Background: Primary biliary cirrhosis is a rare autoimmune liver disease and an effective treatment has been difficult to establish. Some randomised clinical trials have found an effect of ursodeoxycholic acid for primary biliary cirrhosis.
Objectives: Evaluate the beneficial effects and adverse effects of peroral ursodeoxycholic acid for primary biliary cirrhosis versus placebo or no intervention.
Search strategy: The Controlled Trials Register of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, EMBASE and the full text of the identified studies were searched until April 2001. The electronic searches were done by entering the search terms 'ursodeoxycholic acid', 'UDCA', 'primary biliary cirrhosis', and 'PBC'.
Selection criteria: Randomised clinical trials evaluating ursodeoxycholic acid administered perorally at any dose versus placebo or no intervention in patients with primary biliary cirrhosis diagnosed by any method. Only trials using an adequate method for randomisation were included, regardless of blinding and language.
Data collection and analysis: The methodologic quality of the randomised clinical trials was evaluated by components and the Jadad-score. The following outcomes were extracted: mortality, liver transplantation, pruritus, other clinical symptoms (jaundice, portal pressure, (bleeding) oesophageal varices, ascites, hepatic encephalopathy, hepato-renal syndrome, autoimmune conditions), liver biochemistry, liver function, liver biopsy findings, quality of life, and adverse events. All analyses were performed according to the intention-to-treat method.
Main results: A total of 16 randomised clinical trials evaluating ursodeoxycholic acid against placebo (n = 15) or no intervention (n = 1) in 1422 patients were identified. The median Jadad-score was 3 (range 1-5). A number of trials described as double blind had problems with the blinding. Neither mortality (odds ratio = 0.94; 95% confidence interval (CI) 0.60 to 1.48), liver transplantation (odds ratio = 0.83; 95% CI 0.52 to 1.32), mortality or liver transplantation (odds ratio = 0.90; 95% CI 0.65 to 1.26), pruritus, fatigue, autoimmune conditions, quality of life, liver histology, or portal pressure were significantly affected by ursodeoxycholic acid (given in doses of 8-15 mg/kg/day for three months to five years). However, ursodeoxycholic acid significantly (P < 0.05) reduced ascites, jaundice, and biochemical variables such as serum bilirubin and liver enzymes. Ursodeoxycholic acid was not significantly associated with adverse events. Including data after patients had been switched onto open label ursodeoxycholic acid confirmed the findings regarding the lack of a significant effect of ursodeoxycholic acid on mortality and mortality or liver transplantation. A significant (P = 0.04) effect was, however, observed on the incidence of liver transplantation (odds ratio = 0.68; 95% CI 0.48 to 0.98).
Reviewer's conclusions: Ursodeoxycholic acid has a marginal therapeutic effect for primary biliary cirrhosis. On the positive side, ursodeoxycholic acid has few side effects. The general usage of ursodeoxycholic acid for primary biliary cirrhosis needs reevaluation.