A randomized trial of antioxidant therapy alone or with corticosteroids in acute alcoholic hepatitis.
OBJECTIVE
Oxidative stress is putatively involved in the pathogenesis of alcohol-induced liver injury. This trial was devised to determine whether antioxidant therapy, alone or as an adjunct to corticosteroids, improved survival in patients with acute alcoholic hepatitis.


METHODS
Patients with a severe alcoholic hepatitis were stratified by sex and steroid use, and then randomized. The active group received N-acetylcysteine for one week, and vitamins A-E, biotin, selenium, zinc, manganese, copper, magnesium, folic acid and Coenzyme Q daily for 6 months. The trial was double blinded and placebo controlled. The primary end-point was mortality within 6 months.


RESULTS
Thirty-six (20 male, 16 female; mean discriminant function (DF) 86.6) received active drug, and 34 (18 male, 16 female; mean DF 76.4) received placebo. 180-day survival was not significantly different between patients receiving drug and placebo (52.8% vs. 55.8%, p=0.699). This was not affected by stratification for steroid use or sex. The only predictors of survival in multivariate analysis were initial bilirubin (p=0.017), white cell count (p=0.016) and age (p=0.037). Treatment allocation did not affect survival in multivariate analysis (p=0.830).


CONCLUSIONS
Antioxidant therapy, alone or in combination with corticosteroids, does not improve 6-month survival in severe alcoholic hepatitis.
Stewart
Stephen
S
Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Prince
Martin
M
Bassendine
Margaret
M
Hudson
Mark
M
James
Oliver
O
Jones
David
D
Record
Chris
C
Day
Christopher P
CP
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000975:Antioxidants / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D016019:Survival Analysis; D017211:Treatment Failure
D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D001663:Bilirubin