Discovery of new liver fibrosis markers in hepatitis C patients using proteomics

Journal article

Introduction: 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.

Aim: The objective of this study was to use proteomics to identify novel fibrosis biomarkers in hepatitis C patients with different degrees of liver fibrosis.

Method: 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 visualising the separated proteins we were able to identify proteins which were increasing or decreasing in hepatic cirrhosis. Identified markers were validated across all Ishak stages and compared to the markers used in FibroTest, Enhanced Liver Fibrosis (ELF) test, Hepascore and FIBROSpect by western blotting.

Results: 44 candidate biomarkers for hepatic fibrosis were identified of which 20 were novel. 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 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.

Conclusion: This study identifies 20 novel fibrosis biomarker candidates. The proteins identified by these improved approaches may help to assess hepatic fibrosis and eliminate the need for invasive liver biopsies.

Authors: Gangadharan, B; Bapat, M; Rossa, J; Antrobus, R; Chittenden, D

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BMJ Publishing Group
• Journal: Gut
• Volume: 60
• Issue: Supplement 2
• Article number: A56
• Publication date: 2011-09-06
• Acceptance date: 2011-09-01
• DOI: 10.1136/gutjnl-2011-300857b.15
• ISSN: 1468-3288, 0017-5749