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: Eric Nguyen-Khac, Thierry Thevenot, Marie-Astrid Piquet, Saïd Benferhat, Odile Goria, Denis Chatelain, Blaise Tramier, François Dewaele, Salah Ghrib, Marika Rudler, Nicolas Carbonell, Hervé Tossou, Abdeslam Bental, Brigitte Bernard-Chabert, Jean-Louis Dupas, AAH-NAC Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 365 Issue 19 Pg. 1781-9 (Nov 10 2011) ISSN: 1533-4406 [Electronic] United States
• PMID: 22070475 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Glucocorticoids
• Prednisolone
• Bilirubin
• Acetylcysteine

Topics

• Acetylcysteine (adverse effects, therapeutic use)
• Antioxidants (adverse effects, therapeutic use)
• Bilirubin (blood)
• Cause of Death
• Drug Therapy, Combination
• Female
• Glucocorticoids (adverse effects, therapeutic use)
• Hepatitis, Alcoholic (drug therapy, mortality)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Prednisolone (adverse effects, therapeutic use)
• Risk Factors