Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial

Background/Aim: The aim of this study was to assess the efficacy of ursodeoxycholic acid (UDCA) for primary biliary cirrhosis in a randomized, double-blind placebo-controlled trial. Methods: Consecutive patients (n=192) were randomized to receive 14–16 mg UDCA/kg/day or placebo. Patients underwent a complete history, physical examination, liver chemistries, immunological determinations and liver biopsy at entry and at the end of the trial, which lasted for at least 2 years. Patients were seen every 3 months and the median follow-up was 3.4 years (range 0.3 to 6.1 years). Results: Patients receiving UDCA (99) or placebo (93) were comparable with regard to age, sex, biochemical parameters and liver histology. UDCA treatment was associated with decreases in alkaline phosphatase, gammaglutamyl transferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during the follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo) discontinued the trial because of noncompliance (n=11), voluntary withdrawal (n=19) or adverse effects (n=1). Treatment failure (death or liver transplantation) was observed in 17 patients receiving UDCA and in 11 patients receiving placebo. Times to death or liver transplantation and to clinical complications were not significantly different in patients receiving UDCA or placebo. Histological analysis indicates that UDCA improved portal inflammation and prevented histological stage progression. By contrast, histological stage as well as ductular proliferation and ductopenia progressed in patients receiving placebo. Conclusions: Although UDCA treatment did not significantly affect time to death or liver transplantation and to clinical complications, the effects on both cholestasis and liver histology suggest that UDCA is safe and may be useful for preventing the progression of primary biliary cirrhosis.