Role of Immune Cells in Hepatitis B Virus and Associated Sequelae

Hepatitis B virus (HBV) chronically infects 250 million people worldwide, making it a primary risk factor for progressive liver disease. The virus itself is not responsible for liver damage. HBV can replicate at very high levels and produces large amounts of viral antigen, but this does not lead to hepatocyte death or liver inflammation. Instead, pathogenesis of chronic hepatitis B (CHB) is driven by the interaction between the host immune system and the virus. In chronically infected individuals, the HBV-specific immune response is dysfunctional and not able to clear the infection. This inability to clear the virus leads to aberrant immune activation in the liver, causing hepatocellular damage that, over time, leads to fibrosis, cirrhosis, and liver cancer. This review covers two aspects of sequalae associated with CHB: (a) mechanisms of tissue damage leading to fibrosis and (b) dysfunctional features of HBV-specific immunity.