URSODEOXYCHOLIC ACID FOR SYMPTOMATIC PRIMARY BILIARY-CIRRHOSIS - PRELIMINARY-ANALYSIS OF A DOUBLE-BLIND MULTICENTER TRIAL

The administration of ursodeoxycholic acid, a hydrophilic bile acid not hepatotoxic to humans, has been suggested for treatment of primary biliary cirrhosis to improve cholestasis and reduce hepatocellular damage. Efficacy of treatment has been studied mainly in patients with asymptomatic or early-stage disease. In January 1988, to establish the efficacy and safety of ursodeoxycholic acid in a population with more severe disease, we started a multicenter, double-blind, placebo-controlled trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigned to ursodeoxycholic acid, 500 mg daily (corresponding to about 8.7 mg/kg body weight in these patients), and 44 to a placebo. As planned at the beginning of the study, a preliminary analysis was performed when all patients had been followed for at least 6 months (33 patients up to 12 months). Pruritus, self-evaluated by the patients, and cholestyramine consumption, as recorded in a diary, decreased significantly (p < 0.01) in both groups. In patients who initially had abnormal levels, serum bilirubin decreased significantly (p < 0.05) in the ursodeoxycholic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the placebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AST (p < 0.001); serum prealbumin (p < 0.05); IgG (p < 0.0 1) and IgM (p < 0.0 1) levels. The positive effects of ursodeoxycholic acid administration on serum bilirubin, the most important prognostic factor in primary biliary cirrhosis, and on liver protein synthesis suggest that ursodeoxycholic acid may be useful for patients with more advanced disease than those so far included in therapeutic trials.