title: Biomarkers of Hepatic Fibrosis in Chronic Hepatitis C: A Comparison of 10 Biomarkers Using 2 Different Assays for Hyaluronic Acid.
abstract: BACKGROUND
  Advancing fibrosis is regarded as the most important factor when stratifying patients with chronic hepatitis C for retreatment.
  
  
  OBJECTIVE
  (1) To compare the performance of 10 biomarkers of fibrosis, including patented tests, among patients with chronic hepatitis C and treatment failure; and (2) to assess the impact on biomarker performance of using 2 different assays of hyaluronic acid (HA).
  
  
  METHODS
  For 80 patients, liver histology (Metavir) was compared with biomarker scores using sera obtained within 6 months of liver biopsy (indirect biomarkers: AST:ALT ratio, APRI, Forns index, FIB-4, Fibrometer V3G; direct biomarkers: ELF, Fibrospect II, Hyaluronic acid-HA, Fibrometer V2G, Hepascore). Direct biomarker scores were calculated using 2 validated assays for HA (ELISA and radiometric).
  
  
  RESULTS
  Using the ELISA assay for HA to calculate the direct panels, all 10 of the biomarkers exhibited comparable overall discriminatory performance (unweighted Obuchowski measure, ordROC 0.92-0.94, P-value>0.05) except AST:ALT ratio and APRI (ordROC 0.86-0.88, P-value<0.05). For the detection of moderate (F2-4) and advanced (F3-4) fibrosis, the AUROC of Fibrometer 2G were significantly higher than AST:ALT ratio and APRI but none of the other biomarkers. Good correlation was observed between the 2 HA assays (intraclass correlation coefficient=0.873) with the ELISA assay exhibiting superior diagnostic performance (ordROC 0.92 vs. 0.88, P-value=0.003). Importantly, the performance of many of the direct biomarkers at their diagnostic thresholds was heavily influenced by the choice of HA assay.
  
  
  CONCLUSIONS
  Although many biomarkers exhibited good diagnostic performance for the detection of advancing fibrosis, our results indicate that diagnostic performance may be significantly affected by the selection of individual component assays.
authors.affiliation: *Institute for Liver & Digestive Health, University College London ‡Department of Clinical Microbiology and Virology, University College London Hospitals NHS Foundation Trust, London †Public Health Sciences and Medical Statistics, University of Southampton, Southampton, UK §Department of Medicine 1, University of Erlangen, Erlangen ¶Institute of Molecular and Translational Medicine #Department of Medicine **Research Center for Immunology (FZI), University of Mainz, Mainz, Germany ∥Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, 5020 Salzburg, Austria ††Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Tanwar
authors.forename: Paul M
authors.initials: PM
authors.lastname: Trembling
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Hogan
authors.forename: Julie
authors.initials: J
authors.lastname: Parkes
authors.forename: Scott
authors.initials: S
authors.lastname: Harris
authors.forename: Paul
authors.initials: P
authors.lastname: Grant
authors.forename: Eleni
authors.initials: E
authors.lastname: Nastouli
authors.forename: Mathias
authors.initials: M
authors.lastname: Ocker
authors.forename: Klaus
authors.initials: K
authors.lastname: Wehr
authors.forename: Christoph
authors.initials: C
authors.lastname: Herold
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: William M
authors.initials: WM
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006820:Hyaluronic Acid