Gastroenterology

Gastroenterology

Volume 121, Issue 4, October 2001, Pages 900-907
Gastroenterology

Liver, Pancreas, and Biliary Tract
A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis☆

https://doi.org/10.1053/gast.2001.27965Get rights and content

Abstract

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; γ-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.

GASTROENTEROLOGY 2001;121:900-907

Section snippets

Patients

All patients with newly diagnosed or established PSC were considered for entry into the trial. The details of the patients are noted in Table 1.The diagnosis of PSC was based on standard clinical, biochemical, histological, and radiological features in the absence of evidence of secondary cholangitis, hepatobiliary malignancy, viral, metabolic, or autoimmune liver disease. In addition to satisfying the cholangiographic criteria1 for the diagnosis of PSC, all eligible patients had a liver biopsy

Results

Thirteen patients were randomly assigned to the treatment group (UDCA at 20 mg/kg body weight daily) and an equal number to the placebo group. All had pretreatment cholangiography and a liver biopsy. Eleven patients in each group had a repeat liver biopsy and cholangiography at 2 years. Two patients, one from each arm of the study, were withdrawn. The first patient was withdrawn from the treatment group after 6 months when he developed a dominant stricture associated with sudden and marked

Discussion

UDCA is widely used in the treatment of cholestatic liver diseases, and it has emerged as a safe and potentially effective drug for the treatment of PBC. In PBC it improves liver biochemistry, some liver histological features, and prolongs survival free of liver transplantation in some but not all studies.36, 37 UDCA appears to exert a number of effects, which may be beneficial in chronic cholestasis: a direct cytoprotective effect38, 39, 40; a choleretic effect by increasing bile flow41, 42;

Acknowledgements

The authors thank Dr. David Smith, Centre for Statistics in Medicine, Institute of Health Sciences, Oxford, England for the statistical analysis.

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    ☆

    Address requests for reprints to: Roger Chapman, M.D., Department of Gastroenterology, Oxford Radcliffe Hospital, Oxford OX3 9DU, England.

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    Copyright © 2001 American Gastroenterological Association. Published by Elsevier Inc. All rights reserved.