th case was an isolated adrenal Histoplasmosis. In the 5th case, EUSGFNA aspirate mixed with little normal saline was positive for Crytpococcal antigen with high titer (1:1024), which has not been reported in the literature. The

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P.154

P.155

新型口服抗凝血劑與維生素 K 拮抗劑在亞 洲心房震顫患者的消化道出血風險：統合分 析 GASTROINTESTINAL BLEEDING RISK OF NOVEL ORAL ANTICOAGULANTS VERSUS VITAMIN K ANTAGONIST IN THE ASIAN ATRIAL FIBRILLATION PATIENTS: A META-ANALYSIS

消化道內視鏡夾與核磁共振檢查之相關安 全性 IS IT SAFE WHEN ENDOCLIPS IN THE ALIMENTARY TRACT UNDER MAGNETIC RESONANCE IMAGING EXAMINATION?

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楊光祖 孫煒智 蔡騌圳 蔡峯偉 陳文誌 許秉毅 1 高雄榮總內科部胃腸肝膽科 2 國立陽明大學

Background: Novel oral anticoagulants (NOACs) are widely used for preventing embolic events resulted from atrial fibrillation (AF). Plenty of studies had compared NOACs with vitamin K antagonist (VKA or warfarin) in effectiveness and safety. However, gastrointestinal bleeding (GIB) risk is still not clarified in Asian AF patients.

Aims: The aims of this study are to investigate GIB risk of NOACs compared with VKA for the Asian AF population and to understand which NOAC is safer in GIB safety.

Methods: A systematic search of studies for NOACs, VKA, and the Asian AF patients was conducted mainly in PubMed, Embase, Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov. We used the random model hazard ratio (HR) of any GIB from overall NOACs in reference to VKA as the primary outcome. Different kind of NOACs compared with VKA in GIB safety comprised the secondary outcome.

Results: This meta-analysis recruited two randomized controlled trials (RCT) and four retrospective studies, more than 200,000 participants in total. The primary outcome revealed a lower HR of GIB risks in overall NOACs in reference to VKA in the Asian AF population. (HR: 0.645; 95% CI: 0.552 to 0.753; p < 0.001). Besides, the GIB risk of apixaban is the lowest (HR: 0.438). The other three NOACs showed edoxaban (HR: 0.650), dabigatran (HR: 0.700), and rivaroxaban (HR: 0.747) for GIB risk.

Conclusions: NOACs apparently cause less GIB risk than VKA in the Asian AF patients. Furthermore, Apixaban is the safest in our data analysis. Future real-world studies and RCTs should be performed to evaluate the GIB risk of NOACs.

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王程毅 林煊淮 黃信閎 張維國 施宇隆 謝財源 1 國軍高雄總醫院內科部肝膽腸胃科 2 三軍總醫院內科部肝膽腸胃科 3 臺北振興醫院內科部肝膽腸胃科

2

Background: Not all endoscopic clips were Magnetic Resonance Imaging (MRI) compatible. Before the patient received MRI examination, screening of endoscopic clips was recommended. However, there were some patients who underwent MRI scans with endoscopic clips in the alimentary tract accidentally. Only a few case reports showed it might relate to bleeding, clip migration, organ perforation, or artifact of image, but there was no serial study on this issue.

Aims: We aimed to study the complication and safety of the patients who had endoclips in the alimentary tract, and then received MRI examination within one month.

Methods: A retrospective study recruited the patients who had endoclips in the alimentary tract, and then received MRI examination within one month at Tri-Service General Hospital between April 2014 and April 2019. The endoscopic clip was Olympus Long Clip HX-610-090L, and it’s non-MRI-conditional. Clinical parameters, the indication and site of endoscopic clips, the duration time of MRI procedure, and complications were recorded from medical records.

Results: Between April 2014 and April 2019, there were 23 patients who had done endoscopic clips first and then received MRI examination within one month. Their mean age 64.1 years (± 13.7 years) and 16 were males. 9 patients had used anti-coagulation or anti-platelet agents during the examination. The indication for endoclips was mucosal/ submucosal defect < 3 cm (4 cases); bleed (7 cases); polyps < 1.5 cm in diameter (11 cases); luminal perforation < 2 cm (4 cases). The average days to receive MRI examination was 9.79 days (± 7.87 days). The duration time of MRI procedure was 23 mins (± 10mins). The location of endoclip and site of MRI scan were shown in Table 1.

Almost patients received MRI examination under 1.5 Tesla (only 3 patients obtained 3 Tesla for brain MRI scan). The complication of dislocation of endoclip occurred in one

2020 消化系聯合學術演講年會

P.156 patient and artifact in four patients (Table 2). There were no patient developed re-bleed, perforation, or death.

Conclusions: According to our study, there was no lethal complication such as perforation, or death. There was one patient developed endoclip dislocation and four with artifact imagines (Figure 1,2). Hence, it seems to us that the endoscopic clips which we used might be safe for MRI scan even with endoclip was still in the alimentary tract.

However, our case number was not enough to draw the conclusion that it was totally safe during this situation.

嗜伊紅性腸炎臨床經驗與小腸鏡表徵之回 溯性研究 THE CLINICAL AND ENTEROSCOPIC FEATURES OF EOSINOPHILIC ENTEROTITIES IN A RETROSPECTIVE STUDY 許貝池 周仁偉 吳宜樺 中國醫藥大學附設醫院消化系 Background: Gastrointestinal eosinophilic disorders are a group of enterotities that include eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis and all of them characterized by mucosal infiltration of eosinophils and associated with digestive symptoms, after exclusion of other secondary causes.Eosinophilic gastroenteritis is a rare disease that eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes. The epidemiology, pathophysiology and evidence of effective treatments of eosinophilic gastroenteritis are developing based on limited case reports and small uncontrolled case series.

Aims: To evaluate the clinical and enteroscopic features of eosinophilic enteritis in a retrospective study of patient receiving enteroscopy at a medical center in mid-Taiwan Methods: From May 2012 to December 2019, we retrospectively collected patients diagnosed with eosinophilic enteritis at China Medical University Hospital in mid-Taiwan. Diagnosis of eosinophilic enteritis requires three criteria, namely: (1) presence of gastrointestinal symptoms; (2) histologic evidence of eosinophilic infiltration ( more than 15 eosinophils per HPF )in one or more areas of the small bowel; and (3) exclusion of other causes of tissue eosinophilia. The gender, ages, peripheral eosinophils, initial symptoms, enteroscopic findings, pathological findings, abdominal computed tomography, ultrasound, rates of glucocorticoid use, and relieving rate after treatment of all patients were analyzed.

Results: The gender ratio was 8 males to 3 females, and the mean age was 49.1 years. All patient had received Esophagogastroduodenoscopy and revealed nonspecific chronic gastritis and gastric ulcers. In 18% of the patients had peripheral eosinophilia. The enteroscopic features of eosinophilic enteritis revealed edematous and reddish mucosa (80%). In 34% of all patients had obvious wall thickness of small intestine in abdominal computed tomography. The total rate of glucocorticoid use was 91%.

Ten patients receiving glucocorticoid (10-40 mg/day) had

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P.157 mild to well response and 6 patients need long-term (> 12 months) therapy with titration.

Conclusions: Most of the patient (91%) with eosinophilic enteritis had abdomen pain initially. The enteroscopic features of eosinophilic enteritis revealed slightly edematous and reddish mucosa. At present, systemic steroids were the mainstay of treatment for eosinophilic enteritis.

經切片證實為非酒精性脂肪肝的患者的腸 道菌象失衡：南臺灣的一項前瞻性橫斷面研 究 GUT DYSBIOSIS IN PATIENTS WITH BIOPSY-PROVEN NONALCOLIC FATTY LIVER DISEASE: A PROSPECTIVE CROSS-SECTIONAL STUDY IN SOUTHERN TAIWAN 1

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蔡明釗 陳肇隆 劉毓寅 王植熙 顏毅豪 蔡成枝 1 胡琮輝 1 高雄長庚紀念醫院胃腸肝膽科 2 高雄長庚紀念醫院一般外科

Background: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide.

Although gut microbiota plays a role in NAFLD, data about gut dysbiosis in human NAFLD remains scarce in the literature, especially in Asian.

Aims: We aimed to analyze microbiomes of adults with and without NAFLD. Methods: We performed a prospective, observational, cross-sectional study of adults with histology-proven NAFLD (nonalcoholic fatty liver [NAFL], n = 25; nonalcoholic steatohepatitis [NASH], n = 25) and living liver donors as healthy controls (n = 25) from Kaohsiung Chang Gung Memorial Hospital, Taiwan. The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples.

Results: NAFLD patients had higher BMI, cholesterol, triglyceride, and HbA1C level, and were more likely to have diabetes and hypertension than healthy controls.

Lachnospiraceae and Ruminococcaceae abundance were significantly decreased in NASH patients compared with healthy controls. In NAFLD group, NASH patients had higher abundance of Prevotellaceae and Veillonellanceae but lower abundance of Lachnoclostridium than NAFL patients. This study limited by a small sample size, a food questionnaire, and variations in age composition that my influence differences in the composition of gut microbiota.

Conclusions: Through fecal microbiome analysis, we associated NAFL and NASH with gut dysbiosis. Future larger studies, including those with populations stratified by age and dietary habits, are required to confirm this.

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P.159

局部的放射治療可提高系統性的免疫力及 癌細胞的清除能力 ENHANCEMENT OF SYSTEMIC IMMUNE SURVEILLANCE AND TUMOR ELIMINATION BY REGIONAL RADIOTHERAPY

胃腸胰神經內分泌瘤臨床病理表現：北台灣 單一醫學中心經驗 CLINCO-PATHOLOGIC CORRELATION IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOURS (GEPNETS): A REAL WORLD EXPERIENCE IN SINGLE MEDICAL CENTER IN TAIWAN

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劉宗達 黃文彥 樊修龍 施宇隆 謝財源 黃瑋琛 1 三軍總醫院胃腸肝膽科 2 三軍總醫院放射腫瘤部 3 三軍總醫院移植外科 4 胃腸科臨床免疫實驗室

Background: Regional radiotherapy (RR), an important anti-tumor treatment for more than half of solid cancers, can induce tumor regression beyond the radiation sites through an immune-mediated abscopal response.

Aims: The study is designed to understand whether conditioned medium of an irradiated tumor could enhance the cytotoxic ability of immune cells, even when they reencounter tumor cells.

Methods: ICC and flowcytometry were used in this study.

Results: ICC results revealed caspase-3 protein was induced in these two cell lines. The flowcytometry data further illustrated the radiation can significantly induce tumor cell death in both apoptosis and necrosis pathways.

Second, PBMC (Peripheral Blood Mononuclear Cell, PBMC) isolated from healthy controls were cultured in conditioned medium of irradiated tumor cells. The following flowcytometry data demonstrate the changes of phenotypic and functional markers of NK and T cells by conditioned medium Conclusions: These results suggest irradiated cancer cells can release certain immune modulators to influence cellular immunity. Furthermore, the cytotoxicity of NK and T cells will be evaluated in the next step to verify the enhancement of tumor elimination.

蔡宗憲 章振旺 陳銘仁 朱正心 王鴻源 馬偕紀念醫院腸胃內科 馬偕醫護管理專科學校 馬偕醫學院 Background: Neuroendocrine tumors are rare neoplasms, but the incidence has increased related to improved diagnostic method, including EUS and endoscopy.

According to a population based study in the US (SEER), the annual incidence has increased about 5 times from 1973 to 2012, and gastroenteropancreatic origin is most common. However, there has been a paucity of data to comprehensively describe the clinical characteristics of NETs among Asians.

Aims: This study analyzed the incidence rate and the observed survival rate of NETs in a single medical center in Taiwan.

Methods: A retrospective study in Mackay Memorial Hospital, Taipei, Taiwan was performed for analysis for patients diagnosed with Gastroenteropancreatic neuroendocrine tumours with pathologic proof with tissue biopsies or surgical resection specimen. The analysis was done including overall survival, demographics, and treatment.

Results: From Jan 2013 to Dec 2018, there are 183 patients were diagnosed with Gastroenteropancreatic neuroendocrine tumours, including 24 in stomach, 8 in small bowels, 14 in colon and appendix, 100 in rectum, 30 in pancrease, 1 in esophagus, and 6 in unknown origin with liver and peritoneal metastases. Rectal NETs showed most common site in our medical center, which is different compared to SEER data in the U.S, which may be related to health policy in Taiwan and most patients are asymptomatic (52%), in WHO G1 grading, and incidentally found. The poorest survival outcome is in pancreatic NET in our data, which showed mean overall survival about 16.39 ± 16.26 months. However, most of pancreatic NETs are asymptomatic until liver or distant metastases, and the ratio of poorly differentiated tumors

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P.160 are most common in pancreatic NET, which reflect the slow growth rates and asymptomatic in the initial stage of disease. There is only one esophageal neuroendocrine tumour in our medical center, which was misdiagnosed as esophageal adenocarcinoma at beginning and received total esophageectomy and gastric tube and diagnosed as G1 NET. He had survived more than 5 years after tumor resection until tumor recurrence with lymph node metastases. For gastric, small intestinal, and colonic NETs, tumor resection for G1 NET without lymph node and distant metastases had best survival outcomes, either with surgery or endoscopic resection.

Conclusions: Compared to the data of Norway and the US, the age-standardized incidence rate of NETs in Taiwan is lower. There is difference in popularity in organ systems where rectal NETs are most common in Taiwan, which may be related to health policy. Further studies on the pathogenesis of NETs are warranted to devise preventive strategies and improve treatment outcomes for NETs.

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Enteropathy-Associated T Cell Lymphoma (EATL)： 20 年內在單一醫學轉診中心之病 人照顧經驗 ENTEROPATHY-ASSOCIATED T CELL LYMPHOMA (EATL): 20YEAR EXPERIENCE IN A TERTIARY REFERRAL CENTER 1

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3

3

1

葉琬智 周文堅 孫家棟 尤善琦 凃佳宏 鄭祖耀 1 國立臺灣大學醫學院附設醫院內科部 2 國立臺灣大學醫學院附設醫院檢驗醫學部 3 國立臺灣大學醫學院附設醫院病理部

1,2

Background: Enteropathy-associated T cell lymphoma (EATL) is a rare primary gastrointestinal lymphoma. Among the primary gastrointestinal lymphomas, B cell lymphomas account for a higher percentage, while the T cell lymphomas account for a small part. EATL is frequently associated with gluten sensitive enteropathy (type I EATL) in the western countries, but the monomorphic variant (type II EATL) predominates in Asian countries where celiac disease is rare.

Aims: Since there was only some small case series on reviewing previous literature, we would like to analyze the EATL cases in our institution.

Methods: We retrospectively reviewed the patients with histopathology diagnosis of EATL in our hospital, National Taiwan University Hospital, from 1998 to 2018.

Results: In this study, most cases of primary small intestine lymphoma were B cell lymphoma, and diffuse large B cell lymphoma (DLBCL) was the most common type (43%).

There were fewer primary small intestine T cell lymphomas.

EATL accounted for only 9%, while NK/T cell lymphoma accounted for 3%. EATL more frequently developed in adults (mean age: 57.4), and the male-female sex ratio was about three. Almost all EATL cases had jejunal involvement, and the most common symptoms were abdominal pain and diarrhea. EATL had poor prognosis, and most of the EATL patients died within the first year of diagnosis. The median survival time of EATL, NK/T cell lymphoma, and DLBCL were 12 months, 1 month, and 35 months respectively in comparison analysis. Two EATL patients were still in complete remission status, and other 11 patients had passed away.

Conclusions: EATL is a rare primary gastrointestinal lymphoma and has poor prognosis. The chemotherapy response was usually not good. High-dose chemotherapy with autologous stem cell transplantation may provide a better outcome.

2020 消化系聯合學術演講年會

P.161 ABO 血型與潰瘍性結腸炎之相關性：一中 台灣醫學中心之回溯性研究 THE ASSOCIATION OF ABO BLOOD GROUPS AND ULCERATIVE COLITIS: A RETROSPECTIVE STUDY IN MIDTAIWAN 1

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賴香君 吳宜樺 周仁偉 鄭庚申 蔡元耀 陳宗偉 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消化內科 3 中國醫藥大學附設醫院大腸直腸外科 4 中國醫藥大學附設醫院病理部

We analyzed the characteristics of UC patients between the diagnostic age older or younger than 40 years. However, there were no significantly statistical difference between two age groups (Table 4).

Conclusions: ABO blood groups were not associated with the prevalence of UC, although blood type A UC patients had the higher prevalence in our current study compared to the general populations with blood type A. Blood type O UC patients had higher baseline ESR level and blood type A UC patients had higher baseline hemoglobin level.

Background: The variations in ABO blood groups are reported to be associated with multiple disorders.

Ulcerative colitis (UC) is a chronic and relapsing disease of the gastrointestinal tract with unclear etiology. The incidence and prevalence of UC are low but increasing in Taiwan Aims: The aim of our current study was to investigate the distribution of ABO blood groups in patients with UC and to explore its impact on disease severity.

Methods: From January 2000 to December 2019, we retrospectively collected patients diagnosed as UC in our hospital, a tertiary referral center in central Taiwan. Clinical characteristics of patients with UC including gender, age at diagnosis, ABO blood groups, disease phenotype and behavior, operation rate and baseline laboratory data were collected.

Results: A total of 130 patients with UC were enrolled to our present study (Table 1). Male patients accounted for the predominance of all patients (63.1%). The mean diagnostic age of all UC patients was 39.2 years. Of 130 UC patients, 43 (33.1%) were blood type O, 41 (31.5%) were blood type A, 39 (30.0%) were blood type B, and 7 (5.4%) were blood type AB. However, there was no significant association between the ABO blood groups and UC patients compared to the general population of Taiwanese (p = 0.1906) (Table 2). In the subgroup analysis of different blood types, there were no significant difference of disease locations and operation rates between these groups. Moreover, blood type A UC patients had higher hemoglobin level compared to blood type O UC patients (13.31 g/dL vs 12.30 g/dL, p = 0.0347). Blood type A UC patients had lower erythrocyte sedimentation rate (ESR) level compared to blood type O UC patients (12.46 mm/hour vs 21.5 mm/hour, p = 0.0288).

Blood type O UC patients had the highest ESR level compared to non-O UC patients (p = 0.0228) (Table 3).

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2020 消化系聯合學術演講年會

P.162 單氣囊小腸鏡之於測量小腸型克隆氏症疾 病活動程度：一所台灣醫學中心的臨床經驗 SINGLE-BALLOON ENTEROSCOPY FOR MEASURING DISEASE ACTIVITY IN SMALL-BOWEL CROHN’S DISEASE: CLINICAL EXPERIENCE OF A TERTIARY MEDICAL CENTER IN TAIWAN 陳保中 陳鵬仁 林榮鈞 楊志偉 林煊淮 黃瑋琛 黃信閎 施宇隆 張維國 謝財源 黃天祐 三軍總醫院 Background: Knowing disease activity of small-bowel Crohn’s disease (CD) accurately remains a major challenge.

Several clinical scores, such as Crohn’s disease activity index (CDAI) or Harvey-Bradshaw index, have developed to access the severity of CD. However, these grading systems have been criticised for being inconvenient, prone to inter‐observer variability, poorly reproducible and insensitive to change over time.

Aims: Recent researches in CD suggest the use of endoscopic scores in clinical practice because they have prognostic value. With the introduction of device-assisted enteroscopy (DAE), it is available to approach the midgut.

The aim of our study is to evaluate the role of singleballoon enteroscopy (SBE) in measuring disease activity of small-bowel Crohn’s disease.

Methods: Eleven CD patients with negative esophagogastroduodenoscopy and colonoscopy underwent SBE at our institution between September 2009 and August 2019. Their characteristics, CDAI and endoscopic severity scale of small bowel CD were collected and retrospectively analyzed.

Results: Among our cases, 7 were male and 4 were female. The mean age was 57.5±18.0 years. The average duration of symptoms between onset and diagnosis was 7.45 months. About half of the patients (45.4%) has cigarette smoking. There was absence of familial tendency (0%). Abdominal pain was the most common presenting symptom (81.8%), followed by weight loss (36.3%). The most frequently involved location was ileum (63.6%), followed by jejunum (27.2%) and duodenum (9.2%).

Four stricturing disease, one penetrating disease, and six nonstricturing, nonpenetrating disease were depicted. The proportion of CDAI 150-220, CDAI 220-450 and CDAI >450 was 27.2%, 27.2% and 45.6%. Most SBE findings of small bowel CD were aphthous ulcer, longitudinal ulcer

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and stricture. The endoscopic severity scale of small bowel CD were mostly score 3 and 4.

Conclusions: Our retrospective research provide further information on the clinical characteristics and endoscopic presentation of small-bowel CD in Taiwan. Additionally, we find there is discrepancy between the clinical and endoscopic scores in measuring disease activity of smallbowel Crohn’s disease.

2020 消化系聯合學術演講年會

MEMO

2020 消化系聯合學術演講年會

MEMO

2020 消化系聯合學術演講年會

MEMO

2020 消化系聯合學術演講年會

MEMO