Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone

Summary

35% of Acute Alcoholic Hepatitis patients (AAH) do not respond to corticoids and died after 6 months. Chronic alcohol abuse depletes glutathione in the hepatocytes and makes the latter more sensitive to excessive TNFα levels. Re-establishment of a stock of antioxidants by administration of a precursor (N-acetyl cysteine, NAC) in combination with corticoids (C) could make the hepatocytes more resistant and improve survival. The investigators' study's primary endpoint was improvement of survival at 6 months. The secondary endpoints were survival at 1 and 3 months, tolerance of NAC and a drop in blood bilirubin levels at D7

Timeline

Start

2004-04

Primary completion

2009-08

Completion

2009-09

Outcome

Missed primary endpoint

paper 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). PMID 22070475 ↗

paper 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. PMID 22070475 ↗

Publications

• Nguyen-Khac E, Thevenot T, Piquet MA, Benferhat S, Goria O, Chatelain D, Tramier B, Dewaele F, Ghrib S, Rudler M, Carbonell N, Tossou H, Bental A, Bernard-Chabert B, Dupas JL; AAH-NAC Study Group. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011 Nov 10;365(19):1781-9. doi: 10.1056/NEJMoa1101214.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	N-acetylcysteine	Small molecule	100 mg/kg	Intravenous
Background	Prednisolone	Other / unclassified	40 mg	—

Indications