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Management of Alcoholic Hepatitis and Cirrhosis

Management of Alcoholic Hepatitis and Cirrhosis. W. Ray Kim, MD Gastroenterology and Hepatology Stanford University School of Medicine. Total Adult Per Capita Alcohol Consumption ( liters). Per Capita Alcohol Consumption per Drinker. (2005). Problematic Drinking. Epidemiologic Definitions

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Management of Alcoholic Hepatitis and Cirrhosis

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  1. Management of Alcoholic Hepatitisand Cirrhosis W. Ray Kim, MD Gastroenterology and Hepatology Stanford University School of Medicine

  2. Total Adult Per Capita Alcohol Consumption (liters)

  3. Per Capita Alcohol Consumption per Drinker (2005)

  4. Problematic Drinking • Epidemiologic Definitions • Binge drinker: Five or more drinks on one occasion • Heavy drinker: • Adult men having more than two drinks per day • Adult women having more than one drink per day

  5. DSM-IV Definitions Abuse: • Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, home • Recurrent substance use in situations in which it is physically hazardous • Recurrent substance-related legal problems • Continued substance use despite having persistent or recurrent social or interpersonal problems Dependence: Abuse accompanied by 1. Compulsive drinking behavior 2. Tolerance 3. Withdrawal

  6. Cirrhosis HCC Alcoholic Liver Disease Abuse/ Dependence ALD All Drinkers Heavy/Binge Drinkers

  7. Alcoholic Liver Disease Steatosis Alcoholic Hepatitis Cirrhosis /Steatohepatitis

  8. Importance of Abstinence Survival after Dx of Cirrhosis Survival after Decompensation n=278 n=233 Powell and Klatskin, 1968

  9. Pharmacotherapy of Alcoholism

  10. Pharmacotherapy of Alcoholic Fibrosis/Cirrhosis

  11. Alcoholic Hepatitis • Syndrome consisting of • Excessive alcohol consumption • Typical clinical presentation: jaundice, anorexia, fever, tender hepatomegaly • Moderately elevated aminotransferase (100-300U/L) with higher AST than ALT (AST/ALT>2) • Exclusion of other causes of acute and chronic liver disease. • Spectrum: Mild injury to severe, life-threatening injury • Acute on chronic damage: • 10%-35% of hospitalized alcoholic patients • Concomitant cirrhosis in more than 50%

  12. Corticosteroids • Re-analysis of 3 previous RCTs • Selecting patients with MDF < 32 (n=205) • Prednisolone 40mg qd x 28 days Mathurin. J Hep 2002;36:480, Mendenhall. NEJM 1984;311:1464, Carithers. Ann Intern Med 1989;110:685, Ramond. NEJM 1992;326:507

  13. Pentoxyfylline Single center RCT (n=101) • Severe AH (MDF > 32) Pentoxyfylline (400 mgs tid) Versus Placebo x 28 days In-hospital Fatality (%) Pentoxyfylline Placebo • Predictors of survival • Pentoxyfylline • Age • Creatinine n=49 n = 52 Akriviadis. Gastroenterology. 2000;119:1637-48

  14. STOPAH Trial • Multicenter, double-blind, randomized trial in UK (n=1103) • 2-by-2 factorial design: Prednisolone and/or Pentoxyfylline • Patient selection • Average alcohol consumption > 80 g/d (M) and > 60 g/d (W) • Bilirubin > 4.7 mg/dl, Discriminant function > 32 • Endpoints • Primary: Mortality at 28 days • Secondary: death or LTx at 90 days and at 1 year Thursz. NEJM 2015;372:1619

  15. STOPAH Trial • Primary End Point: 28 day mortality • Multivariable odds ratios: • Prednisolone: 0.61 (p=0.02) • Pentoxyfylline: 1.10 (p=0.62) Prednisolone (p=0.06) Pentoxyfylline (p=0.69) No evidence of benefit for combination

  16. Pentoxyfylline or Not? Akriviadis Trial • Main cause of death = HRS • PTX: 6/12 deaths • Placebo: 22/24 death • Serum creatinine trend STOPAH • HRS: No major concern • Acute kidney injury reported in 2% overall • Terlipressin was allowed according to the site PI discretion. • Serum creatinine at baseline: • 0.88 ± 0.53 cf. creatinine in Akriviadis Trial PTX = 1.2 ± 0.9 Placebo = 1.3 ± 0.8

  17. Treatment Algorithm O’Shea. Hepatology 2010;307

  18. Nutrition Randomized trial of total enteral nutrition (TEN) versus corticosteroids (n=71) • TEN: • 2,000 kcal/d polymeric enteral diet as the sole nutritional supply • Low-sodium, low-fat, water-restricted, enriched in branched-chain amino acids • Continuously infused into the stomach via feeding tube with a peristaltic pump • 8 TEN patients withdrawn from the trial (intolerance in 5) Cabre. Hepatology 2000;32:36-42

  19. Total Enteral Nutrition • No difference in short term mortality (25% versus 31%) • Earlier death with enteral feeding (7 versus 23 days, p=0.03) TEN Prednisolone Mortality during follow-up was higher with steroids: 10/27 vs. 2/24, p=0.04 Cabre. Hepatology 2000;32:36-42

  20. ALD and Overnutrition BMI Survival Asrani(unpublished data)

  21. Medical Management of AH/ALD

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