title: Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis.
abstract: BACKGROUND
  Mortality among patients with severe acute alcoholic hepatitis is high, even among those treated with glucocorticoids. We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival.
  
  
  METHODS
  We randomly assigned 174 patients to receive prednisolone plus N-acetylcysteine (85 patients) or only prednisolone (89 patients). All patients received 4 weeks of prednisolone. The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 (at a dose of 150, 50, and 100 mg per kilogram of body weight in 250, 500, and 1000 ml of 5% glucose solution over a period of 30 minutes, 4 hours, and 16 hours, respectively) and on days 2 through 5 (100 mg per kilogram per day in 1000 ml of 5% glucose solution). The prednisolone-only group received an infusion in 1000 ml of 5% glucose solution per day on days 1 through 5. The primary outcome was 6-month survival. Secondary outcomes included survival at 1 and 3 months, hepatitis complications, adverse events related to N-acetylcysteine use, and changes in bilirubin levels on days 7 and 14.
  
  
  RESULTS
  Mortality was not significantly lower in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months (27% vs. 38%, P = 0.07). Mortality was significantly lower at 1 month (8% vs. 24%, P = 0.006) but not at 3 months (22% vs. 34%, P = 0.06). Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months (9% vs. 22%, P = 0.02). In a multivariate analysis, factors associated with 6-month survival were a younger age (P<0.001), a shorter prothrombin time (P<0.001), a lower level of bilirubin at baseline (P<0.001), and a decrease in bilirubin on day 14 (P<0.001). Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group (P = 0.001); other side effects were similar in the two groups.
  
  
  CONCLUSIONS
  Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis, 6-month survival, the primary outcome, was not improved. (Funded by Programme Hospitalier de Recherche Clinique; AAH-NAC ClinicalTrials.gov number, NCT00863785 .).
authors: Service d'Hépato-Gastroentérologie, Amiens University Hospital, and Equipe Région INSERM 24, University of Picardy, Amiens, France. nguyen-khac.eric@chu-amiens.fr
authors: Eric
authors: E
authors: Nguyen-Khac
authors: Thierry
authors: T
authors: Thevenot
authors: Marie-Astrid
authors: MA
authors: Piquet
authors: Saïd
authors: S
authors: Benferhat
authors: Odile
authors: O
authors: Goria
authors: Denis
authors: D
authors: Chatelain
authors: Blaise
authors: B
authors: Tramier
authors: François
authors: F
authors: Dewaele
authors: Salah
authors: S
authors: Ghrib
authors: Marika
authors: M
authors: Rudler
authors: Nicolas
authors: N
authors: Carbonell
authors: Hervé
authors: H
authors: Tossou
authors: Abdeslam
authors: A
authors: Bental
authors: Brigitte
authors: B
authors: Bernard-Chabert
authors: Jean-Louis
authors: JL
authors: Dupas
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D002423:Cause of Death; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006519:Hepatitis, Alcoholic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D000975:Antioxidants; D005938:Glucocorticoids; D011239:Prednisolone; D001663:Bilirubin; D000111:Acetylcysteine