乙型肝炎病毒所致非可控性炎症恶性转化的可能机制  

Possible Mechanisms of Malignant Transformation of Nonresolving Inflammation Caused by Chronic Infection With Hepatitis B Virus

作　　者：李自雄[1] 张琪[1] 林吉[1] 侯晓玫[1] 张宏伟[1] 曹广文[1] 

机构地区：[1]中国人民解放军第二军医大学流行病学教研室,上海200433

出　　处：《生物化学与生物物理进展》2014年第1期9-16,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金重大研究计划重点项目(91129301);国家杰出青年基金(81025015)资助项目~~

摘　　要：肝细胞癌(HCC)占我国大陆地区恶性肿瘤死亡原因的第二位,主要由乙型肝炎病毒(HBV)慢性感染所致.人类白细胞Ⅱ类抗原遗传多态性与HBV感染的慢性化有关.HBV与免疫系统相互作用导致的非可控性炎症是HBV进化和HCC发生的必要因素.持续的、非充分的抗病毒免疫对HBV变异有选择作用.在炎症促癌过程中病毒和肝细胞基因组均经历了"变异-选择-适应"的进化过程.HBV变异不但能预测HCC的发生,而且具有促癌功能.HBV在肝细胞基因组中整合,尤其是羧基端截短型X基因的整合不但促进HCC的发生和转移,而且抵抗抗病毒治疗.明确HBV致癌机制可为降低和推迟HCC的发生和转移奠定基础.Hepatocellular carcinoma （HCC）, the second cause of cancer-related death in China's Mainland, is mainly caused by chronic hepatitis B virus （HBV） infection. Genetic predisposition of human leukocyte antigen class 1I contributes to the maintenance of chronic HBV infection. Nonresolving inflammation resulted om the interaction of HBV and immune system is essential for the evolution of HBV and subsequent HCC occurrence. Persistent and insufficient antiviral immunity positively selects HBV mutants. During the inflammation-promoting carcinogenesis, genome of both HBV and hepatocyte experiences an evolutionary process of ＂mutation- selection-adaptation＂. HBV mutations not only predict but also promote the occurrence of HCC. The integration of HBV genome, especially in a form of the carboxylic-terminal truncated HBV X protein, not only promotes HCC occurrence and metastasis, but also confers the resistance to antiviral treatments. Understanding the mechanisms by which HBV induces hepatocarcinogenesis will lay the foundations for decreasing and postponing HCC occurrence and metastasis in the HBV-infected subjects.

关 键 词：慢性HBV感染 非可控性炎症 HBV突变 肝细胞癌 

分 类 号：Q78[生物学—分子生物学]