title: A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).
abstract: BACKGROUND
  Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH.
  
  
  METHODS
  The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen).
  
  
  RESULTS
  Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis.
  
  
  CONCLUSIONS
  Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.
authors.affiliation: Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA. zobair.younossi@inova.org
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jarrar
authors.forename: Clare
authors.initials: C
authors.lastname: Nugent
authors.forename: Manpreet
authors.initials: M
authors.lastname: Randhawa
authors.forename: Mariam
authors.initials: M
authors.lastname: Afendy
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
authors.forename: Nila
authors.initials: N
authors.lastname: Rafiq
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.forename: Vikas
authors.initials: V
authors.lastname: Chandhoke
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
mesh_terms: D054392:Adipokines / Q000097:blood; D052242:Adiponectin / Q000097:blood; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D005260:Female; D006706:Homeostasis; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000473:pathology; D052243:Resistin / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; D015415:Biomarkers; D016207:Cytokines; D053538:Keratin-18; D052243:Resistin