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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。
Chronic infection with hepatitis B virus (HBV) has become one of the most important public health problems in our country, resulting in a significant burden of disease. Chronic transformation from chronic HBV infection to associated liver disease often requires decades of chronic processes. Due to long-term infection, HBV under the immunocompetence of the host, passive selection of appropriate mutations for the survival of the virus, and these mutations further promote the malignant transformation of liver disease. Long-term stimulation of chronic inflammatory microenvironment caused by HBV, the body genome also occurs a large number of somatic mutations, while passive selection of the appropriate cell survival-related mutations. HBV mutation and body somatic mutation, which are selected by the body, all promote the transformation of cells toward malignancy, which is characterized by the evolution of “mutation-selection-adaptation”. In addition, genetic background differences between individuals are crucial for HBV-induced disease progression. Interactions between STAT polymorphisms of genetic pathways and HLA-associated loci and important HBV variants influence disease progression.