Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial

Background/Aim: Ursodeoxycholic acid in doses of 13–15 mg•kg−1•day−1, is a safe and cost-effective treatment for patients with primary biliary cirrhosis. However, very limited information exists regarding the most appropriate dose of ursodeoxycholic acid. The aim of the study was to compare three dosages of ursodeoxycholic acid with respect to changes in liver biochemistries, Mayo risk score, biliary enrichment with ursodeoxycholic acid and side effects over at least a 1-year period. Methods: A total of 155 patients were randomized to receive low- (5–7 mg•kg−1•day−1), standard-(13–15 mg•kg−1•day−1), and high- (23–25 mg•kg−1•day−1) doses of ursodeoxycholic acid. Results: The improvements in alkaline phosphatase (p=0.0001), aspartate aminotransferase (p=0.0001), Mayo risk score (p=0.002), and ursodeoxycholic acid enrichment (p=0.0001) were significantly greater in the standard- and high-dose groups compared to the low-dose group, but not between the standard- and high-dose groups. Changes in serum bilirubin were similar between the three groups (p=0.07). No significant effects on symptoms were noted with any dose. No patients discontinued ursodeoxycholic acid because of side effects or toxicity. Conclusions: Ursodeoxycholic acid in doses of 5–25 mg•kg−1•day−1 is safe and well tolerated. The dose of 13–15 mg•kg−1•day−1 appears to be the preferred dose for patients with primary biliary cirrhosis.