TRR179 – Determinants and dynamics of elimination versus persistence of hepatitis virus infection

Infections with the most prevalent hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) have a major impact on human health. They are amongst the most widespread viral infections of humans worldwide, with a high propensity to establish persistence. Importantly, patients with chronic viral hepatitis are at high risk to develop severe if not terminal liver disease, including liver fibrosis, liver cirrhosis and hepatocellular carcinoma. This risk is exacerbated in case of HBV - hepatitis D virus (HDV) or HBV - HCV co-infections. HDV infection is attracting increasing research interest. Moreover, recent years have seen renewed interest in hepatitis A virus (HAV) infection that never establishes chronicity, yet has a very protracted course of infection. The outcome of hepatitis virus infections, either acute self-limiting or persistent is a dynamic process that is governed by the complex interplay of multiple host and viral parameters. These include an insufficient antiviral immune response, the tolerogenic liver microenvironment and viral factors that depend on the individual infecting pathogen. So far, research mainly focussed on identifying single molecules or pathways or observing isolated biological events by using steady-state analyses. However, understanding the molecular mechanisms determining elimination versus persistence of virus infection requires an integrative approach that must account for the complex and dynamic interplay of the various immune cells involved in antiviral defence, the viral factors, the immune-privileged liver microenvironment and its alterations induced by viral infection and immune responses.