A Preliminary Trial of High-Dose Ursodeoxycholic Acid in Primary Sclerosing Chol

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Published online 15 October 2001

GASTROENTEROLOGY 2001;121:900-907

A Preliminary Trial of High-Dose Ursodeoxycholic Acid in Primary

Sclerosing Cholangitis

STEPHEN A. MITCHELL,* DAVINDER S. BANSI,* NICHOLAS HUNT, KLAUS VON

BERGMANN,§ KENNETH A. FLEMING, and ROGER W. CHAPMAN*

*Department of Gastroenterology, and Nuffield Department of Pathology

and Bacteriology, Oxford Radcliffe Hospital, Oxford, England; and

§Abteilung für Klinische Pharmakologie, Rheinische Friedrich-Wilhelms-

Universität, Bonn, Germany

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; -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.