Shu Yiwen, Li Sumeng, Du Yanqin, Zheng Xin
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Institute of Infectious Diseases and Immunity, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2025 Jul 4;16:1611976. doi: 10.3389/fimmu.2025.1611976. eCollection 2025.
Despite the successful implementation of prophylactic vaccines, hepatitis B virus (HBV) continues to affect over 350 million individuals globally. It remains a predominant etiology of end-stage liver pathologies, including liver cirrhosis and hepatocellular carcinoma (HCC). While nucleos(t)ide analog (NUC) therapies effectively suppress viral replication, functional cure is achieved in less than 1% of patients annually. Given that viral clearance fundamentally requires reconstitution of antiviral immunity, emerging therapeutic paradigms necessitate combinatorial strategies integrating direct-acting antiviral agents with immunomodulatory interventions. Substantial research efforts have been directed toward elucidating the immunological mechanisms underlying HBV persistence during chronic infection. This review systematically summarizes the functional impairment of innate immune populations and unconventional T cell subsets across distinct clinical phases of chronic HBV infection, and characterizes longitudinal immune reconstitution patterns following antiviral treatments. Our review identifies potential immunological biomarkers and provides a mechanistic framework for developing targeted immunotherapies to achieve durable HBV control.
尽管预防性疫苗已成功实施，但乙型肝炎病毒（HBV）在全球范围内仍影响着超过3.5亿人。它仍然是终末期肝脏疾病（包括肝硬化和肝细胞癌（HCC））的主要病因。虽然核苷（酸）类似物（NUC）疗法可有效抑制病毒复制，但每年实现功能性治愈的患者不到1%。鉴于病毒清除从根本上需要重建抗病毒免疫力，新兴的治疗模式需要将直接作用抗病毒药物与免疫调节干预相结合的联合策略。大量研究工作致力于阐明慢性感染期间HBV持续存在的免疫机制。本综述系统总结了慢性HBV感染不同临床阶段先天免疫群体和非常规T细胞亚群的功能损害，并描述了抗病毒治疗后的纵向免疫重建模式。我们的综述确定了潜在的免疫生物标志物，并为开发靶向免疫疗法以实现持久的HBV控制提供了一个机制框架。
