Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis.
OBJECTIVE
Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy. UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective. This study tested their combination.


METHODS
Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were randomly assigned to receive UDCA 12-15 mg.kg-1.day-1 with vitamin E 400 IU twice a day (UDCA/Vit E), UDCA with placebo (UDCA/P), or placebo/placebo (P/P). After 2 years, they underwent a second liver biopsy. Biopsy specimens were collected, blinded, and scored by a single liver pathologist.


RESULTS
Forty eight patients were included, 15 in the UDCA/Vit E group, 18 in the UDCA/P group, and 15 in the P/P group; 8 patients dropped out, none because of side effects. Baseline parameters were not significantly different between the 3 groups. Body mass index remained unchanged during the study. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels diminished significantly in the UDCA/Vit E group. Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group. Histologically, the activity index was unchanged at the end of the study in the P/P and UDCA/P groups, but it was significantly better in the UDCA/Vit E group, mostly as a result of regression of steatosis.


CONCLUSIONS
Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted.
Dufour
Jean-François
JF
Institute of Clinical Pharmacology, University of Bern, Bern, and Department of Gastroenterology, University Hospital of Lausanne, Switzerland. jf.dufour@ikp.unibe.ch
Oneta
Carl M
CM
Gonvers
Jean-Jacques
JJ
Bihl
Florian
F
Cerny
Andreas
A
Cereda
Jean-Michel
JM
Zala
Jean-Franco
JF
Helbling
Beat
B
Steuerwald
Michael
M
Zimmermann
Arthur
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D014815:Vitamins; D014810:Vitamin E; D014580:Ursodeoxycholic Acid; D000637:Transaminases