Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of highdose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n โซุโฌ 76) and placebo (n โซุโฌ 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P โซุโฌ 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (HEPATOLOGY 2009;50:808-814.)
See Editorial on Page 671 P rimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by fibrosing inflammation and destruction of the extrahepatic and/or intrahepatic bile ducts. The disease is slowly progressive, usually leading to biliary cirrhosis, portal hypertension, and liver failure over a 10to 15-year period. 2 PSC is one of the most common adult cholestatic liver diseases and is an important indication for liver transplantation in adults in the United States. At least 70% of cases of PSC are associated with chronic inflammatory bowel disease, usually ulcerative colitis. There are no reports of effective medical therapy for PSC at this time. Several potential treatments have been evaluated in both controlled and uncontrolled trials, including methotrexate, corticosteroids, cyclosporin, tacrolimus, and colchicine but none have been found to be effective. Ursodeoxycholic acid (UDCA) has been tested in a randomized controlled trial of 105 patients at a dose of 13 to 15 mg/kg/day. 9 There was biochemical improvement and a trend toward an improvement to time of treatment failure was noted, although the difference was Abbreviations: PSC, primary sclerosing cholangitis; UDCA, ursodeoxycholic acid.