Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: Meta-analysis of individual patient data

Philippe Mathurin, John O'Grady, Robert L. Carithers, Martin Phillips, Alexandre Louvet, Charles L. Mendenhall, Marie José Ramond, Sylvie Naveau, Willis C. Maddrey, Timothy R. Morgan

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

Abstract

Introduction: A meta-analysis was performed using individual patient data from the five most recent randomised controlled trials (RCTs) which evaluated corticosteroids in severe alcoholic hepatitis (Maddrey discriminant function (DF) ≥32 or encephalopathy). This approach overcomes limitations associated with the use of literature data and improves the relevance of the study and estimates of effect size. Aims: To compare 28-day survival between corticosteroid- and non-corticosteroid-treated patients and to analyse the response to treatment using the Lille model. Methods: Individual patient data were obtained from five RCTs comparing corticosteroid treatment with placebo (n=3), enteral nutrition (n=1) or an antioxidant cocktail (n=1). Results: 221 patients allocated to corticosteroid treatment and 197 allocated to non-corticosteroid treatment were analysed. The two groups were similar at baseline. 28-day survival was higher in corticosteroid-treated patients than in non-corticosteroid-treated patients (79.97±2.8% vs 65.7±3.4%, p=0.0005). In multivariate analysis, corticosteroids (p=0.005), DF (p=0.006), leucocytes (p=0.004), Lille score (p<0.00001) and encephalopathy (p=0.003) were independently predictive of 28-day survival. A subgroup analysis was performed according to the percentile distribution of the Lille score. Patients were classified as complete responders (Lille score ≤0.16; ≤35th percentile), partial responders (Lille score 0.16-0.56; 35th-70th percentile) and null responders (Lille ≥0.56; ≥70th percentile). 28-day survival was strongly associated with these groupings (91.1±2.7% vs 79.4±3.8% vs 53.3±5.1%, p<0.0001). Corticosteroids had a significant effect on 28-day survival in complete responders (HR 0.18, p=0.006) and in partial responders (HR 0.38, p=0.04) but not in null responders. Conclusion: Analysis of individual data from five RCTs showed that corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis. The survival benefit is mainly observed in patients classified as responders by the Lille model.

Original languageEnglish (US)
Pages (from-to)255-260
Number of pages6
JournalGut
Volume60
Issue number2
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Gastroenterology

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