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| |  High Doses of Ursodeoxycholic Acid Leads to Poorer Outcomes in Primary Sclerosing Cholangitis HOBOKEN, NJ -- August 19, 2009 -- A recently ceased study, published in the journal Hepatology, determined that patients with primary sclerosing cholangitis (PSC) who were treated with high-dose ursodeoxycholic acid (UDCA) had poorer clinical results compared with those who did not receive the therapy. More patients in the UDCA group developed oesophageal or gastric varices, died or became eligible for liver transplantation compared with the placebo group despite improvement in liver tests. Keith Lindor, MD, Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota, and colleagues enrolled 150 adult patients with PSC across 7 sites in the United States over a 3-year period. Half of the participants in the double-blind controlled trial were given high-dose UDCA 28 to 30 mg/kg/day, while the others received a placebo. Liver biopsy and imaging of the bile ducts were performed to monitor patients' response to the therapy. The primary outcome measure was development of cirrhosis, varices, cholangiocarcinoma, meeting minimal listing criteria for transplant, liver transplantation or death. "Our results showed patients on UDCA had a 2.1 times greater chance for death, transplantation or meeting minimal listing criteria than for those in the placebo group," explained researchers. Patients treated with UDCA were more likely to suffer serious adverse effects from the therapy then those who did not receive treatment (63% vs 37%). Previous studies projected UDCA to be a safe and beneficial therapy. According to researchers, the US Food and Drug Administration (FDA) approved a UDCA dose of 13 to 15 mg/kg/day for patients with primary biliary cirrhosis and those patients did not suffer more adverse effects when treated with higher doses of the drug up to 25 or 30 mg/kg/day. Pilot studies in patients with PSC using doses ranging from 17 to 25 mg/kg/day did not have an increased risk of adversities. "The findings in our study were surprising and quite unanticipated," said Dr. Lindor. "It is unclear how a drug that has a reputation for such safety would have these paradoxical effects in this condition." Researchers speculate that higher doses of UDCA allowed unabsorbed drug to enter the colon, modifying into hepatotoxic bile acids and recommend further evaluation of this theory. "At this time, UDCA in a dose of 25 to 30 mg/kg/day should not be used due to the increased risk to PSC patients," advises Dr. Lindor. "We hope a safe and effective therapy for patients with PSC will be developed, but high-dose UDCA cannot be recommended." SOURCE: Wiley Blackwell
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