Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis

Clin Gastroenterol Hepatol. 2006 Dec;4(12):1537-43. doi: 10.1016/j.cgh.2006.09.025.

Abstract

Background & aims: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Cholagogues and Choleretics / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transaminases / blood
  • Treatment Outcome
  • Ursodeoxycholic Acid / therapeutic use*
  • Vitamin E / therapeutic use*
  • Vitamins / therapeutic use*

Substances

  • Cholagogues and Choleretics
  • Vitamins
  • Vitamin E
  • Ursodeoxycholic Acid
  • Transaminases