A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis.
OBJECTIVE
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.
Mitchell
S A
SA
Department of Gastroenterology, Oxford Radcliffe Hospital, Oxford, England, UK.
Bansi
D S
DS
Hunt
N
N
Von Bergmann
K
K
Fleming
K A
KA
Chapman
R W
RW
D000328:Adult; D000368:Aged; D002648:Child; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002758:Cholangiography; D015209:Cholangitis, Sclerosing / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002792:Cholestyramine Resin / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology; D008111:Liver Function Tests; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D002792:Cholestyramine Resin; D014580:Ursodeoxycholic Acid