Asma Siddique, MD; Kris V. Kowdley, MD, FACP
Does adding N-acetylcysteine (NAC) to prednisolone reduce mortality in patients with severe acute alcoholic hepatitis?
Randomized controlled trial. ClinicalTrials.gov NCT00863785.
11 university hospitals in France.
180 patients ≥ 18 years of age (mean age 52 y, 60% men) who were hospitalized for severe acute alcoholic hepatitis and had a mean alcohol intake > 50 g/d in the previous 3 months, Madrey discriminant function score ≥ 32, and histologic confirmation of alcoholic hepatitis. Exclusion criteria were the hepatorenal syndrome; hepatocellular carcinoma; uncontrolled bacterial infection or gastrointestinal hemorrhage in the past 4 days; infection with hepatitis B or C virus; HIV infection; autoimmune hepatitis; hemochromatosis; Wilson disease; α1-antitrypsin deficiency; acetaminophen-induced hepatitis; cancer; NAC allergy; and serious cardiac, respiratory, or neurologic disease.
Oral prednisolone, 40 mg/d, plus NAC (n = 85), or prednisolone only (n = 89). All patients received prednisolone for 28 days. On day 1, the NAC group received IV NAC, 150 mg/kg body weight, in 250 mL of 5% glucose solution over 30 minutes, 50 mg/kg in 500 mL of 5% glucose over 4 hours, and 100 mg/kg in 1000 mL of 5% glucose over 16 hours; on days 2 to 5, they received 100 mg/kg/d in 1000 mL of 5% glucose. On days 1 to 5, the prednisolone-only group received 1000 mL/d of 5% IV glucose solution.
Primary outcome was mortality at 6 months. Secondary outcomes included mortality at 1 month and adverse events related to NAC use. 174 patients were required to detect a 20% improvement in survival at 6 months with 90% power (α = 0.05) and an assumed survival rate of 67% in the prednisolone-only group.
97% at 6 months (modified intention-to-treat).
Prednisolone plus NAC reduced risk for death at 1 month but not at 6 months compared with prednisolone only (Table). Patients in the prednisolone plus NAC group had lower risk for the hepatorenal syndrome and infection (Table).
Adding N-acetylcysteine to prednisolone reduced risk for mortality at 1 month but not 6 months in patients with severe acute alcoholic hepatitis.
Prednisolone (pred) plus N-acetylcysteine (NAC) vs pred only in patients with severe acute alcoholic hepatitis†
†NS = not significant; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates, hazard ratios (mortality), and odds ratios (hepatorenal syndrome, infection) in article.
Siddique A, Kowdley KV. Adding N-acetylcysteine to prednisolone reduced early mortality in severe alcoholic hepatitis. Ann Intern Med. ;156:JC5–5. doi: 10.7326/0003-4819-156-10-201205150-02005
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Published: Ann Intern Med. 2012;156(10):JC5-5.
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