title: Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.
abstract: BACKGROUND
  Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients.
  
  
  METHODS
  Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method.
  
  
  RESULTS
  Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment.
  
  
  CONCLUSIONS
  The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.
authors: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
authors: Craig
authors: C
authors: Lammert
authors: Brian D
authors: BD
authors: Juran
authors: Erik
authors: E
authors: Schlicht
authors: Landon L
authors: LL
authors: Chan
authors: Elizabeth J
authors: EJ
authors: Atkinson
authors: Mariza
authors: M
authors: de Andrade
authors: Konstantinos N
authors: KN
authors: Lazaridis
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000009:adverse effects / Q000627:therapeutic use*; D004796:Clinical Enzyme Tests / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011537:Pruritus / Q000139:chemically induced; D012189:Retrospective Studies; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase