alcoholic hepatitis
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Epidemiology
women at greater risk than men
Pathology
- alcohol induces hepatic microsomal enzymes
- enhanced risk of acetaminophen-induced hepatitis
- centrilobular hepatocellular necrosis
- pericentric hyalin
- polymorphonuclear infiltration
- micro & macrovesicular fatty change of hepatocytes
- 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
- fatty liver with inflammation is alcoholic steatohepatitis
Clinical manifestations
Laboratory
- abnormal liver function tests
- modest increase in serum AST (150-250 U/L); 300-500 U/L[1]
- serum AST is generally > 2x serum ALT
- a much greater increase in serum AST (3000-48,000 U/L) is observed with alcohol-associated acetaminophen hepatitis
- serum gamma-glutamyltransferase (GGT) is elevated
- complete blood count
- leukocytosis
- MCV may be elevated
- liver function tests
- prothrombin time may be increased
- serum bilirubin > 3 mg/dL
- Maddrey discriminant factor may be useful for determining benefit of glucocorticoids
- 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
Management
- abstinence from alcohol[1]
- prednisolone 40 mg/day for 28 days
- patients with coexisting hepatic encephalopathy[3] & ascites[1]
- guidelines restrict use of glucocorticoids to those with Maddrey discriminant factor > 32[4], MELD >= 18[1], or GAHS >= 9 or encephalopathy[1]
- if serum bilirubin does not improve or Lille score > 0.45 on day 7, discontinue glucocorticoids[1][14]
- avoid corticosteroids with GI bleed, infection, pancreatitis, or renal insufficiency[1]
- non-significant improvement in 28 day mortality (14% vs 17% for placebo)[9]
- does not improve 90 day survival[9]
- 90-day mortality rate among glucocorticoid-treated patients is 36%[10]
- no benefit of glucocorticoids (Cochrane Review)[13]
- N-acetylcysteine administration if acetaminophen hepatitis is suspected, not useful otherwise[6]
- 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]
- not useful as adjunct to prednisolone[7]
- S-adenosylmethionine (SAM) is an experimental therapy
- prognosis:
- MELD score better than Child-Pugh classification or Maddrey discriminant function[5]
- MELD score >= 18
- Maddrey discriminant function >= 32
- Glascow alcoholic hepatitis score (GAHS) >=9[1]
- liver transplantation
- traditionally requires 6 months of abstinence
- early liver transplantation may improve survival [6.15]
- baclofen effective in preventing alcohol relapse in patients with alcoholic liver disease
More general terms
Additional terms
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 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 - ↑ 2.0 2.1 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: https://www.ncbi.nlm.nih.gov/pubmed/11113085
- ↑ 3.0 3.1 Ramond MJ et al, A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med 1992, 326:507 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1531090
- ↑ 4.0 4.1 Kulkarni K et al, The role of discriminant factor in the assessment and treatment of alcoholic hepatitis. J Clin Gastroenterol 2004, 38:453 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15100527
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/15826720
- ↑ 6.0 6.1 Nguyen-Khac E et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med 2011 Nov 10; 365:1781. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22070475
Mathurin P et al Early liver transplantation for severe alcoholic hepatitis. N Engl J Med 2011Nov 10; 365:1790 PMID: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/22070481 - ↑ 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24026598 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1737041
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20034030
- ↑ 9.0 9.1 9.2 9.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25901427 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1412278
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/27922027
- ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/28602070
- ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/27636406
- ↑ 13.0 13.1 Pavlov CS, Varganova DL, Casazza G et al. Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev 2017 Nov 2; 11:CD001511 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29096421
- ↑ 14.0 14.1 Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG clinical guideline: Alcoholic liver disease. Am J Gastroenterol 2018 Jan 16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29336434
- ↑ Lee BP, Mehta N, Platt L et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology 2018 Apr 12; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29655837
- ↑ 16.0 16.1 16.2 NEJM Knowledge+ Gastroenterology