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This Article Full Text Full Text (PDF) 089144.Supplemental Data All Versions of this Article: clinchem.2007.089144v1 53/10/1792    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Gangadharan, B. Articles by Zitzmann, N. Search for Related Content PubMed PubMed Citation Articles by Gangadharan, B. Articles by Zitzmann, N. Related Collections Proteomics and Protein Markers

Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

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

^aAddress correspondence to this author at: Oxford Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Rd., Oxford, OX1 3QU, United Kingdom. Fax 44-1865-275716; 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 ß2 glycoprotein I (ß2GPI) 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, ß2GPI, 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.

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