HBV变异、体细胞变异及相关免疫遗传在肝硬化和肝细胞癌发生中的作用

Role of hepatitis B virus mutation,somatic mutations of hosts and related immune genetics in liver cirrhosis and hepatocellular carcinoma

乙型肝炎病毒(hepatitis B virus,HBV)慢性感染已经成为我国最重要公共卫生问题之一,造成重大的疾病负担。从HBV慢性感染状态到相关肝脏疾病的恶性转化,常需要数十年的慢性过程。由于长期感染,HBV在宿主的免疫压力下,被动选择出适合病毒生存的相关突变,而这些突变又进一步促进肝脏疾病的恶性转化。在HBV引起的慢性炎症微环境的长期刺激下,机体基因组也发生大量的体细胞突变,同时被动选择出适合细胞存活的相关突变。被机体选择出来的HBV变异和机体体细胞变异,均促使细胞向恶性方向转变,表现为"变异-选择-适应"的进化过程。此外,不同个体之间的遗传背景差异对HBV导致的疾病进程至关重要,如STAT通路和HLA相关位点的基因多态性与重要HBV变异的交互作用影响疾病进展。

Hepatitis B virus（HBV）infection has always been one of the most important public health issues in China's Mainland,causing a huge disease burden.It often takes decades for the chronic process of malignant transformation from HBV infection to different stages of liver diseases.Mutations associated with virus survival are eventually selected by the chronic infection process and under the immune pressure of host.These selected HBV mutations further promote the malignant transformation of liver diseases.A large amount of somatic mutations are produced in the HBV-related chronic inflammatory micro-environment,and those survival-related mutations will then be selected.The selected HBV mutations and host somatic mutations work together to promote the malignant transformation,which can be termed as an evolutionary process of＂mutation-selection-adaptation＂.In addition,genetic variations of individual hosts also play an important role in HBV related disease progression.For example,single-nucleotide polymorphisms of STAT pathway and HLA can interact with important HBV mutations and therefore affect HBV-related disease progression.