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Patients and patience: the pitfalls of primary biliary cirrhosis trials

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 552–553 (2005)Cite this article

The effect of ursodeoxycholic acid (UDCA) on the natural history of primary biliary cirrhosis (PBC) is controversial. Six large, double-blind, controlled trials have collectively randomized over 1,000 individuals to either UDCA or placebo and followed them for an average of 2 years.1,2,3,4,5,6 In all of the trials, UDCA produced a rapid and impressive improvement in serum alkaline phosphatase, bilirubin, aminotransferases, and IgM levels. Four of the six trials reported beneficial effects of UDCA on histology; however, there was no effect on histologic stage, development of cirrhosis or portal hypertension, or incidence of death or transplantation after 2 years in any of the individual trials.

A combined analysis of three of the trials, including patients switched from placebo to UDCA after 2 years, reported an improvement in transplant-free survival after 4–6 years in the patients originally randomized to UDCA.7 Two independent meta-analyses, however, failed to show any difference between UDCA and placebo in the incidence of death or transplantation, or development of liver disease complications.8,9 Another cohort study compared 140 untreated subjects with 69 UDCA-treated subjects, and found similar disease progression over 5 years in both groups, despite biochemical improvements in the UDCA group.10

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  1. Assistant Professor of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Marlyn J Mayo

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Mayo, M. Patients and patience: the pitfalls of primary biliary cirrhosis trials. Nat Rev Gastroenterol Hepatol 2, 552–553 (2005). https://doi.org/10.1038/ncpgasthep0360

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