乙型病毒性肝炎分子流行病学特征及特异性防控策略研究  

Molecular epidemiological characteristics and specific prophylactic and control strategy of hepatitis B

作　　者：陈一凡 曹广文 CHEN Yifan;CAO Guangwen(Department of Epidemiology,Second Military Medical University,Shanghai 200433,China;Key Laboratory of Biological Defense,Ministry of Education,Second Military Medical University,Shanghai 200433,China;Shanghai Key Laboratory of Medical Bioprotection,Second Military Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学流行病学教研室,上海200433 [2]生物安全防御教育部重点实验室,上海200433 [3]上海市医学生物防护重点实验室,上海200433

出　　处：《中华疾病控制杂志》2025年第2期125-131,248,共8页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(82473715);上海市公共卫生三年行动计划(GWV-10.1-XK17)。

摘　　要：目前,全球有2.57亿乙型病毒性肝炎(简称乙肝)病毒(hepatitis B virus,HBV)感染者,中国内地地区约有7500万HBV感染者,>30岁人群HBV感染率为7.54%。HBV感染在中国,农村地区高于城市,中部和南部地区感染率最高。HBV在全球有10个基因型,中国以B和C基因型为主。B型易在年轻人群横向传播,造成急性乙肝;C型易在家庭内传播,导致肝硬化和肝细胞癌(hepatocellular carcinoma,HCC)。乙肝疫苗可有效预防HBV慢性感染、肝硬化和HCC。HBV慢性感染约占中国HCC病因的84.4%。HBV通过病毒复制、变异和基因组整合发挥促癌作用。HBV的复制激活并维持了炎症微环境,后者诱导并选择了体细胞变异和病毒变异。与野生型HBV相比,变异型促癌能力更强,主要通过激活关键信号通路促使炎症微环境中的变异细胞逆向分化;HBV整合失活肿瘤抑制基因,激活端粒酶逆转录酶使肝细胞具有选择性生长优势。HCC高危HBV变异能够预测HCC发生、预后以及抗病毒的预防效果。抗病毒治疗降低了HCC的发生和术后复发,特别是通过抑制HBV核心启动子区变异发挥促癌作用,实现对HBV相关HCC的特异性防控。Currently,there are approximately 257 million individuals globally infected with hepatitis B virus(HBV).In China's mainland,about 75 million residents are chronically infected with HBV.Furthermore,the infection rate of HBV is 7.54%among those aged over 30 years.The prevalence of HBV infection is higher in rural areas than in urban areas.The highest rate of HBV infection is evident in the central and southern China.HBV has 10 genotypes,among which genotype B and C are endemic in China.Genotype B HBV is more apt to transmit horizontally in the young and cause acute hepatitis B,whereas genotype C HBV is more apt to cause intrafamilial transmission and induce liver cirrhosis and hepatocellular carcinoma(HCC).HBV vaccination effectively prevents the occurrences of chronic HBV infection,liver cirrhosis,and HCC.Chronic HBV infection accounts for 84.4%of HCC causes in China's Mainland.HBV promotes hepatocarcinogenesis via high replication,mutation and viral integration into the host genome.High replication of HBV activates and maintains inflammatory microenvironment that induces and selects the hepatocytes with somatic mutations and mutated HBV.Compared to the wild type,the oncogenic potential of HBV is significantly enhanced in mutated forms.The mutated HBV promotes the retro-differentiation of the mutated hepatocytes via activating key signaling pathways in the inflammatory microenvironment.HBV integration facilitates the selective growth advantage of the mutated hepatocytes via inactivating tumor suppressors and activating human telomerase reverse transcriptase.The high-risk HBV mutations can predict the occurrence,postoperative prognosis,and prophylactic effect of antiviral treatments.Antiviral treatments are able to significantly decrease the occurrence and postoperative prognosis,especially in those carrying HBV mutations in the core promoter region,thus fulfilling the specific prophylaxis and control of HBV-related HCC.

关 键 词：乙型肝炎病毒 肝细胞癌 流行特征 病毒进化 预防 

分 类 号：R181[医药卫生—流行病学] R512.6[医药卫生—公共卫生与预防医学]