title: Improvement of serum alkaline phosphatase to <1.5 upper limit of normal predicts better outcome and reduced risk of cholangiocarcinoma in primary sclerosing cholangitis.
abstract: OBJECTIVE
  Normalization of serum alkaline phosphatase (SAP) was recently shown to correlate with better prognosis in Primary Sclerosing Cholangitis (PSC). We aimed at evaluating the impact of SAP improvement to below 1.5 the upper limit of normal (ULN) on the prognosis of this cholestatic liver disease.
  
  
  METHODS
  Oxford PSC database was screened for cases diagnosed between 1980 and 2004. Cases which met the inclusion criteria were retrospectively examined for clinical parameters, laboratory values, and clinical end points (liver decompensation, liver transplantation, and liver-related deaths including cholangiocarcinoma). Cases were followed-up to 31/12/2010.
  
  
  RESULTS
  139 patients were included, (87 males). Improvement of SAP to below 1.5 ULN was achieved by 55 (40%) patients in a median time of 2 years, compared to 84 (60%) who did not. 3/55 (6%) patients with SAP improvement reached an end point compared to 32/84 (38%) patients with no SAP improvement (p <0.0001). 13/84 (15%) patients with no SAP improvement developed cholangiocarcinoma compared to no cholangiocarcinoma in the group with SAP improvement (p = 0.002). The end point free survival was significantly longer in patients with SAP improvement (p <0.0001). The significance of SAP improvement as a predictor of prognosis persisted after controlling for other clinical and laboratory variables. Improvement of SAP to below 1.5 ULN was comparable to complete normalization of SAP in terms of prognosis.
  
  
  CONCLUSIONS
  Improvement in SAP to below 1.5 ULN is associated with better outcome and reduced risk of CCA in PSC. This was comparable to the achievement of complete normalization of SAP.
authors.affiliation: Transitional Gastroenterology Unit, Oxford University Hospitals, Oxford, United Kingdom. saidalmammari@hotmail.com
authors.forename: Said
authors.initials: S
authors.lastname: Al Mamari
authors.forename: Jelena
authors.initials: J
authors.lastname: Djordjevic
authors.forename: John S
authors.initials: JS
authors.lastname: Halliday
authors.forename: Roger W
authors.initials: RW
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood*; D001650:Bile Duct Neoplasms / Q000453:epidemiology*; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000097:blood; D018281:Cholangiocarcinoma / Q000453:epidemiology*; D015209:Cholangitis, Sclerosing / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase