A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis

Background & Aims: Ursodeoxycholic acid (UDCA) is used for the treatment of cholestatic liver diseases including primary biliary cirrhosis (PBC) for w hich it has a positive effect on laboratory values, may delay the developme nt of liver failure and prolong the transplant-free disease period. Standar d doses of UDCA (8-15 mg/kg daily) have been shown to be ineffective in the treatment of primary sclerosing cholangitis (PSC). We report on the findin gs (clinical, biochemical, histological, and cholangiographic) and side eff ects of a 2-year double-blind placebo-controlled preliminary study of high- dose UDCA in PSC patients. Methods: Twenty-six patients with PSC were rando mized to high-dose (20 mg/kg daily) UDCA or placebo. Cholangiography and li ver biopsy were performed at entry and after 2 years. Symptoms, clinical si gns, and liver biochemical tests were recorded at 3 monthly intervals. Resu lts: High-dose UDCA did not influence symptoms, but there was a significant improvement in liver biochemistry (serum alkaline phosphatase, P = 0.03; g amma -glutamyl transferase, P = 0.01) and a significant reduction in progre ssion in cholangiographic appearances (P = 0.015) and liver fibrosis as ass essed by disease staging (P = 0.05). In the treatment group, a significant increase in total bile acids and saturation with UDCA > 70% confirmed patie nt compliance. No significant side effects were reported. Conclusions: High -dose UDCA may be of clinical benefit in PSC, but trials with a larger numb er of participants and of longer duration are required to establish whether the effect of high-dose UDCA on liver biochemistry, histology, and cholang iography in patients with PSC is translated into improved long-term surviva l.