Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: a randomised, non-inferiority, open trial

J Hepatol. 2014 Oct;61(4):792-8. doi: 10.1016/j.jhep.2014.05.014. Epub 2014 May 15.

Abstract

Background & aims: Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition.

Methods: In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone.

Results: The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups.

Conclusions: The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Keywords: Alcoholic hepatitis; Corticosteroid; Non-inferiority trial; Pentoxifylline.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / adverse effects
  • Drug Monitoring
  • Female
  • Gastrointestinal Hemorrhage / etiology
  • Hepatitis, Alcoholic* / complications
  • Hepatitis, Alcoholic* / drug therapy
  • Hepatitis, Alcoholic* / mortality
  • Hepatitis, Alcoholic* / physiopathology
  • Hepatorenal Syndrome / etiology
  • Humans
  • Infections / etiology
  • Male
  • Middle Aged
  • Patient Selection
  • Pentoxifylline* / administration & dosage
  • Pentoxifylline* / adverse effects
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / adverse effects
  • Prednisolone* / administration & dosage
  • Prednisolone* / adverse effects
  • Severity of Illness Index
  • Survival Rate
  • Therapeutics

Substances

  • Anti-Inflammatory Agents
  • Phosphodiesterase Inhibitors
  • Prednisolone
  • Pentoxifylline