Unit of Infectious Disease and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Liver Int. 2015 Jan;35 Suppl 1:121-8. doi: 10.1111/liv.12749.
Hepatitis B virus (HBV) infection acquired in adult life is generally self-limited while chronic persistence of the virus is the prevalent outcome when infection is acquired perinatally. Both control of infection and liver cell injury are strictly dependent upon protective immune responses, because hepatocyte damage is the price that the host must pay to get rid of intracellular virus. Resolution of acute hepatitis B is associated with functionally efficient, multispecific antiviral T-cell responses which are preceded by a poor induction of intracellular innate responses at the early stages of infection. Persistent control of infection is provided by long-lasting protective memory, which is probably sustained by continuous stimulation of the immune system by trace amounts of virus which are never totally eliminated, persisting in an occult episomic form in the nucleus of liver cells even after recovery from acute infection. Chronic virus persistence is instead characterized by a lack of protective T-cell memory maturation and by an exhaustion of HBV-specific T-cell responses. Persistent exposure of T cells to high antigen loads is a key determinant of functional T-cell impairment but also other mechanisms can contribute to T-cell inhibition, including the tolerogenic effect of the liver environment. The degree of T-cell impairment is variable and its severity is related to the level of virus replication and antigen load. The antiviral T-cell function is more efficient in patients who can control infection either partially, such as inactive HBsAg carriers with low levels of virus replication, or completely, such as patients who achieve HBsAg loss either spontaneously or after antiviral therapy. Thus, understanding the features of the immune responses associated with control of infection is needed for the successful design of novel immune modulatory therapies based on the reconstitution of efficient antiviral responses in chronic HBV patients.
乙型肝炎病毒（HBV）感染在成年时通常是自限性的，而当感染是在围生期获得时，病毒的慢性持续存在是常见的结果。感染的控制和肝细胞损伤都严格依赖于保护性免疫反应，因为肝细胞损伤是宿主必须付出的代价，以摆脱细胞内病毒。急性乙型肝炎的缓解与功能有效的、多特异性抗病毒 T 细胞反应有关，这些反应在前感染早期细胞内先天反应诱导不良的情况下发生。感染的持续控制由持久的保护性记忆提供，这可能是由持续刺激免疫系统的微量病毒维持的，这些病毒从未被完全消除，即使在急性感染后从恢复后，也以隐匿的附加体形式持续存在于肝细胞的核内。慢性病毒持续存在的特征是缺乏保护性 T 细胞记忆成熟和 HBV 特异性 T 细胞反应的衰竭。T 细胞持续暴露于高抗原负荷是功能 T 细胞损伤的关键决定因素，但其他机制也可以导致 T 细胞抑制，包括肝脏环境的耐受效应。T 细胞损伤的程度是可变的，其严重程度与病毒复制和抗原负荷水平有关。在能够部分控制感染的患者中，如病毒复制水平低的 HBsAg 携带者，或能够完全控制感染的患者，如自发或抗病毒治疗后 HBsAg 丢失的患者，抗病毒 T 细胞功能更为有效。因此，需要了解与感染控制相关的免疫反应的特征，以便成功设计基于慢性 HBV 患者中有效抗病毒反应重建的新型免疫调节疗法。
