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慢性乙型肝炎（Chronic hepatitis B, CHB）是全球肝细胞癌（Hepatocellular carcinoma, HCC）的主要病因。随着核苷（酸）类似物（Nucleos(t)ide analogues, NAs）和干扰素（Interferon, IFN）治疗的进步，越来越多患者可实现乙型肝炎病毒DNA(Hepatitis B virus DNA, HBV DNA)抑制，甚至乙型肝炎病毒表面抗原（Hepatitis B virus surface antigen,HBsAg）清除。本文所称“临床治愈（亦称功能性治愈）”以HBsAg清除为核心，停药后随访一定时间（如≥12个月）持续阴性为宜，并与仅病毒学抑制（HBV DNA阴性但HBsAg仍阳性）相区分。需要强调的是，临床治愈并不等同于HCC风险消失。既往肝硬化、高龄、男性、HBV基因型C及家族史等因素仍驱动治愈后的残余风险。NAs通过稳定抑制病毒复制可降低约50%的HCC风险，但诱导HBsAg清除的能力有限。IFN在抑制HBV编码的X蛋白（Hepatitis B virus X protein, HBx）的致癌活性、改善免疫微环境及促进HBsAg下降方面更具优势。近年来，IFN与NAs、RNA干扰药物，主要是小干扰RNA(Small interfering RNA, siRNA)或反义寡核苷酸（Antisense oligonucleotide, ASO）等联合方案显著提高临床治愈率，被认为是降低长期HCC风险最具潜力的策略。未来需建立治愈后特异的风险分层与随访路径，实现从“控病毒”向“持续防癌”的管理转变。
Abstract：Chronic hepatitis B(CHB) remains a major global cause of hepatocellular carcinoma(HCC). With advances in nucleos(t)ide analogue( NA) and interferon( IFN) therapies, an increasing proportion of patients can achieve sustained hepatitis B virus DNA(HBV DNA) suppression and even hepatitis B surface antigen(HBs Ag) clearance. In this review, clinical cure(also referred to as functional cure) is defined by HBs Ag seroclearance, ideally sustained for at least 12 months after treatment cessation, and is distinguished from virological suppression characterized by undetectable HBV DNA with persistent HBs Ag positivity. Importantly, clinical cure does not eliminate the risk of HCC. Residual risk remains and is influenced by factors including prior cirrhosis, advanced age, male sex, HBV genotype C, and a family history of HCC. NAs reduce HCC incidence by approximately 50% through durable suppression of viral replication but have limited capacity to induce HBs Ag clearance. In contrast, IFN exerts additional benefits by inhibiting the oncogenic activity of hepatitis B virus X protein( HBx), modulating the immune microenvironment, and promoting HBs Ag decline. Recent advances in combination therapies, including IFN with NAs or RNA interference – based agents—particularly small interfering RNA( si RNA) and antisense oligonucleotides( ASOs)—have markedly improved clinical cure rates and are considered among the most promising strategies for reducing long-term HCC risk. Future efforts should focus on establishing post-cure risk stratification and surveillance strategies to enable a transition in disease management from“ viral suppression” to“ sustained cancer prevention”.
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基本信息:
中图分类号:R512.62;R735.7
引用信息:
[1]高子轩,郝红晓,姚林梅,等.慢性乙型肝炎临床治愈后的肝癌发生风险[J].病毒学报().
基金信息:
国家重点研发计划“重要病毒性肝炎病原特征与肝炎病毒复制机理研究”（项目号：2023YFC2306900）,题目：原因不明和新发突发肝炎的监测、病原筛查及诊断体;国家重点研发计划（项目号：2023YFC2308105）,题目：成人慢乙肝抗病毒治疗联合新型免疫治疗的临床研究; 北京市卫健委高层次公共卫生、技术人才建设项目（项目号：学科带头人-03-26）,题目：高层次公共卫生技术人才建设项目培养计划; 北京市医院管理中心“登峰”人才培养计划（项目号：DFL20241803）,题目：北京市医院管理中心“登峰”人才培养计划
2026-05-29
2026-05-29
2026-05-29