title: High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis.
abstract: 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 high-dose 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 = 76) and placebo (n = 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 = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]).
  
  
  CONCLUSIONS
  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.
authors: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. lindor.keith@mayo.edu
authors: Keith D
authors: KD
authors: Lindor
authors: Kris V
authors: KV
authors: Kowdley
authors: Velimir A C
authors: VA
authors: Luketic
authors: M Edwyn
authors: ME
authors: Harrison
authors: Timothy
authors: T
authors: McCashland
authors: Alex S
authors: AS
authors: Befeler
authors: Denise
authors: D
authors: Harnois
authors: Roberta
authors: R
authors: Jorgensen
authors: Jan
authors: J
authors: Petz
authors: Jill
authors: J
authors: Keach
authors: Jody
authors: J
authors: Mooney
authors: Carol
authors: C
authors: Sargeant
authors: Julie
authors: J
authors: Braaten
authors: Tamara
authors: T
authors: Bernard
authors: Debra
authors: D
authors: King
authors: Ellen
authors: E
authors: Miceli
authors: Jeff
authors: J
authors: Schmoll
authors: Tanya
authors: T
authors: Hoskin
authors: Prabin
authors: P
authors: Thapa
authors: Felicity
authors: F
authors: Enders
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015209:Cholangitis, Sclerosing / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008111:Liver Function Tests; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin