title: Reduction in alkaline phosphatase is associated with longer survival in primary sclerosing cholangitis, independent of dominant stenosis.
abstract: BACKGROUND
  Alkaline phosphatase (ALP) is an important serum marker in primary sclerosing cholangitis (PSC). Patients with obstruction of the large bile ducts due to dominant strictures (DS) are a special, clinically important phenotype.
  
  
  OBJECTIVE
  To determine the impact of ALP reduction on liver transplantation-free survival in PSC patients with DS.
  
  
  METHODS
  Prospective cohort study in 215 PSC patients. We performed subgroup analysis for patients without DS (no DS, n = 84), DS at first presentation (DS early, n = 72) and development of DS during the course of the study (DS late, n = 59). We evaluated two scores of ALP reduction. ALP reduction 1 was defined as ALP normalisation, 50% reduction compared with baseline values, or reduction below 1.5 times of upper limit of normal (ULN) within 6 months. ALP reduction 2 was defined as ALP reduction below 1.5 times of ULN within 12 months.
  
  
  RESULTS
  Of the patients, 59.5% reached an ALP reduction 1 and 56.7% according to ALP reduction 2. Achievement of each score was associated with longer transplantation-free survival in all three groups (ALP reduction 1: no DS P = 0.001; DS early P < 0.001; DS late P = 0.022; ALP reduction 2: no DS P = 0.014; DS early P = 0.001; DS late P = 0.002). Cox-regression analysis revealed each score as an independent predictor for improved transplantation-free survival (ALP reduction 1 and 2 P < 0.001 each). We further analysed previously published scores of ALP improvement in PSC showing also improved survival in patients with ALP normalisation or a reduction below 1.5 times of ULN (P = 0.003, P = 0.001, respectively), whereas the score determined by 40% reduction did not show significant differences in survival (P = 0.55).
  
  
  CONCLUSIONS
  Reduction in alkaline phosphatase values within the first year is associated with improved transplantation-free survival in patients with primary sclerosing cholangitis independent of the presence of dominant strictures. Alkaline phosphatase might be an adequate surrogate marker for outcome assessment in clinical studies both for patients with and without dominant strictures.
authors.affiliation: Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rupp
authors.forename: A
authors.initials: A
authors.lastname: Rössler
authors.forename: E
authors.initials: E
authors.lastname: Halibasic
authors.forename: P
authors.initials: P
authors.lastname: Sauer
authors.forename: K-H
authors.initials: KH
authors.lastname: Weiss
authors.forename: K
authors.initials: K
authors.lastname: Friedrich
authors.forename: A
authors.initials: A
authors.lastname: Wannhoff
authors.forename: A
authors.initials: A
authors.lastname: Stiehl
authors.forename: W
authors.initials: W
authors.lastname: Stremmel
authors.forename: M
authors.initials: M
authors.lastname: Trauner
authors.forename: D N
authors.initials: DN
authors.lastname: Gotthardt
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000150:complications* / Q000201:enzymology*; D003251:Constriction, Pathologic / Q000097:blood / Q000150:complications* / Q000201:enzymology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase