title: Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: a randomized clinical trial.
abstract: OBJECTIVE
  Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown.
  
  
  OBJECTIVE
  To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.
  
  
  METHODS
  Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome.
  
  
  METHODS
  Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days.
  
  
  METHODS
  Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment.
  
  
  RESULTS
  In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07).
  
  
  CONCLUSIONS
  In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01214226.
authors.affiliation: Service des Maladies de l'Appareil digestif, Hôpital Huriez, Lille, France. philippe.mathurin@chru-lille.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Louvet
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Pierre
authors.initials: P
authors.lastname: Nahon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carbonell
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boursier
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Anty
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Diaz
authors.forename: Dominique
authors.initials: D
authors.lastname: Thabut
authors.forename: Romain
authors.initials: R
authors.lastname: Moirand
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.forename: Nathalie
authors.initials: N
authors.lastname: Talbodec
authors.forename: Thierry
authors.initials: T
authors.lastname: Paupard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Naveau
authors.forename: Christine
authors.initials: C
authors.lastname: Silvain
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Sobesky
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva-Delcambre
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Julia
authors.initials: J
authors.lastname: Salleron
authors.forename: Thong
authors.initials: T
authors.lastname: Dao
mesh_terms: D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage*; D006519:Hepatitis, Alcoholic / Q000188:drug therapy*; D006530:Hepatorenal Syndrome; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage*; D011239:Prednisolone / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D016166:Free Radical Scavengers; D005938:Glucocorticoids; D011239:Prednisolone; D010431:Pentoxifylline