Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis

Background Ursodeoxycholic acid (UDCA) is the only approved treatment for p rimary biliary cirrhosis, but its effect on disease progression and surviva l is uncertain. The aim of this study was to clarify the efficacy of UDCA i n primary biliary cirrhosis. Methods A systematic review, including the use of metaanalysis, was done fo r the randomised and switch-over phases of trials comparing UDCA with place bo, obtained from Medline and Embase databases, and from manual searches de rived from review articles and abstracts of major international meetings. A ll trials had more than a mean of 6 months' follow-up and only included pat ients with primary biliary cirrhosis (PBC) according to established diagnos tic criteria. Findings 17 relevant articles were identified: 11 randomised controlled tri als, including 1272 patients, and six reports of the switch-over phases. UC DA had a favourable effect on liver biochemistry in most of the studies but not on symptoms or the progression of histological stage; two studies did not assess survival, liver transplantation, or complications of liver disea se. Meta-analysis showed no difference between UDCA and placebo in the inci dence of death (odds ratio 1.21, 95% CI 0.71-2.04), liver related death (0. 72, 0.22-2.32), liver transplantation (1.27, 0.78-2.07), death or liver tra nsplantation (1.26, 0.87-1.82), and in the development of complications of liver disease (1.11, 0.64-1.92). With the primary end point defined by the authors (a combined end point in three studies, and death or liver transpla ntation in the others) an odds ratio of 1.53 (0.97-2.42) was obtained. Asse ssment of the switch-over phases, during which there was a longer follow-up , did not change the results of the metaanalysis. Interpretation Published randomised controlled trials of UDCA do not show e vidence of therapeutic benefit in PBC and its use as standard therapy needs to be re-examined.