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

Gastroenterology. 2005 Nov;129(5):1464-72. doi: 10.1053/j.gastro.2005.08.017.


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 1 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Bile Acids and Salts / blood
  • Cholagogues and Choleretics / administration & dosage*
  • Cholagogues and Choleretics / adverse effects
  • Cholangitis, Sclerosing / drug therapy*
  • Cholangitis, Sclerosing / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Failure / mortality
  • Liver Failure / surgery
  • Liver Transplantation
  • Male
  • Middle Aged
  • Patient Dropouts
  • Quality of Life
  • Survival Analysis
  • Treatment Outcome
  • Ursodeoxycholic Acid / administration & dosage*
  • Ursodeoxycholic Acid / adverse effects


  • Bile Acids and Salts
  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid
  • Alanine Transaminase
  • Alkaline Phosphatase