Novel serum biomarker candidates for liver fibrosis in hepatitis C patients.
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-alpha-trypsin inhibitor heavy chain H4 (ITIH4) fragments, alpha1 antichymotrypsin, apolipoprotein L1 (Apo L1), prealbumin, albumin, paraoxonase/arylesterase 1, and zinc-alpha2-glycoprotein were decreased in cirrhotic serum, whereas CD5 antigen-like protein (CD5L) and beta2 glycoprotein I (beta2GPI) were increased. In general, alpha2 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, beta2GPI, 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.
Gangadharan
Bevin
B
Oxford Antiviral Drug Discovery Unit, Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom. Bevin.Gangadharan@bioch.ox.ac.uk
Antrobus
Robin
R
Dwek
Raymond A
RA
Zitzmann
Nicole
N
D015415:Biomarkers / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis*
D015415:Biomarkers; D020543:Proteome