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

Background/Aims: The aim of this study was to assess the efficacy of ursode oxycholic 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 U DCA/kg/day or placebo. Patients underwent a complete history, physical exam ination, liver chemistries, immunological determinations and liver biopsy a t entry and at the end of the trial, which lasted for at least 2 years. Pat ients were seen every 3 months and the median follow-up was 3.4 years (rang e 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 treatm ent was associated with decreases in alkaline phosphatase, gammaglutamyl tr ansferase, alanine aminotransferase, and cholesterol levels, effects which were conspicuous after 3 months of treatment and remained similar during th e follow-up. During the study 31 patients (10 receiving UDCA and 21 placebo ) discontinued the trial because of noncompliance (n=11), voluntary withdra wal (n=19) or adverse effects (n=1), Treatment failure (death or liver tran splantation) 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 o r placebo. Histological analysis indicates that UDCA improved portal inflam mation and prevented histological stage progression. By contrast, histologi cal stage as well as ductular proliferation and ductopenia progressed in pa tients receiving placebo. Conclusions: Although UDCA treatment did not significantly affect time to d eath 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.