Background. In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis. Methods. We conducted a two‐year, multicenter, double‐blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy‐proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 μmol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction. Results. Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P < 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P < 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ‐glutamyltransferase, cholesterol, and IgM (all P < 0.001); the antimitochondrial‐antibody titer (P < 0.01); and the Mayo risk score (P < 0.001). Follow‐up analysis of 95 liver‐biopsy specimens showed a significant improvement in the mean histologic score (P < 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol. Conclusions. Ursodiol is a safe and effective treatment for primary biliary cirrhosis.
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