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

The administration of ursodeoxycholic acid, a hydrophilic bile acid no t hepatotoxic to humans, has been suggested for treatment of primary b iliary cirrhosis to improve cholestasis and reduce hepatocellular dama ge. Efficacy of treatment has been studied mainly in patients with asy mptomatic or early-stage disease. In January 1988, to establish the ef ficacy and safety of ursodeoxycholic acid in a population with more se vere disease, we started a multicenter, double-blind, placebo-controll ed trial in patients with symptomatic disease, that is, with pruritus or serum bilirubin exceeding 2 mg/dl. Forty-four patients were assigne d 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 cholestyr amine 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 ursodeoxych olic acid group compared to placebo. After 6 months the following were also significantly better in the ursodeoxycholic acid than in the pla cebo group: a composite weighted biochemical index taking into account the changes in serum bilirubin, alkaline phosphatase, gamma-GT and AS T (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 adminis tration on serum bilirubin, the most important prognostic factor in pr imary biliary cirrhosis, and on liver protein synthesis suggest that u rsodeoxycholic acid may be useful for patients with more advanced dise ase than those so far included in therapeutic trials.