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我国乙肝病毒携带者人数约7500万，乙肝病毒感染是引起终末期肝病的主要原因，是我国卫生健康方面主要负担之一。实现慢乙肝功能性治愈可有效避免相关肝病发生，延长患者的生存期，目前已成为乙肝领域研究热点。相当比例慢乙肝优势人群经干扰素治疗后可实现安全停药，然而，停药判断缺少简便、可靠、易操作的生物标志物。随着乙肝新药或新药联合治疗方案不断出现，越来越多患者有望实现功能性治愈，迫切需要解决慢乙肝功能性治愈的可靠生物标志物的问题。本文综述了基于乙型肝炎病毒本身的病毒学标志物（如乙肝两对半、HBV DNA/RNA、HBcrAg、HBV cccDNA），以及宿主相关免疫学生物标志物（如乙肝病毒特异性抗体、免疫细胞等）的发展历程与各评价指标的特色，并针对目前存在的问题，提出我们的观点与展望。
Abstract：Approximately 75 million individuals in China are carriers of the hepatitis B virus(HBV), which is the primary cause of end-stage liver disease and represents a major public health burden. Achieving a functional cure for chronic hepatitis B(CHB) can effectively prevent the progression of related liver diseases and extend patient survival. This has become a key area of research in the field of hepatitis B. A significant proportion of CHB patients can achieve a functional cure and safely discontinue therapy following interferon treatment.However, the lack of simple, reliable, and easily operable biomarkers to guide treatment cessation remains a critical challenge. With the continuous development of novel antiviral agents and combination therapies, an increasing number of patients are expected to achieve functional cure, highlighting the urgent need for reliable biomarkers to confirm this outcome. This review summarizes the development and the unique applications of virological biomarker based on the hepatitis B virus itself(such as hepatitis B serological markers, HBV DNA/RNA, HBcrAg, and HBV cccDNA), as well as host-related immunological biomarkers(including HBV-specific antibodies and immune cells). Finally, the current challenges are addressed, and future directions for research in this area are proposed.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250006
中图分类号:R512.62
引用信息:
[1]朱丽芬,周佩,蔡海奕等.慢性乙型肝炎功能性治愈生物标志物的过去、现状与未来[J].病毒学报,2025,41(02):279-290.DOI:10.13242/j.cnki.bingduxuebao.250006.
基金信息:
国家自然科学基金青年科学基金项目（项目号：3240080489）,题目：HBsAg特异性BCR在慢乙肝功能性治愈中的图谱特征与预测价值; 广东省重点领域研发计划（项目号：2022B1111020002）,题目：华南地区主要流行人类病毒模式小鼠资源库的建立及评估应用; 广东省区域联合基金-青年基金项目（项目号：2022A1515110483）,题目：干扰素a调控肝脏M1型巨噬细胞极化清除HBsAg机制研究; 广州市重点研发计划（项目号：202206080001）,题目：靶向宿主免疫和病毒cccDNA的慢性乙肝治愈的新机制新靶点新策略临床转化研究; 广州市科技计划（市院联合项目）（项目号：202201020374）,题目：广州市传染病动物模型重点实验室; 广州市校（院）企联合资助专题（项目号：2023A03J0786）,题目：HLA-I类HBV特异性CTL表位在慢乙肝抗病毒过程中的变化~~