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

Am J Gastroenterol. 2006 Jul;101(7):1529-38. doi: 10.1111/j.1572-0241.2006.00634.x.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholagogues and Choleretics / administration & dosage
  • Cholagogues and Choleretics / therapeutic use*
  • Humans
  • Liver Cirrhosis, Biliary / drug therapy*
  • Outcome Assessment, Health Care
  • Randomized Controlled Trials as Topic
  • Ursodeoxycholic Acid / administration & dosage
  • Ursodeoxycholic Acid / therapeutic use*


  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid