Multicentre randomized placebo-controlled trial of ursodeoxycholic acid with or without colchicine in symptomatic primary biliary cirrhosis

Aim: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cir rhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilir ubin exceeding 2 mg/mL. Methods: A total of 90 patients were randomly assigned to ursodeoxycholic a cid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid a t the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritu s, bilirubin, and Mayo score. All patients underwent clinical, ultrasonogra phic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 m onths. In a sub-group of patients without cirrhosis, who consented, liver b iopsy was repeated at the end of the study. Results: The number of treatment failures (i.e. dead, orthotopic liver tran splantation (OLT), complications of cirrhosis, doubling of bilirubin, untre atable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of imp rovement of liver enzymes related to cholestasis and cytolysis and of ameli oration of pruritus. The Mayo score values increased less above the baselin e values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C gro up, whereas no changes in these histological scores were observed in the UD CA group. Conclusions: The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but signific ant reduction of disease progress.