N Engl J Med 1997 Mar 6;336(10):691-5

Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing
Cholangitis-Ursodeoxycholic Acid Study Group

Lindor KD

Mayo Foundation, Rochester, MN 55905, USA.

Abstract

BACKGROUND: There is no satisfactory medical therapy for patients with primary
sclerosing cholangitis. Ursodiol (ursodeoxycholic acid) benefits patients with
primary biliary cirrhosis, another cholestatic liver disease. METHODS: From May
1989 to July 1995, we enrolled 105 patients with well-documented primary
sclerosing cholangitis in a randomized, double-blind study comparing ursodiol
(13 to 15 mg per kilogram of body weight per day in divided doses) with placebo.
The primary outcome was the time to treatment failure, defined as death; liver
transplantation; histologic progression by two stages (of four) or progression
to cirrhosis; the development of varices, ascites, or encephalopathy; sustained
quadrupling of the serum bilirubin concentration; marked worsening of fatigue or
pruritus; inability to tolerate the drug; or voluntary withdrawal from the
study. RESULTS: We analyzed data on the 51 patients in each group with at least
3 months of follow-up; the median follow-up was 2.2 years. There was no
significant difference between the groups in time to treatment failure (relative
risk of treatment failure in the ursodiol group, 1.01; 95 percent confidence
interval, 0.6 to 1.7). During the first two years of follow-up, treatment was
unsuccessful in 17 of 32 patients (53 percent) in the placebo group and 16 of 31
(52 percent) in the ursodiol group. There were also no differences in time to
treatment failure for patients with early-stage disease or in time to liver
transplantation. Ursodiol, but not placebo, was associated with improvement in
serum alkaline phosphatase, aspartate aminotransferase, bilirubin, and albumin
levels at one and two years. CONCLUSIONS: In a group of patients with
well-defined primary sclerosing cholangitis, ursodiol provided no clinical
benefit