Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data.
Gastroenterology. 2018 May 05;:
Authors: Louvet A, Thursz MR, Kim DJ, Labreuche J, Atkinson S, Sidhu SS, O'Grady JG, Akriviadis E, Sinakos E, Carithers RL, Ramond MJ, Maddrey WC, Morgan TR, Duhamel A, Mathurin P
BACKGROUND & AIMS: We performed a meta-analysis of individual patient data from 11 randomized controlled trials comparing corticosteroids, pentoxifylline, or their combination in patients with severe alcoholic hepatitis. We compared the effects of the treatments on survival for 28 days or 6 months, and response to treatment based on the Lille model.
METHODS: We searched PubMed for randomized controlled trials of pharmacologic therapy for severe alcoholic hepatitis. Our final analysis comprised 11 studies, of 2111 patients. We performed four meta-analyses of the effects of corticosteroids vs. placebo or control, corticosteroids vs. pentoxifylline, corticosteroids and pentoxifylline vs. corticosteroids and placebo or control, and pentoxifylline vs. placebo. In each meta-analysis, the effect of treatment on the primary outcome (overall survival at 28 days, defined as the period from the first day of assigned treatment to 28 days) was estimated using a Cox proportional hazards regression model, stratified by trial.
RESULTS: Corticosteroid treatment significantly decreased risk of death within 28 days compared to controls (hazard ratio [HR], 0.64; 95% CI, 0.48-0.86) or to pentoxifylline (HR, 0.64; 95% CI, 0.43-0.95). In multiple imputation and complete case analyses, the effect of corticosteroids compared to controls remained significant. When we compared corticosteroids vs. pentoxifylline, the corticosteroid effect remained significant in the complete case analysis (HR, 0.66; P=.04) but not in multiple-imputation analysis (HR, 0.71; P=.08). There was no difference in 28-day mortality when patients were given a combination of corticosteroids and pentoxifylline vs. corticosteroids alone or between patients given pentoxifylline vs. control. In our analysis of secondary outcomes, we found no significant differences in 6-month mortality when any treatments or controls were compared. Corticosteroids were significantly associated with increased response to therapy compared with controls (relative risk, 1.24; 95% CI, 1.10-1.41) or pentoxifylline (relative risk, 1.43; 95% CI, 1.20-1.68). We found no difference in response to therapy between patients given a combination of corticosteroids and pentoxifylline vs. corticosteroids alone or pentoxifylline vs. controls.
CONCLUSIONS: In a meta-analysis of 4 controlled trials, we found corticosteroid use to reduce risk of death within 28 days of treatment, but not in the following 6 months. This loss of efficacy over time indicates a need for new therapeutic strategies to improve medium-term outcomes.
PMID: 29738698 [PubMed - as supplied by publisher]