Adding N-Acetylcysteine to Glucocorticoids May Improve Outcomes in Patients with Severe Alcoholic Hepatitis

This randomized controlled trial conducted in 11 French university hospitals sought to determine whether N-acetylcysteine [NAC], an antioxidant used to treat acetaminophen-induced hepatitis, further reduced mortality in patients treated with prednisolone for severe alcoholic hepatitis. Subjects (N=174) were age 18 or older; had consumed, on average, >50 g alcohol per day in the past 3 months; had a Maddrey’s discriminant function* of 32 or more; and had liver histologic findings consistent with alcoholic hepatitis. The long list of exclusion criteria included other possible causes of liver disease (e.g., hepatitis B or C), HIV infection, and “serious cardiac, respiratory or neurologic disease.” All patients received oral prednisolone for 28 days, while 85 also received intravenous NAC on days 1–5.

• Mortality rates and hazard ratios (HR) for patients in the prednisolone-only (PRED) and prednisolone plus NAC (PRED-NAC) arms were as follows:

†As reported in the paper.

• Adverse events were no higher in the PRED-NAC arm, and 2 major adverse events (hepatorenal syndrome and infection) were significantly lower.

Comments:

Although this study failed to show significantly reduced mortality at 6 months (the primary endpoint), a significant short-term benefit was seen in the PRED-NAC arm with no serious adverse events. The failure may simply have been due to lack of sufficient power. It is also possible that longer term outcomes would be better with longer courses of NAC treatment.

Darius A. Rastegar, MD

Reference:

Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus Nacetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365(19):1781–1789.