High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective

Background/Aims Ursodeoxycholic acid (UDCA) has been shown to improve serum liver tests in primary sclerosing cholangitis (PSC), but controlled trials have shown inconsistent effects on liver histology, and did not reveal a survival benefit. This pilot, randomised dose-ranging trial attempted to determine whether further enrichment of the bile acid pool with UDCA would lead to an improvement in outcome for PSC patients. Methods Thirty-one patients with PSC were randomised to treatment with either 10 mg/kg (low dose), 20 mg/kg (standard dose) or 30 mg/kg (high dose) daily of UDCA for 2 years. Patients were assessed every 12 weeks and underwent liver biopsy at the beginning and end of the trial. Results Serum liver tests improved in all groups taking UDCA. Survival probability at 1–4 years as evaluated by the Mayo risk score tended to improve for all patients and significantly improved for the high dose group (p < 0.02). Only 3 (10%) of all patients had a Ludwig score showing histological deterioration over the trial period. Conclusions High dose UDCA is well-tolerated and is associated with an improvement in survival probability. A trend towards stability/improvement in histological stage was also observed. This treatment appears to be effective for PSC and deserves further evaluation. Ursodeoxycholic acid (UDCA) has been shown to improve serum liver tests in primary sclerosing cholangitis (PSC), but controlled trials have shown inconsistent effects on liver histology, and did not reveal a survival benefit. This pilot, randomised dose-ranging trial attempted to determine whether further enrichment of the bile acid pool with UDCA would lead to an improvement in outcome for PSC patients. Thirty-one patients with PSC were randomised to treatment with either 10 mg/kg (low dose), 20 mg/kg (standard dose) or 30 mg/kg (high dose) daily of UDCA for 2 years. Patients were assessed every 12 weeks and underwent liver biopsy at the beginning and end of the trial. Serum liver tests improved in all groups taking UDCA. Survival probability at 1–4 years as evaluated by the Mayo risk score tended to improve for all patients and significantly improved for the high dose group (p < 0.02). Only 3 (10%) of all patients had a Ludwig score showing histological deterioration over the trial period. High dose UDCA is well-tolerated and is associated with an improvement in survival probability. A trend towards stability/improvement in histological stage was also observed. This treatment appears to be effective for PSC and deserves further evaluation.