Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials.

OBJECTIVES

The effect of ursodeoxycholic acid (UDCA) treatment on survival and liver histological progression of primary biliary cirrhosis (PBC) remains uncertain. The aim of this study is to assess the long-term efficacy of mid-dose UDCA treatment for PBC.

METHODS

Electronic databases including Medline, Embase, Cochrane controlled trials register, Science Citation Index, and PUBMED (updated to Nov 2005), and manual bibliographical searches were conducted. A meta-analysis of all long-term randomized controlled trials (RCTs) comparing mid-dose UDCA with placebo or no treatment was performed.

RESULTS

Seven RCTs and six reports of their extended follow-up including 1,038 patients were assessed. UDCA could significantly improve liver biochemistry, but had no effect on pruritus and fatigue. UDCA could delay the progression of PBC, especially for early-stage patients. Meta-analysis of the seven RCTs including their extended follow-up showed a significant reduction of the incidence of liver transplantation (OR 0.65, p = 0.01), and a marginally significant reduction of the rate of death or liver transplantation (fixed-effect model: OR 0.76, p = 0.05; random-effect model: OR 0.77, p = 0.3) in the UDCA group, except death (OR 1.01, p = 1). In the sensitivity analyses, which included studies administrating placebo as control, long-term studies (> or = 48 months), or large size studies (total number of patients > or = 100), we all found long-term treatment with UDCA could significantly reduce the incidence of liver transplantation, and death or liver transplantation.

CONCLUSIONS

Long-term treatment with mid-dose UDCA can improve liver biochemistry and survival free of liver transplantation in patients with PBC. In addition, UDCA therapy can delay the histological progression in the early-stage patients.