Biomarker discovery for hepatitis C virus infection
Hepatitis C is a major public health problem with high incidence in regions such as Egypt and other Mediterranean countries. Chronically infected individuals are at risk of developing cirrhosis, hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma. Unlike other chronic infections such as HIV, clearance of HCV is possible. Such clearance may occur spontaneously during the acute phase of infection or in response to therapeutic administration of type I interferon (IFN). A greater understanding of this phenomenon could help design prophylactic HCV vaccines to boost immune activity. The EU-funded Sphinx initiative wishes to identify novel biomarkers, and provide new insight into the mechanisms of spontaneous clearance of HCV during acute infection. Project partners plan to use omics technologies to characterise the HCV-specific cellular immune response during the clearance phase, and assess any genetic and epigenetic variations that could potentially predict viral clearance. A prime objective of the Sphinx initiative is the recruitment of a HCV patient cohort and the establishment of a central database with clinical, epidemiological and biological data for all patients. Protein signatures have been obtained for patients with hepatitis A, B or C infection and are currently being validated as disease biomarkers. In order to analyse the immune cell activation during spontaneous clearance of HCV, scientists are performing database and in silico search. This has led to the identification of T cell epitopes specific for HCV genotype 4, as well as epitopes shared among different virus genotypes. Additionally, the consortium is interested in performing a genetic analysis of polymorphisms in various genes in order to identify potential correlations with spontaneous resolution of HCV. A total of 43 genes have been selected with particular emphasis on the IL28B gene. The support of scientific exchanges between partners has provided training opportunities in clinical epidemiology and biomarker discovery. Coupled with the developed assays, Sphinx project outcomes have the potential to improve and speed up identification of patients presenting with acute HCV. Furthermore, new knowledge about acute HCV disease pathogenesis will lead to better disease management and prompt therapeutic intervention for those who require it.
