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.
Asma Siddique, Kris V. Kowdley. Adding N-acetylcysteine to prednisolone reduced early mortality in severe alcoholic hepatitis. Ann Intern Med. 2012;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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