How does hepatitis B cause liver damage, and how is it linked to hepatocellular carcinoma?

HBV is not directly cytopathic; damage is from the host cytotoxic T-cell immune response against infected hepatocytes. The risk of hepatocellular carcinoma relates to HBV DNA level (the REVEAL study) and to viral DNA integration and X-protein inactivation of p53.

Clinical relevance. Understanding immune-mediated damage and the HBV DNA-HCC link justifies viral suppression and ongoing HCC surveillance.

More Detail

Pathogenesis of hepatitis B and HCC

Liver injury in HBV is immune-mediated, and the virus is oncogenic through several mechanisms.

Immune-mediated damage

• HBV itself is not directly cytopathic.
• HBV-specific cytotoxic CD8 T cells recognise viral antigen on infected hepatocytes (via HLA class I) and cause the damage.
• The balance of immune response determines outcome: a strong response clears the virus; a poor response leads to persistence and chronic infection.

Link to hepatocellular carcinoma

• The REVEAL study showed HCC risk relates to the level of HBV DNA rather than the ALT level.
• Integration of viral DNA into the host genome and X-protein inactivation of p53-induced apoptosis promote carcinogenesis.
• HCC can develop even in late integrated-phase disease, so surveillance continues even when HBV DNA is negative.