Received on March 19, 2007
Accepted on July 24, 2007

Proteomics and Protein Markers

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

¹ Oxford Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom

^* To whom correspondence should be addressed. E-mail: Bevin.Gangadharan{at}bioch.ox.ac.uk.

Background: Liver biopsy is currently the gold standard for assessing liver fibrosis, and no reliable noninvasive diagnostic approach is available. Therefore a suitable serologic biomarker of liver fibrosis is urgently needed.

Methods: We used a proteomics method based on 2-dimensional gel electrophoresis to identify potential fibrosis biomarkers. Serum samples from patients with varying degrees of hepatic scarring induced by infection with the hepatitis C virus (HCV) were analyzed and compared with serum from healthy controls.

Results: We observed the most prominent differences when we compared serum samples from cirrhotic patients with healthy control serum. Inter--trypsin inhibitor heavy chain H4 (ITIH4) fragments, 1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and 2 glycoprotein I (2GPI) were increased. In general, 2 macroglobulin (a2M) and immunoglobulin components increased with hepatic fibrosis, whereas haptoglobin and complement components (C3, C4, and factor H-related protein 1) decreased. Novel proteins associated with HCV-induced fibrosis included ITIH4 fragments, complement factor H-related protein 1, CD5L, Apo L1, 2GPI, and thioester-cleaved products of a2M.

Conclusions: Assessment of hepatic scarring may be performed with a combination of these novel fibrosis biomarkers, thus eliminating the need for liver biopsy. Further evaluation of these candidate markers needs to be performed in larger patient populations. Diagnosis of fibrosis during early stages will allow early treatment, thereby preventing fibrosis progression.