Assessment of hepatitis B virus intra-host population and host-specific immune marker diversity with nextgeneration sequencing: from chronic infection to endstage liver disease and liver cancer.

Hepatitis B virus (HBV) targets the liver and infection with HBV gradually leads to end stage liver diseases like liver cancer (Hepatocellular carcinoma) with annually almost 500,000 deaths. Actually, chronically infected HBV patients, have a high risk to develop above-mentioned liver complications. Viruses like other biological organisms change over time (evolution). These alterations at the viral genome are named mutations. Mutations have an impact on the pathogenesis of these viruses and can subsequently show different clinical outcomes. The complexity of viral infection is the result of interactions between viral pathogenesis and the host immune system. It can be a great step in diagnosis and therapy if we find particular mutations in the HBV genome as risk prediction and understand their association with patients’ immune-genetic parameters. In this project proposal, we aim at identifying specific mutations in the HBV genome that can be relevant for the prediction of severe stages of illness and genetic diversity of human immunogenetic parameters. We have an archive of serial serum samples of HBV chronic carriers, from the original diagnosis date until present date. Our study groups consist of 82 HBV patients who developed liver cancer gradually and 192 HBV infected cases that are still in a chronic carrier status. We will isolate and sequence the HBV genome in both groups and identify and compare the variations at the level of the genome with clinical manifestations in both groups. Results of this project will open new horizons in the diagnosis and treatment of end stage liver disease.