Although glucocorticoid treatment is recommended for the treatment of severe acute alcoholic hepatitis and improves survival, mortality remains high, with 35% of patients dying within 6 months. Long-term alcohol consumption is associated with the production of proinflammatory cytokines. Combination therapy with an antioxidant and glucocorticoids, by acting on the inflammatory process and reconstituting cellular glutathione reserves, has been proposed as a treatment option.  It has been suggested that N-acetylcysteine could have value as an antioxidant in the treatment of acute alcoholic hepatitis, because the thiol group in N-acetylcysteine is able to reduce levels of free radicals. Researchers therefore conducted this study to evaluate the efficacy of glucocorticoids plus N-acetylcysteine, as compared with glucocorticoids alone, in patients with severe acute alcoholic hepatitis.

The study involved 174 patients randomised to prednisolone plus N-acetylcysteine (n=85) or only prednisolone (n=89). All patients received 4 weeks of prednisolone. The prednisolone–N-acetylcysteine group received IV N-acetylcysteine on day 1 (150, 50, and 100mg/kg in 250, 500, and 1000ml of 5% glucose over 30 minutes, 4 hours, and 16 hours, respectively) and on days 2 through 5 (100mg/kg per day in 1000 ml of 5% glucose). The prednisolone-only group received an infusion of 1000ml 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.

The following findings were reported:

• 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).

• 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.

The researchers conclude that in patients with severe acute alcoholic hepatitis, the combination of N-acetylcysteine and prednisolone did not significantly improve 6-month survival, as compared with prednisolone only.