title: Prednisolone or pentoxifylline for alcoholic hepatitis.
abstract: BACKGROUND
  Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists.
  
  
  METHODS
  We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline.
  
  
  RESULTS
  A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002).
  
  
  CONCLUSIONS
  Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).
authors.affiliation: From Imperial College (M.R.T., N.V.), King's College Hospital (J.O.), and the Royal Free Hospital (D.P.), London, Royal Liverpool Hospital (P. Richardson) and Aintree Hospital (S.H.), Liverpool, Addenbrookes Hospital, Cambridge (M.A.), Derby Royal Hospital, Derby (A.A.), Southampton Clinical Trials Unit, University of Southampton (M.B., N.D., J.M., I.R., P. Roderick, L.S.), and University Hospital Southampton NHS Foundation Trust (M.W.), Southampton, Faculty of Medical Sciences, Newcastle University (C.P.D.), and Newcastle upon Tyne Hospitals NHS Foundation Trust (S.M.), Newcastle upon Tyne, Sheffield Teaching Hospitals Foundation Trust, Sheffield (D.G.), Edinburgh Royal Infirmary, Edinburgh (A. MacGilchrist), Leicester Royal Infirmary, Leicester (A.G.), Bristol Royal Infirmary, Bristol (A. McCune), Nottingham University Hospitals NHS Trust and National Institute for Health Research Biomedical Research Unit, Queens Medical Centre, Nottingham (S.R.), and the Glasgow Royal Infirmary, Glasgow (E.H.F.) - all in the United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Thursz
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Michael
authors.initials: M
authors.lastname: Allison
authors.forename: Andrew
authors.initials: A
authors.lastname: Austin
authors.forename: Megan
authors.initials: M
authors.lastname: Bowers
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.forename: Nichola
authors.initials: N
authors.lastname: Downs
authors.forename: Dermot
authors.initials: D
authors.lastname: Gleeson
authors.forename: Alastair
authors.initials: A
authors.lastname: MacGilchrist
authors.forename: Allister
authors.initials: A
authors.lastname: Grant
authors.forename: Steven
authors.initials: S
authors.lastname: Hood
authors.forename: Steven
authors.initials: S
authors.lastname: Masson
authors.forename: Anne
authors.initials: A
authors.lastname: McCune
authors.forename: Jane
authors.initials: J
authors.lastname: Mellor
authors.forename: John
authors.initials: J
authors.lastname: O'Grady
authors.forename: David
authors.initials: D
authors.lastname: Patch
authors.forename: Ian
authors.initials: I
authors.lastname: Ratcliffe
authors.forename: Paul
authors.initials: P
authors.lastname: Roderick
authors.forename: Louise
authors.initials: L
authors.lastname: Stanton
authors.forename: Nikhil
authors.initials: N
authors.lastname: Vergis
authors.forename: Mark
authors.initials: M
authors.lastname: Wright
authors.forename: Stephen
authors.initials: S
authors.lastname: Ryder
authors.forename: Ewan H
authors.initials: EH
authors.lastname: Forrest
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007239:Infections / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011239:Prednisolone; D010431:Pentoxifylline