Prednisolone, Pentoxifylline, and Survival of Patients with Severe Alcoholic Hepatitis
Clinical question: Does the addition of pentoxifylline to prednisolone improve six-month mortality compared to prednisolone alone in patients with severe alcoholic hepatitis?
Background: Prednisolone improves liver function and reduces inflammation in patients with alcoholic hepatitis. Pentoxifylline appears to have a protective effect against hepatorenal syndrome in patients with severe alcoholic hepatitis. The medications have different mechanisms of action; therefore, the researchers hypothesized that the combination of medication would improve outcomes.
Study design: Multi-center, randomized, double-blinded clinical trial.
Setting: One Belgian and 23 French hospitals, from December 2007 to October 2010.
Synopsis: This study randomized 270 patients to receive either prednisolone and pentoxifylline or prednisolone and placebo for 28 days. Acute alcoholic hepatitis was defined by a positive biopsy, onset of jaundice three months prior to the study, and a Maddrey’s discriminant function score of >32. All patients were assessed for response to treatment using the Lille model at seven days of treatment, occurrence of hepatorenal syndrome, and survival at six months.
Results showed no significant difference in treatment response, alcohol relapse, death, time to death, or occurrence of hepatorenal syndrome between the two treatment groups; however, there were fewer episodes of hepatorenal syndrome in the pentoxifylline group.
Patients considered responders by the Lille model and those with lower Model for End-Stage Liver Disease scores had improved mortality. Patients treated with pentoxifylline had lower rates of hepatorenal syndrome at one month but no difference by six months. Patients with a lower Lille score had significantly less incidence of hepatorenal syndrome. The study may be underpowered to accurately determine outcomes other than six-month survival.
Bottom line: Adding pentoxifylline to prednisolone does not improve six-month survival in severe alcoholic hepatitis compared to prednisolone alone.
Citation: Mathurin P, Louvet A, Duhamel A, et al. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial. 2013;310(10):1033-1041.
