Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8⁺ T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver — and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis — profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection.

乙型肝炎病毒 (HBV) 是一种非细胞病变性嗜肝病毒，有可能引起持续感染，最终导致肝硬化和肝细胞癌。在过去的四十年里，HBV 基因表达和复制的基本原理以及控制感染结果的病毒和宿主决定因素已在很大程度上得到揭示。尽管 HBV 似乎很少或不会诱导先天免疫激活，但适应性免疫反应介导病毒清除和肝脏疾病。在这里，我们回顾了我们目前对 HBV 感染的免疫生物学和发病机制的了解，特别关注 CD8 ^+的作用T 细胞以及最近几项挑战当前教条的突破。例如，我们现在相信 HBV 整合到宿主基因组中通常作为慢性感染期间乙型肝炎表面抗原 (HBsAg) 表达的相关来源，可能引发功能失调的 T 细胞反应并有利于有害的免疫病理学。此外，肝脏独特的血液动力学和解剖结构——以及它们在疾病进展为肝纤维化和肝硬化期间经常经历的变化——深刻影响了 T 细胞的启动、分化和功能。我们还讨论了为什么限制由 HBV 特异性 T 细胞触发的肝内炎症过程的治疗方法可能对慢性感染患者出人意料地有益。