title: An apoptosis panel for nonalcoholic steatohepatitis diagnosis.
abstract: OBJECTIVE
  The extrinsic death receptor-mediated pathway of apoptosis is involved in nonalcoholic steatohepatitis (NASH) development. Our aims were to create and validate a noninvasive prediction model for NASH diagnosis based on specific circulating markers of apoptosis.
  
  
  METHODS
  Our initial cohort consisted of 95 consecutive patients undergoing a liver biopsy for clinically suspected NASH. Blood was obtained from each patient at the time of liver biopsy. Plasma caspase 3 generated cytokeratin-18 fragments (CK-18), soluble Fas (sFas), and soluble Fas ligand (sFasL) were measured. Histology was assessed by an experienced hepatopathologist. The validation cohort consisted of 82 consecutive patients that underwent liver biopsy at the time of bariatric surgery.
  
  
  RESULTS
  Patients with NASH had significantly higher levels of CK-18 and sFas than patients in the "not NASH" group [median (25th, 75th percentile): 508 (280, 846) U/L versus 176 (131, 224) U/L (p<0.001), and 11.8 (7.8, 12.5) ng/ml versus 5.9 (4.8, 8.3) ng/ml (p<0.001), respectively]. A significant positive correlation was revealed between the apoptosis markers and liver histopathology independent of other metabolic factors. A prediction model was generated including CK-18 fragments and sFas levels that showed an AUC of 0.93 and 0.79 in the initial and validation cohorts, respectively. A cutoff value using this model predicted NASH with a sensitivity and specificity of 88% and 89%, respectively.
  
  
  CONCLUSIONS
  Quantification of circulating levels of two apoptotic markers accurately predicts the presence of NASH, supporting the potential usefulness of these markers in clinical practice for noninvasive diagnosis of NASH.
authors.affiliation: Digestive Disease Institute, Sioux Falls, SD, USA.
authors.forename: Tarek I Abu-Rajab
authors.initials: TI
authors.lastname: Tamimi
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Elgouhari
authors.forename: Naim
authors.initials: N
authors.lastname: Alkhouri
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Yerian
authors.forename: Michael P
authors.initials: MP
authors.lastname: Berk
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Schauer
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Zein
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D053222:Fas Ligand Protein / Q000097:blood; D005234:Fatty Liver / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
chemical_list: D015415:Biomarkers; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053538:Keratin-18; D010446:Peptide Fragments; D019014:fas Receptor