title: Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients.
abstract: OBJECTIVE
  In chronic hepatitis C (CHC) infection, a liver biopsy provides important information that guides treatment decisions, but is invasive, expensive and associated with possible complications. Extracellular matrix remodeling proteins may be useful non-invasive markers of fibrosis. The aim of this study was to evaluate the diagnostic accuracy of a panel of these markers in CHC patients, develop a predictive algorithm that differentiates no/mild (METAVIR F0-F1) from moderate/severe (F2-F4) fibrosis, and validate the model in external cohorts.
  
  
  METHODS
  A combination of matrix markers were initially evaluated and optimized in 294 CHC patients from a single center, and validated in an external cohort of 402 patients.
  
  
  RESULTS
  Hyaluronic acid, TIMP-1 and alpha2-macroglobulin were selected as having the best predictive accuracy for F2-F4 fibrosis (combined AUROC = 0.831). At an index cut-off >0.36 and prevalence for F2-F4 of 52%, results in all 696 patients indicated positive and negative predictive values of 74.3 and 75.8% with an accuracy of 75%.
  
  
  CONCLUSIONS
  The three-marker panel may reliably differentiate CHC patients with moderate/severe fibrosis from those with no/mild fibrosis, although accurate delineation between stages was not possible. Prospective studies are required to determine the potential utility of the marker panel in guiding treatment decisions and following disease progression.
authors.affiliation: Duke Clinical Research Institute and Division of Gastroenterology, Duke University Medical Center, P.O. Box 17969, Durham, NC 27715, USA.
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobson
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Esther
authors.initials: E
authors.lastname: Oh
authors.forename: Katie M
authors.initials: KM
authors.lastname: Smith
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012698:Serologic Tests; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D000511:alpha-Macroglobulins; D006820:Hyaluronic Acid