Treatment of Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone (HAA-NAC)

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

Treatment of Acute Severe Alcoholic Hepatitis With Corticoids Plus N Acetyl Cysteine Versus Corticoids Alone: a French Multicentre Randomized Controlled Study.

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

AAH patients (Maddrey score > 32 and compatible histological results) should centrally randomized into the C-NAC or C groups. Both groups received 4 weeks of prednisolone treatment, plus NAC for the combination therapy group (D1: 150, 50 and 100 mg/kg in 250, 500 and 1000 mL of 5% glucose-saline (G5%) respectively, at t=30 minutes, 4 and 16 hours; D2 to D5, 100 mg/kg in 1000 mL of G5%). Group C received 1000 mL of G5%, D1-5

40 mg/d prednisolone N Acetyl Cysteine infusion 150mg/kg in 30 minutes then 50 mg/kg in 4 h then 100mg/kg in 16 h and finally 100mg/d2 to d5

40 mg/d prednisolone N Acetyl Cysteine infusion 150mg/kg in 30 minutes then 50 mg/kg in 4 h then 100mg/kg in 16 h and finally 100mg/d2 to d5

Inclusion Criteria: Patient consent Chronic alcohol intake in the last 3 to 6 months Maddrey score ≥ 32 Liver histology compatible Exclusion Criteria: Hepato renal syndrome Hepatocarcinoma Recent variceal haemorrhage Recent bacterial infections Other liver diseases associated (HCV, HBV, hemochromatosis, AIH) Cancers or cardiac and respiratory, HIV infection NAC Allergy No patient consent Acetaminophen intoxication

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.