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.
RCT Entities:
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 PSCpatients. 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.
Authors: Anna Baghdasaryan; Thierry Claudel; Astrid Kosters; Judith Gumhold; Dagmar Silbert; Andrea Thüringer; Katharina Leski; Peter Fickert; Saul J Karpen; Michael Trauner Journal: Gut Date: 2010-04 Impact factor: 23.059