title: Cytokeratin 18 fragment levels as a noninvasive biomarker for nonalcoholic steatohepatitis in bariatric surgery patients.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) is extremely common among morbidly obese patients. We assessed the usefulness of plasma caspase-generated cytokeratin 18 (CK-18) fragments as a novel marker for NAFLD in a bariatric cohort.
  
  
  METHODS
  The cohort consisted of 99 consecutive patients who underwent liver biopsy at the time of bariatric surgery. CK-18 levels were measured by using an enzyme-linked immunosorbent assay before and 6 months after surgery. Patients were subdivided into 4 histologic groups: not NAFLD (normal liver biopsy), nonalcoholic fatty liver (NAFL), borderline diagnosis, and definitive nonalcoholic steatohepatitis (NASH).
  
  
  RESULTS
  CK-18 levels were significantly higher in subjects with NASH compared with those with not NAFLD, NAFL, or borderline diagnosis (median [25th quartile, 75th quartile], 389 U/L [275, 839] vs 196 U/L [158, 245], vs 217 U/L [154, 228], or vs 200 U/L [176, 274], respectively; P < .0001). CK-18 levels were significantly higher in subjects with moderate to severe fibrosis versus those with no or mild fibrosis (334.5 U/L [240.5, 896] vs 207 U/L [175, 275], respectively; P = .007). A significant decrease in CK-18 levels was observed in most patients 6 months postoperatively. The area under the receiver operating characteristic curve for NASH diagnosis was estimated to be 0.88 (95% confidence interval, 0.77-0.99). The values with the best combination of sensitivity and specificity were 252 U/L (sensitivity, 82%; specificity, 77%) and 275 U/L (sensitivity, 77%; specificity, 100%).
  
  
  CONCLUSIONS
  These results support the potential utility of this test for diagnosis and staging of NAFLD before bariatric surgery.
authors.affiliation: Department of Endocrinology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Dima L
authors.initials: DL
authors.lastname: Diab
authors.forename: Lisa
authors.initials: L
authors.lastname: Yerian
authors.forename: Philip
authors.initials: P
authors.lastname: Schauer
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Kashyap
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
mesh_terms: D000328:Adult; D050110:Bariatric Surgery; D015415:Biomarkers; D001706:Biopsy; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005234:Fatty Liver / Q000175:diagnosis*; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D053538:Keratin-18