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

Background & Aims: Nonalcoholic steatohepatitis (HASH) 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 nor 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 HASH 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, IS 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 amino transferase (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 HASH. Larger trials are warranted.