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Breakthrough Papers in Hepatology in 2011 GI Hepatology Update 2012 Marco Lacerda


GENERAL HEPATOLOGY


• Individuals with PSC and UC are at higher risk for colorectal neoplasia • Retrospective studies have shown mixed results • High-dose UDCA (28-30) increased SAE in PSC


High-dose UDCA and colon cancer • Methods: • Patients with UC/PSC previously enrolled in a high dose UDCS trial were analyzed • 56 patients; 25 UDCA; 31 placebo • Mean time – 4.4 y • Results of surveillance colonoscopy and pathology analyzed


High-dose UDCA and colon cancer • Results • 9 of 25 (36%) of UDCA patients developed neoplasia (1 ca, 1 high-grade, 7 low-grade) • 3 of 31 (9.7%) of placebo patients developed neoplasia (1 ca, 1 high grade, 1 low grade) • Hazard risk 4.4; p=0.02


High-dose UDCA and colon cancer • Conclusion • Long term use of high-dose UDCA in patients with PSC/UC is associated with increased risk of colorectal neoplasia


• Although ¼ of patients with cirrhosis develop PVT, best treatment option is not clear; • Anticoagulation advocated for recent clots; • Small studies suggested efficacy of TIPS


TIPS for Portal vein thrombosis • Retrospective study of cirrhotic patients with non-tumoral PVTs receiving TIPS; • No anticoagulation was used. • 70 patients (67% males, mean age 55) • Mean Child’s score: 7.9; MELD 11.6; • Hepatitis C – 53%; • Decompensated portal hypertension was the indication in 94%


TIPS for Portal vein thrombosis • At mean f/u of 24 mo: • 57% had complete recanalization; • 30% had decreased thrombosis; • 13% had no improvement.

• Of the patients with complete recanalization 97% maintained it for mean of 20.7 mo; • Survival: • 99% 1 mo • 89% 12 mo • 81% 24 mo


TIPS for Portal vein thrombosis • Conclusion: • For non-tumoral PVT TIPS was safe and effective in > 50% for at least 2 years; • Concerns: • No control group • Relatively small group


• Steroids are treatment of choice for severe ETOH hepatitis; however: • 6 mo mortality approaches 65%


Steroids plus NAC in severe ETOH hepatitis

• Objectives and method • 6 months survival of 174 patients with severe ETOH hepatitis (Maddrey >32), randomized to receive steroids with or without NAC • All patients received 40 mg prednisone 28 d; • NAC group received IV infusion for initial 5 d


Steroids plus NAC in severe ETOH hepatitis

• Conclusion: • Improved one month survival and development of HRS however; • No improvement in primary outcome – overall survival at 6 months


Early liver transplantation for severe alcoholic hepatitis • Studied the result of early OLT (<6 mo sobriety) on 6 months survival of patients with severe alcoholic hepatitis • Admission criteria were • • • • •

Maddrey >32; No prior episodes of alcoholic hepatitis; Non-response to medical therapy (Lille >0.45); Adequate family support No psychiatric co-morbidities and strong commitment


Early liver transplantation for severe alcoholic hepatitis • • • •

26 patients Mean Lille score 0.88 Mean non-response time 13 days Fewer than 2% of admitted patients were selected • 2.9% of grafts were used


Results â&#x20AC;˘ 26 patients. 6 mo survival was higher than matched, non-randomized 26 controls (77 vs 23%, p<0.001) â&#x20AC;˘ 3 patients resumed drinking: at 720, 740 and 1140 days after transplant

Conclusion: â&#x20AC;˘ Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy


HEPATIC ENCEPHALOPATHY


• 299 patients with recurrent HE • (140 drug /159 placebo)

• At least 2 previous episodes; in remission • Rifaximin 550 bid 6 mo • End point • Primary: time to 1st breakthrough HE • Secondary: time to 1st admission due to HE


Minimal Hepatic Encephalopathy • Not obvious cognitive deficits • Impaired quality of life • Difficult diagnosis, based on neuropsychometric and neuropsychological • Patients with MHE have little or no insight into their condition, especially their ability to drive


â&#x20AC;˘ Legal ramifications not yet evaluated â&#x20AC;˘ Reviewed all 50 states BMVs regulations and requirements for physicians to report potentially impaired drivers â&#x20AC;˘ Reviewed legal databases in search for lawsuits against physicians or patients related to HE


Driving and MHE • Few (6) states have regulations mandating physicians to report; 25 grant immunity for reporting • Minimal HE would not fit criteria for medical impairment for overt signs and symptoms are not present • No lawsuits were identified against physicians / patients related to HE • However…


Red journal suggests standardized evaluation


â&#x20AC;˘ 94 patients received either rifaximin 400 mg or placebo tid for 8 weeks â&#x20AC;˘ More patients receiving rifaximin achieved reversal of MHE (75.5% vs. 20% p<0.0001)


â&#x20AC;˘ Similar, 42 patients currently driving, received either rifaximin 550 mg or placebo bid, 8 weeks. â&#x20AC;˘ Percent reduction in total driving errors higher in treatment group (76% vs. 31%, p=0.013)


Rifaximin and MHE • Conclusions: • Rifaximin significantly improves both cognitive functions and HRQOL in patients with MHE. • Patients with MHE significantly improve driving simulator performance after treatment with rifaximin, compared with placebo


NASH


• TZDs and antioxidants can lead to improvements in NASH • Phase III, multicenter, double blind trial • 247 nondiabetic NASH • Pioglitazone (30 mg daily) • Vitamin E (800 IU daily) or • Placebo • 96 weeks


NAFLD â&#x20AC;&#x201C; spectrum from benign steatosis to necroinflamatory changes and fibrosis; Prevalence up to 39% Progressive disease in approximately 15% No definitive pharmacological treatment available


Atorvastatin plus vit E and C for Nash • 1,005 patients, both sexes, randomized to • Atorvastatin 20, vitamin C 1 g and vitamin E 1,000 IU vs. • Placebo, matching

• CT scan Liver to spleen (LS) ratios were calculated on 455 patients at baseline and follow-up • Mean duration of follow-up was 3.6 years


Results • 80 patients had NAFLD at baseline • Baseline triglyceride (OR) = 1.003, P < 0.001) and BMI (OR = 0.10, P < 0.001) were independent predictors of NAFLD. • Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up, 70 vs. 34 % (OR = 0.29, P < 0.001). • 3 patients had increase in aminotransferases; after 2 years, levels improved in 2 of 3.


Conclusions • Atorvastatin plus vitamins C and E lowered the risk of moderate-to-severe hepatic steatosis by 70 % in a healthy population of 80 patients with NAFLD at baseline after 4 years of therapy. • Study limitations: • Difficult to determine which of the cocktail medications is/are active • Measurement of steatosis is not gold standard • Not evaluated in patients with significantly abnormal liver enzymes


VIRAL HEPATITIS


Conclusions • Response-guided telaprevir combination treatment for HCV infection – NEJM Sept 2011 • Telaprevir alone or with Peg-Riba reduces HCV RNA in patients with geno 2 but not 3 – Gastro Jun 2011 • Telaprevir for previously treated and untreated HCV infection. NEJM Mar 2011 • Telaprevir for previously treated and untreated HCV infection. NEJM Jun 2011


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