title: Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.
abstract: Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis.
  
  
  METHODS
  This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses.
  
  
  RESULTS
  Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival.
  
  
  CONCLUSIONS
  Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.
authors: Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Moira
authors: M
authors: Hilscher
authors: Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN, USA.
authors: Felicity B
authors: FB
authors: Enders
authors: Division of Gastroenterology & Hepatology, Mayo Clinic, Scottsdale, AZ, USA.
authors: Elizabeth J
authors: EJ
authors: Carey
authors: Executive Vice Provost & Dean, College of Health Solutions, Arizona State University, Phoenix, AZ, USA; Division of Gastroenterology & Hepatology. Mayo Clinic, Scottsdale, AZ.
authors: Keith D
authors: KD
authors: Lindor
authors: Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA.
authors: James H
authors: JH
authors: Tabibian
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood*; D001650:Bile Duct Neoplasms / Q000453:epidemiology; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D018281:Cholangiocarcinoma / Q000453:epidemiology; D015209:Cholangitis, Sclerosing / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D001663:Bilirubin