A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis

Forty-six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo-controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well-matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin {MCD 5 μmol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 μmol/L (95% CI 1 to 9) at 2 years}, alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long-term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 μmol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant. Ursodeoxycholic acid did not generally influence stage progression or histological features, although a smaller percentage of non-cirrhotic patients were documented as having developed cirrhosis on UDCA compared to placebo (14 vs 57%) over the 2 years. There appeared to be no consistent effect on pruritus and general well-being. The medication was well-tolerated and safe. In conclusion, UDCA appears to have beneficial effects on some serum biochemical markers in primary biliary cirrhosis and so may have a role in retarding disease progression. It could be useful in combination with an immunosuppressive or an anti-fibrotic agent.