Results of long-term ursodiol treatment for patients with primary biliary cirrhosis.
OBJECTIVE: When ursodeoxycholic acid (UDCA) is used for the treatment of primary biliary cirrhosis, it has been associated with biochemical improvement, histological stability, reduced risk of esophageal varices, and increased survival free of transplantation. There is limited information available about the long-term outcome of these patients with primary biliary cirrhosis on UDCA treatment. To address this, we reviewed the long-term results from patients enrolled in our original randomized study with up to 12 yr of follow-up. METHODS: From April 1988 to March 1992, a total of 180 patients were enrolled into a randomized, controlled trial evaluating UDCA (n = 89) versus placebo (n = 91). When the randomized portion of the study concluded in May 1992, patients were switched to active medication and followed for up to an additional 8 yr. RESULTS: Twenty-eight patients originally assigned to UDCA and 42 patients originally assigned to placebo have died or undergone transplantation. The patients who died or were transplanted were more histologically advanced at entry (p < 0.001). Seventy-six of the remaining 110 patients return for regular follow-up; mailed questionnaires were returned by an additional 25 patients, and nine patients have been lost to follow-up. Twenty-two of the 76 patients we follow have normal liver tests (ALP, bilirubin, and AST). Patients with normal liver tests had significantly lower levels of ALP and AST at baseline (p < 0.05), but did not differ in histological stage or total bilirubin from those with persistently abnormal tests. CONCLUSIONS: UDCA appears to be of most benefit when instituted in early stage disease. Although a substantial percentage of patients will achieve biochemical normalization on UDCA alone, there is a continued need for therapeutic options for others who have less complete biochemical responses.