title: Discovery of novel biomarker candidates for liver fibrosis in hepatitis C patients: a preliminary study.
abstract: BACKGROUND
  Liver biopsy is the reference standard for assessing liver fibrosis and no reliable non-invasive diagnostic approach is available to discriminate between the intermediate stages of fibrosis. Therefore suitable serological biomarkers of liver fibrosis are urgently needed. We used proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.
  
  
  RESULTS
  Proteins in plasma samples from healthy control individuals and patients with hepatitis C virus (HCV) induced cirrhosis were analysed using a proteomics technique: two dimensional gel electrophoresis (2-DE). This technique separated the proteins in plasma samples of control and cirrhotic patients and by visualizing the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak fibrosis stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by Western blotting. Forty four candidate biomarkers for hepatic fibrosis were identified of which 20 were novel biomarkers of liver fibrosis. Western blot validation of all candidate markers using plasma samples from patients across all Ishak fibrosis scores showed that the markers which changed with increasing fibrosis most consistently included lipid transfer inhibitor protein, complement C3d, corticosteroid-binding globulin, apolipoprotein J and apolipoprotein L1. These five novel fibrosis markers which are secreted in blood showed a promising consistent change with increasing fibrosis stage when compared to the markers used for the FibroTest, ELF test, Hepascore and FIBROSpect. These markers will be further validated using a large clinical cohort.
  
  
  CONCLUSIONS
  This study identifies 20 novel fibrosis biomarker candidates. The proteins identified may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.
authors: Oxford Antiviral Drug Discovery Unit, Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford, United Kingdom. Bevin.Gangadharan@bioch.ox.ac.uk
authors: Bevin
authors: B
authors: Gangadharan
authors: Manisha
authors: M
authors: Bapat
authors: Jan
authors: J
authors: Rossa
authors: Robin
authors: R
authors: Antrobus
authors: David
authors: D
authors: Chittenden
authors: Bettina
authors: B
authors: Kampa
authors: Eleanor
authors: E
authors: Barnes
authors: Paul
authors: P
authors: Klenerman
authors: Raymond A
authors: RA
authors: Dwek
authors: Nicole
authors: N
authors: Zitzmann
mesh_terms: D000328:Adult; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D051152:Clusterin / Q000097:blood; D015933:Complement C3d / Q000378:metabolism; D005260:Female; D006526:Hepatitis C / Q000097:blood* / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014156:Transcortin / Q000378:metabolism
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D015415:Biomarkers; D051152:Clusterin; D008075:Lipoproteins, HDL; C036321:apolipoprotein F; D015933:Complement C3d; D014156:Transcortin