Exploring the role of hepatitis B virus infection in the origins of human liver cancer

Abstract

Hepatitis B virus (HBV) infection is a major risk factor for chronic liver disease and human hepatocellular carcinoma. However, the precise role of HBV in liver cancer initiation and progression remains elusive, and so does the effect of viral integration. In this doctoral thesis, we applied various sequencing strategies, including short- and long-read approaches, to decipher the mutational landscape of different HBV-infected samples. We demonstrated that HBV integrations can mediate complex rearrangements and are already present in the early stages of chronic liver disease. Additionally, we discovered that the infected cirrhotic liver is molecularly diverse, with regenerative nodules functioning as nearly isolated units where different clones coexist and accumulate mutations driven by specific mutational processes.