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alcoholic hepatitis

Epidemiology: women at greater risk than men Pathology: 1) alcohol induces hepatic microsomal enzymes 2) enhanced risk of acetaminophen-induced hepatitis 3) centrilobular hepatocellular necrosis 4) pericentric hyalin 5) polymorphonuclear infiltration 6) micro & macrovesicular fatty change of hepatocytes 7) alcoholic binging may cause fatty liver - fatty liver with inflammation is alcoholic steatohepatitis - mild steatohepatitis is common, generally asymptomatic - severe steatohepatitis is symptomatic alcoholic hepatitis Clinical manifestations: 1) abdominal tenderness 2) hepatomegaly 3) jaundice 4) fever 5) ascites due to portal hypertension 6) encephalopathy Laboratory: 1) abnormal liver function tests a) modest increase in serum AST (150-250 U/L); 300-500 U/L [1] b) serum AST is generally > 2x serum ALT c) a much greater increase in serum AST (3000-48,000 U/L) is observed with alcohol-associated acetaminophen hepatitis d) serum gamma-glutamyltransferase (GGT) is elevated 2) complete blood count - leukocytosis - MCV may be elevated 3) liver function tests a) prothrombin time may be increased b) serum bilirubin > 3 mg/dL c) Maddrey discriminant factor may be useful for determining benefit of glucocorticoids 4) serum ferritin for hemochromatosis not appropriate in setting of acute inflammation [16] Radiology: - RUQ ultrasound - liver elastography (Fibroscan) not appropriate in setting of acute inflammation (may overestimate degree of fibrosis) [16] Complications: - hepatorenal syndrome - fulminant liver failure - death Management: 1) abstinence from alcohol [1] 2) prednisolone 40 mg/day for 28 days a) patients with coexisting hepatic encephalopathy [3] & ascites [1] b) guidelines restrict use of glucocorticoids to those with Maddrey discriminant factor > 32 [4], MELD >= 18 [1], or GAHS >= 9 or encephalopathy [1] c) if serum bilirubin does not improve or Lille score > 0.45 on day 7, discontinue glucocorticoids [1,14] d) avoid corticosteroids with GI bleed, infection, pancreatitis, or renal insufficiency [1] e) non-significant improvement in 28 day mortality (14% vs 17% for placebo) [9] f) does not improve 90 day survival [9] g) 90-day mortality rate among glucocorticoid-treated patients is 36% [10] h) no benefit of glucocorticoids (Cochrane Review) [13] 3) N-acetylcysteine administration if acetaminophen hepatitis is suspected, not useful otherwise [6] 4) pentoxifylline 400 mg TID [2] no longer recommemded [1] (MKSAP19) - not useful as adjunct to prednisolone [7] - combination of prednisolone + pentoxifylline may reduce incidence of hepatorenal syndrome [12] - no better than placebo [9] - preferred vs glucocorticoid with hepatorenal syndrome [11] 5) S-adenosylmethionine (SAM) is an experimental therapy 6) prognosis: a) MELD score better than Child-Pugh classification or Maddrey discriminant function [5] b) MELD score >= 18 c) Maddrey discriminant function >= 32 c) Glascow alcoholic hepatitis score (GAHS) >=9 [1] 7) liver transplantation a) traditionally requires 6 months of abstinence b) early liver transplantation may improve survival [6.15] 8) baclofen effective in preventing alcohol relapse in patients with alcoholic liver disease

Interactions

disease interactions

Related

acetaminophen poisoning alcoholism (includes binge drinking) Mallory body; alcoholic hyalin

General

alcoholic liver disease (ALD) hepatitis

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2012, 2018,2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  2. Journal Watch 21(3):21, 2001 Akriviadis et al, Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000, 119:1637 PMID: 11113085
  3. Ramond MJ et al, A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992, 326:507 PMID: 1531090
  4. Kulkarni K et al, The role of discriminant factor in the assessment and treatment of alcoholic hepatitis. J Clin Gastroenterol 2004, 38:453 PMID: 15100527
  5. Srikureja W et al, MELD score is a better prognostic model than Child-Turcotte- Pugh score of Discriminant Function score in patients with alcoholic hepatitis. J Hepatol 2005, 42:700 PMID: 15826720
  6. Nguyen-Khac E et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med 2011 Nov 10; 365:1781. PMID: 22070475 - Mathurin P et al Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011Nov 10; 365:1790 PMID: 22070476 - Brown RS Jr. Transplantation for alcoholic hepatitis - Time to rethink the 6-month "rule." N Engl J Med 2011 Nov 10; 365:1836. PMID: 22070481
  7. Mathurin P et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. JAMA 2013; 310:1033 PMID: 24026598 http://jama.jamanetwork.com/article.aspx?articleid=1737041
  8. O'Shea RS, Dasarathy S, McCullough AJ; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010 Jan;51(1):307-28 PMID: 20034030
  9. Thursz MR, Richardson P, Allison M et al Prednisolone or Pentoxifylline for Alcoholic Hepatitis. N Engl J Med 2015; 372:1619-1628. April 23, 2015 PMID: 25901427 http://www.nejm.org/doi/full/10.1056/NEJMoa1412278
  10. Garcia-Saenz-de-Sicilia M et al. A day-4 Lille Model predicts response to corticosteroids and mortality in severe alcoholic hepatitis. Am J Gastroenterol 2016 Dec 6 PMID: 27922027
  11. Rana R, Wang SL, Li J, Xia L, Song MY, Yang CQ. A prognostic evaluation and management of alcoholic hepatitis. Minerva Med. 2017 Jun 9. PMID: 28602070
  12. Lee YS, Kim HJ, Kim JH et al Treatment of Severe Alcoholic Hepatitis With Corticosteroid, Pentoxifylline, or Dual Therapy: A Systematic Review and Meta- Analysis. J Clin Gastroenterol. 2017 Apr;51(4):364-377. PMID: 27636406
  13. Pavlov CS, Varganova DL, Casazza G et al. Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev 2017 Nov 2; 11:CD001511 PMID: 29096421
  14. Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG clinical guideline: Alcoholic liver disease. Am J Gastroenterol 2018 Jan 16 PMID: 29336434
  15. Lee BP, Mehta N, Platt L et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology 2018 Apr 12; PMID: 29655837
  16. NEJM Knowledge+ Gastroenterology