Single-cell atlas reveals characteristic changes in intrahepatic HBV-specific leukocytes

Hepatitis B virus (HBV)-specific CD8⁺ T cells play a central role in the clearance of virus and HBV-related liver injury. Acute infection with HBV induces a vigorous, multifunctional CD8⁺ T cell response, whereas chronic one exhibits a weaker response. Our study elucidated HBV-specific T cell responses in terms of viral abundance rather than the timing of infection. We showed that in the premalignant stage, the degree of impaired T cell function was not synchronized with the viral surface antigen, which was attributed the liver's tolerance to the virus. However, after the development of hepatocellular carcinoma, T cell exhaustion was inevitable, and it was marked by the exhaustion of the signature transcription factor TOX.