THE CANADIAN MULTICENTER DOUBLE-BLIND RANDOMIZED CONTROLLED TRIAL OF URSODEOXYCHOLIC ACID IN PRIMARY BILIARY-CIRRHOSIS

Ursodeoxycholic acid, a dihydroxyl bile acid nor mally present in huma n beings in minimal amounts, becomes incorporated into the bile salt p ool when taken orally. In cholestasis, bile acids are retained in the liver and are hepatotoxic. Ursodeoxycholic acid is the least-known hep atotoxic bile acid, has choleretic properties and is reported to benef it patients with chronic cholestasis. In a nationwide Canadian control led trial, 222 patients with primary biliary cirrhosis were treated wi th ursodeoxycholic acid (14 mg/kg/body wt/day) or placebo for 24 mo. O nly patients with a diagnosis confirmed by liver biopsy and serum posi tive for antimitochondrial antibodies were enrolled; 88% were symptoma tic on entry. The primary outcome measure was percent change in total serum bilirubin from baseline to final follow-up. Treated patients (11 1) and controls (111) were comparable with regard to age, gender, bioc hemical parameters and liver histological condition. Although treatmen t was not associated with any improvement in symptoms, ursodeoxycholic acid therapy caused the bilirubin to fall significantly within the fi rst 3 mo of therapy (p < 0.001). Significant falls in serum alkaline p hosphatase, aminotransferases, cholesterol and IgM levels were also no ted in the treated group. Improvement in some histological features wa s observed but there was no difference between the groups in the numbe r of patients who reached the endpoints of death or liver transplantat ion. Ursodeoxycholic acid, given to patients with primary biliary cirr hosis, leads to an improvement in serum markers of cholestasis. A larg er sample size is needed to determine whether ursodeoxycholic acid the rapy has a beneficial effect on the survival of patients with primary biliary cirrhosis.