title: Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of Biomarkers for Apoptosis but Not Necrosis.
abstract: OBJECTIVE
  Hepatocyte apoptosis or necrosis from accumulation of bile salts may play an important role in the disease progression of primary sclerosing cholangitis (PSC). The aim of the current study was to measure serum markers of hepatocyte apoptosis (cytokeratin-18 fragments--K18) and necrosis (high-mobility group protein B1--HMGB1) in adults with PSC and examine the relationship with disease severity.
  
  
  METHODS
  We measured serum levels of K18 and HMGB1 in well-phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was assessed biochemically, histologically, and PSC Mayo risk score. Quantification of hepatocyte apoptosis was performed using TUNEL assay.
  
  
  RESULTS
  The mean age of the study cohort was 49.7 ± 13.3 years and comprised of 67% men and 93% Caucasian. Serum K18 levels were significantly higher in the PSC patients compared to control (217.4 ± 78.1 vs. 157.0 ± 58.2 U/L, p = 0.001). However, HMGB1 levels were not different between the two groups (5.38 ± 2.99 vs. 6.28 ± 2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total bilirubin (r = 0.61, p ≤ 0.001), and albumin (r = -0.4, p = 0.02). Serum K18 levels also correlated with the level of apoptosis present on the liver biopsy (r = 0.8, p ≤ 0.001) and Mayo risk score (r = 0.4, p = 0.015).
  
  
  CONCLUSIONS
  Serum K18 but not HMGB1 levels were increased in PSC and associated with severity of underlying liver disease and the degree of hepatocyte apoptosis.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Masuoka
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Deppe
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Phelan
authors.initials: P
authors.lastname: Bybee
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Comerford
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Suthat
authors.initials: S
authors.lastname: Liangpunsakul
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghabril
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. nchalasa@iu.edu.|Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, USA. nchalasa@iu.edu.|David W. Crabb Professor of Medicine, 702 Rotary Building, Suite 225, Indianapolis, IN, 46202, USA. nchalasa@iu.edu.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000097:blood* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D053538:Keratin-18
keywords: Apoptosis; HMGB1; Hepatocyte necrosis; Serum K18; TUNEL; Ulcerative colitis