A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis

Gastroenterology. 2001 Oct;121(4):900-7. doi: 10.1053/gast.2001.27965.


Background & aims: Ursodeoxycholic acid (UDCA) is used for the treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) for which it has a positive effect on laboratory values, may delay the development of liver failure and prolong the transplant-free disease period. Standard doses of UDCA (8-15 mg/kg daily) have been shown to be ineffective in the treatment of primary sclerosing cholangitis (PSC). We report on the findings (clinical, biochemical, histological, and cholangiographic) and side effects of a 2-year double-blind placebo-controlled preliminary study of high-dose UDCA in PSC patients.

Methods: Twenty-six patients with PSC were randomized to high-dose (20 mg/kg daily) UDCA or placebo. Cholangiography and liver biopsy were performed at entry and after 2 years. Symptoms, clinical signs, and liver biochemical tests were recorded at 3 monthly intervals.

Results: High-dose UDCA did not influence symptoms, but there was a significant improvement in liver biochemistry (serum alkaline phosphatase, P = 0.03; gamma-glutamyl transferase, P = 0.01) and a significant reduction in progression in cholangiographic appearances (P = 0.015) and liver fibrosis as assessed by disease staging (P = 0.05). In the treatment group, a significant increase in total bile acids and saturation with UDCA >70% confirmed patient compliance. No significant side effects were reported.

Conclusions: High-dose UDCA may be of clinical benefit in PSC, but trials with a larger number of participants and of longer duration are required to establish whether the effect of high-dose UDCA on liver biochemistry, histology, and cholangiography in patients with PSC is translated into improved long-term survival.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Child
  • Cholagogues and Choleretics / therapeutic use*
  • Cholangiography
  • Cholangitis, Sclerosing / diagnostic imaging
  • Cholangitis, Sclerosing / drug therapy*
  • Cholestyramine Resin / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Liver Function Tests
  • Middle Aged
  • Ursodeoxycholic Acid / therapeutic use*


  • Cholagogues and Choleretics
  • Cholestyramine Resin
  • Ursodeoxycholic Acid