title: Biochemical criteria at 1 year are not robust indicators of response to ursodeoxycholic acid in early primary biliary cirrhosis: results from a 29-year cohort study.
abstract: BACKGROUND
  In primary biliary cirrhosis (PBC), biochemical criteria at 1 year are considered surrogates of response to ursodeoxycholic acid (UDCA). However, due to the slow natural history of PBC, evaluation at 1 year may be suboptimal to assess the therapeutic response, particularly in early disease.
  
  
  OBJECTIVE
  To determine whether evaluation of biochemical criteria at 1 year is a reliable surrogate of UDCA response in early PBC.
  
  
  METHODS
  We analysed the prospectively collected data of 215 patients (untreated = 129; UDCA-treated = 86) with early PBC (normal baseline bilirubin/albumin) and a median follow-up of 8 years (range: 1-29.1). The 1-year attainment rates of the Barcelona, Paris-I, Paris-II and Toronto definitions, and their predictive relevance for a poor outcome (death, transplantation, complications of cirrhosis), were assessed either as a result of UDCA or no treatment. Independent associations with attaining each UDCA response definition were identified by multivariate analysis.
  
  
  RESULTS
  Untreated patients displayed 1-year biochemical features compatible with 'treatment response' at rates (Barcelona: 36.4%, Paris-I: 66.7%, Toronto: 59.7%, Paris-II: 40.3%) similar to those obtained under UDCA. Depending on the definition, baseline ALP≤3xULN (OR: 4.80-35.90), AST≤2xULN (OR: 5.63-9.34) and early histological stage (OR: 3.67-3.87) were the stronger predictors for attaining the criteria. UDCA treatment was associated with attaining Barcelona (OR = 2.16) and Paris-II (OR = 2.84), but not Paris-I, and not Toronto definition when excluding late histological cases. Paris-I criteria were significantly predictive of long-term outcomes (HR = 2.83) in untreated patients.
  
  
  CONCLUSIONS
  In early PBC, biochemical criteria at 1 year reflect severity of the disease rather than the therapeutic response to UDCA.
authors.affiliation: The Royal Free Sheila Sherlock Liver Centre and UCL Institute of Liver and Digestive Health, Royal Free Hospital and UCL, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Papastergiou
authors.forename: E A
authors.initials: EA
authors.lastname: Tsochatzis
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez-Peralvarez
authors.forename: M
authors.initials: M
authors.lastname: Rodriquez-Peralvarez
authors.forename: E
authors.initials: E
authors.lastname: Thalassinos
authors.forename: G
authors.initials: G
authors.lastname: Pieri
authors.forename: P
authors.initials: P
authors.lastname: Manousou
authors.forename: G
authors.initials: G
authors.lastname: Germani
authors.forename: C
authors.initials: C
authors.lastname: Rigamonti
authors.forename: V
authors.initials: V
authors.lastname: Arvaniti
authors.forename: S
authors.initials: S
authors.lastname: Karatapanis
authors.forename: A K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D000418:Albumins; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D001663:Bilirubin