DR CHAPMANS' STUDY/A Preliminary Trial of High-Dose Ursodeoxycholic Acid...

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Published online 15 October 2001GASTROENTEROLOGY 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. Get your FREE download of MSN Explorer at http://explorer.msn.com