Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data
- Philippe Mathurin1,
- John O'Grady2,
- Robert L Carithers3,
- Martin Phillips2,
- Alexandre Louvet1,
- Charles L Mendenhall4,
- Marie-José Ramond5,
- Sylvie Naveau6,
- Willis C Maddrey7,
- Timothy R Morgan8
- 1Service des Maladies de l'Appareil digestif, Universite Lille Nord de France, UDSL and INSERM, Lille, France
- 2Institute of Liver Studies, King's College Hospital, London, UK
- 3Department of Medicine, Seattle, Washington, USA
- 4Veterans Affairs Medical Center, Cincinnati, Ohio, USA
- 5Hôpital Beaujon, Clichy, France
- 6Service d'Hépato-Gastroentérologie, Hôpital Antoine-Béclère, Clamart, France
- 7Department of Medicine, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
- 8Gastroenterology Section, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USA
- Correspondence to Philippe Mathurin, Service des Maladies de l'Appareil digestif, Hôpital Huriez, Rue Polonovski, F-59037 Lille, France;
- Received 24 July 2010
- Accepted 1 September 2010
- Published Online First 12 October 2010
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.
Funding The cost of this study was borne by the authors' institutions.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.