title: High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.
abstract: OBJECTIVE
  Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28-30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC.
  
  
  METHODS
  Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer.
  
  
  RESULTS
  Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30-20.10, P=0.02).
  
  
  CONCLUSIONS
  Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.
authors.affiliation: Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Eaton
authors.forename: Marina G
authors.initials: MG
authors.lastname: Silveira
authors.forename: Darrell S
authors.initials: DS
authors.lastname: Pardi
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Sinakos
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Velimir A C
authors.initials: VA
authors.lastname: Luketic
authors.forename: M Edwyn
authors.initials: ME
authors.lastname: Harrison
authors.forename: Timothy
authors.initials: T
authors.lastname: McCashland
authors.forename: Alex S
authors.initials: AS
authors.lastname: Befeler
authors.forename: Denise
authors.initials: D
authors.lastname: Harnois
authors.forename: Roberta
authors.initials: R
authors.lastname: Jorgensen
authors.forename: Jan
authors.initials: J
authors.lastname: Petz
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lindor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002635:Chenodeoxycholic Acid / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy*; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008095:Lithocholic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D002756:Cholagogues and Choleretics; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid