URSODIOL FOR THE LONG-TERM TREATMENT OF PRIMARY BILIARY-CIRRHOSIS

Background. Ursodiol (ursodeoxycholic acid) therapy leads to major imp rovements in patients with primary biliary cirrhosis. The benefit of l ong-term treatment is uncertain. Methods. We randomly assigned 145 pat ients with biopsy-proved primary biliary cirrhosis to receive ursodiol (13 to 15 mg per kilogram of body weight per day) (72 patients) or pl acebo (73 patients). After two years of follow-up, because of the bene fit from ursodiol, all patients completing the study received ursodiol in an open trial and were monitored for two more years. The end point s in the assessment of efficacy were as follows: progression of diseas e, as defined by the presence of hyperbilirubinemia, variceal bleeding , ascites, or encephalopathy; liver transplantation or a referral for that procedure; and liver transplantation (or a referral) or death. Re sults. Disease progressed significantly less frequently in the ursodio l group than in the placebo group (P<0.002; relative risk, 0.28; 95 pe rcent confidence interval, 0.12 to 0.63). The probability of liver tra nsplantation or a referral for that procedure and the probability of t ransplantation or death were significantly lower in the group assigned to ursodiol than in the group assigned to placebo (for transplantatio n alone, P = 0.003; relative risk, 0.21; 95 percent confidence interva l, 0.07 to 0.66; for transplantation or death, P = 0.005; relative ris k, 0.32; 95 percent confidence interval, 0.14 to 0.74). High bilirubin levels and, to a lesser extent, signs of cirrhosis at entry into the trial were predictive of disease progression, liver transplantation or a referral, and transplantation or death. Conclusions. Long-term urso diol therapy slows the progression of primary biliary cirrhosis and re duces the need for liver transplantation.