title: High-dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis.
abstract: BACKGROUND
  Ursodeoxycholic acid (UDCA) in a dose of 28-30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients.
  
  
  OBJECTIVE
  To compare the risk of adverse clinical endpoints in patients with varying disease status.
  
  
  METHODS
  We reviewed records from patients previously enrolled in a study evaluating the effects of high dose (28-30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histological stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, oesophageal varices and cholangiocarcinoma was sought.
  
  
  RESULTS
  A total of 150 patients were included of whom 49 patients developed endpoints. There was an increased development of endpoints among patients using UDCA vs. placebo (14 vs. 4, P=0.0151) with early histological disease (stage 1-2, n=88) but not with late stage (stage 3-4, n=62) disease (17 vs. 14, P=0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, P=0.0008) with normal bilirubin levels (total bilirubin ≤1.0 mg/dL) but not in patients with elevated bilirubin levels (15 vs. 16, P=0.6018). Among patients not reaching endpoints 31.7% had normalisation of their alkaline phosphatase levels when compared to 14.3% in patients who reached endpoints (P=0.073).
  
  
  CONCLUSIONS
  The increased risk of adverse events with UDCA treatment when compared with placebo is only apparent in patients with early histological stage disease or normal total bilirubin.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. imam.mohamad@mayo.edu
authors.forename: M H
authors.initials: MH
authors.lastname: Imam
authors.forename: E
authors.initials: E
authors.lastname: Sinakos
authors.forename: A A
authors.initials: AA
authors.lastname: Gossard
authors.forename: K V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: V A C
authors.initials: VA
authors.lastname: Luketic
authors.forename: M
authors.initials: M
authors.lastname: Edwyn  Harrison
authors.forename: T
authors.initials: T
authors.lastname: McCashland
authors.forename: A S
authors.initials: AS
authors.lastname: Befeler
authors.forename: D
authors.initials: D
authors.lastname: Harnois
authors.forename: R
authors.initials: R
authors.lastname: Jorgensen
authors.forename: J
authors.initials: J
authors.lastname: Petz
authors.forename: J
authors.initials: J
authors.lastname: Keach
authors.forename: A C
authors.initials: AC
authors.lastname: DeCook
authors.forename: F
authors.initials: F
authors.lastname: Enders
authors.forename: K D
authors.initials: KD
authors.lastname: Lindor
mesh_terms: D000328:Adult; D001663:Bilirubin / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000009:adverse effects*; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D001663:Bilirubin