Novel Serum Biomarker Candidates for Liver Fibrosis in Hepatitis C Patients

Abstract

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

Relationship analysis between gene expression profiles and rat liver cirrhosis occurrence

“…Among the genes participating in inflammation, A2M was always used as a biological indicator to assess hepatic fibrosis and cirrhosis, and was found to be up-regulated at 3 weeks in this study. Gangadharan et al (2007) pointed out that the expression of A2M was strengthened with the development of hepatic fibrosis, which was consistent with the current study result. Wald et al (2004) found that up-regulation of CXCL12 in liver during chronic HCV and HBV infection may support the establishment of a chronic inflammatory state and a progressive fibrotic process, thus the down-regulation of CXCL12 at 6 and 9 weeks lead to inflammation response inhibition, as shown in Figure 5A and indicated an accordingly result.…”

Zinc α2-Glycoprotein: A Multidisciplinary Protein

“…Although the exact mechanism by which ZAG actively participates in tumor proliferation is not known, a large body of data exists in favor of the expression of ZAG with respect to the stages of tumor (39)(40)(41)(42). ZAG is designated as a potential biomarker of different types of carcinomas (6,7,27,35,38,(43)(44)(45)(46).…”

Investigation of Plasma Biomarkers in HIV-1/HCV Mono- and Coinfected Individuals by Multiplex iTRAQ Quantitative Proteomics

“…This protein was also differentially expressed between HIV-1-resistant women and control groups and downregulated by threefold in cervical mucosa of HIV-1-resistant women (Burgener et al, 2008). Gangadharan et al (2007) showed that both C3 and TTR were downregulated in the sera of hepatitis C patients with liver fibrosis.…”