SFGH morning report pearls 11.2: acute alcoholic hepatitis

Acute alcoholic hepatitis:

    • characteristic features: jaundice, anorexia, fever, tender hepatomegaly, moderate elevation in transaminases in a patient with a history of prolonged and heavy alcohol use (often >100 g/day for >20 years) and exclusion of other causes of liver disease
  • Maddrey’s discriminant function: 4.6 * (patient’s PT in seconds – control PT in seconds) + patient serum bili; value 32 or higher indicates severe alc hep and mortality of 20-30% at one month
  • What about the evidence?
    • GI bleed, evidence of infection, pancreatitis, usually exclusion criteria for prednisolone trials
    • lots of controversy!  a few of the relevant studies:
  • Cochrane meta-analysis of 15 randomized trials comparing steroids to placebo:
    • trend toward benefit with glucocorticoids, not statistically significant
  • Rambaldi et al re-meta-analysis of the 5 largest studies from the Cochrane review
    • significant reduction in 28-day mortality with DF of 32 or higher with glucocorticoids
  • One of four randomized controlled trials showed a signficant benefit of pentoxifylline compared to placebo
  • 7/15 NEJM Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH trial):
    • randomized, double-blind trial with 2×2 factorial design to look at treatment with prednisolone or pentoxifylline
    • studied 1103 patients; excluded those with chronic liver disease
    • pentoxifylline did not improve survival for patients with alc hep
    • prednisolone was associated with a reduction in 28-day mortality that approached statistical significance (p = 0.06); no difference at 90 days and 1 year
    • some critique that the diagnosis of alc hep not confirmed by biopsy
  • If there is no improvement in the DF after 1 week of therapy, ongoing treatment is not recommended and thought to have little benefit
  • Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000;119:1637-1648
  • Mathurin P, O’Grady J, Carithers RL, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 2011; 60:255.
  • Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372:1619.
  • Rambaldi A, Saconato HH, Christensen E, et al. Systematic review: glucocorticosteroids for alcoholic hepatitis–a Cochrane Hepato-Biliary Group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Aliment Pharmacol Ther 2008; 27:1167.

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