Hepatitis B and C : pathogenesis and novel therapeutic approaches

In order to develop novel strategies for HBV-induced HCC prevention, it is crucial to understand what are the viral escape strategies in order to allow it to bypass antiviral and immune pressures. Studies on virus-cell interactions and characterization of the innate immune response of the hepatocyte against HBV should indeed contribute to identify mechanisms implicated in viral persistence and cell transformation. In addition, novel strategies for chronically infected patients immunization in conjunction with antiviral treatments are also under evaluation in the hope of invigorating specific T cell responses. In vitro research programs are aimed at dissecting HVB/Toll-like receptors interactions as well as their associated signalling pathways in order to strengthen hepatic innate immunity functions in a therapeutic prospective. Novel antiviral approachs are also being evaluated on wild-type and treatment-associated mutant strains in hepatocytic cell lines. Novel molecules and other therapeutic strategies (such as therapeutic vaccines) of chronic hepatitis B is being investigated at the preclinical stage thanks to several cellular and animal models that have been developed in the laboratory (these are Beijing duck infected with its endogenous virus DHBV, and american woodchuck infected with WHV).

HCV infection puts patients at higher risk for developing HCC, as is the case for HBV. This viral infection alters glucidic and lipid metabolic functions of the liver, at least in part to confer specific physicochemical properties to virions that could in turn foster viral persistence. In this context, our goal is to better comprehend these alterations at the cell and infectious virion level in experimental models and through clinical research studies. Targeted modulation of cell factors and pathways that we will identify as necessary for HCV particles production by the hepatocyte will allow the identification of targetable novel pathways but also the development of novel culture systems for this virus. Such advances will be of paramount importance for further understanding the infection and its role in HCC development.

Translational studies based on patients cohorts and other preclinical programs on the above mentioned themes are implemented jointly with the HCL (Lyon public hospitals network) in the context of the recent inauguration of a clinical research center.