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 ProgrammeHospitalier de Recherche Clinique; AAH-NAC ClinicalTrials.gov number, NCT00863785.)

 

Supported by ProgrammeHospitalier de Recherche Clinique, a program of the French government that supports hospital-based clinical research.

 

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