title: A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis.
abstract: Tumor necrosis factor-alpha (TNF-alpha) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score >/=32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% +/- 11%) than in group B (18% +/- 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P <.002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections.
authors.affiliation: Services d'Hépato-Gastroentérologie, Hôpital Antoine Béclère, Clamart, Assistance Publique-Hôpitaux de Paris, France. sylvie.naveau@abc.ap-hop-paris.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Naveau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.forename: Pauline
authors.initials: P
authors.lastname: Jouet
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Piquet
authors.forename: Thierry
authors.initials: T
authors.lastname: Davion
authors.forename: Frédéric
authors.initials: F
authors.lastname: Oberti
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
mesh_terms: D000208:Acute Disease; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D011239:Prednisolone; D000069285:Infliximab