High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis

OBJECTIVES: To assess the tolerability and efficacy of high-dose (25-30 mg/ kg per day) ursodeoxycholic acid (UDCA) in patients with primary sclerosing cholangitis (PSC). METHODS: Thirty patients with PSC were enrolled in this pilot study and tre ated for 1 yr. Changes in the Mayo risk score at 1 yr of treatment and proj ected survival at 4 yr were compared with that observed in patients randomi zed to placebo (n = 52) or UDCA (n = 53) at a dose of 13-15 mg/kg per day. RESULTS: A marked improvement in serum alkaline phosphatase activity (1265 +/- 172 vs 693 +/- 110 U/L, p < 0.001), AST (161 +/- 037 vs 77 +/- 13 U/L, p = 0.001), albumin (4.0 +/- 0.1 vs 4.2 +/- 0.1 g/dl, p = 0.03), and total bilirubin (1.6 +/- 0.3 vs 1.3 +/- 0.2 mg/dl, p = 0.1) occurred at 1 yr of t herapy with high-dose UDCA. Changes in the Mayo risk score after 1 yr of tr eatment were significantly different among the three groups (p < 0.001), an d these changes would be translated into a significantly different expected survival at 4 yr (p = 0.05). This expected survival at 4 yr was significan tly different between placebo and the dose of 25-30 mg/kg per day (p = 0.04 ), but not between placebo and the dose of 13-15 mg/kg per day (p = 0.4). H igh-dose UDCA was well tolerated. CONCLUSIONS: UDCA at a dose of 25-30 mg/kg per day may be of benefit for pa tients with PSC, and this regimen deserves further evaluation in a long-ter m, randomized, placebo-controlled trial. (C) 2001 by Am. Cell. of Gastroent erology.