High-dose ursodeoxycholic acid in primary sclerosing cholangitis:: A 5-year multicenter, randomized, controlled study

Background & Aims: There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease. Methods: A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey. Results: The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and I placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results. Conclusions: This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.