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1.乙型肝炎重症化是病毒（病毒载量、变异、进化等）和宿主（遗传异质性、年龄、性别等）通过免疫应答相互作用导致的常见复杂疾病，涉及病毒和宿主个体的分子遗传学特性两个方面的内容，这不仅是乙型重型肝炎基础研究的核心问题，也是重大传染病发生及发展研究中的热点问题。
2.宿主遗传变异从蛋白质功能层面和免疫识别层面决定个体对病毒和环境因素反应的“质”，从转录水平、表达水平决定个体对病毒和环境因素反应的“量”，从根本上影响乙型肝炎重症化的发生与发展。
3.影响乙型肝炎重症化的宿主遗传因素包括基因的常见变异、罕见低频变异导致的遗传编码信息改变和结构功能变化，以及表观遗传修饰引起的转录和表达调控。
4.近年研究发现，多个基因如CXCL10、IL-10、TLR2、TNF-α、HLA-DR、HLA-DQ等的常见变异位点与慢性HBV感染病变重症化进展相关。基于候选基因策略的关联研究和全基因组关联研究是解析复杂疾病宿主常见特征常用的两种遗传关联研究策略，它们在揭示乙型肝炎重症化易感位点和通路方面发挥了很大作用。
5.近年来，随着新一代测序技术的发展，多项研究表明，除了常见变异外，多个基因的罕见低频变异也与慢性乙型肝炎疾病转归相关。
6.表观遗传学是研究不涉及DNA序列变化、可遗传的和可逆性的基因表达调节的一门新兴的遗传学分支。目前表观遗传学研究内容主要涉及DNA甲基化修饰、染色质组蛋白的修饰、染色质重构及非编码RNA等调控方式。目前乙型肝炎重症化表观遗传修饰的研究处于初始阶段，但日益成为未来的热点方向。
1.The exacerbation of chronichepatitis B,which is considered as a complex trait,relates to the interactions between thehepatitis B virus （viral load,variation,evaluation,etc.）andhost factors （geneticheterogeneity,age,gender,etc.）via immune response.The mechanism involved in this process is not only a key point in the pathogenesis of severehepatitis B,but also in other major infectious diseases.
2.The “quality” of an individual’s reaction to the virus and the environment is determined byhost genetic variations at both the protein and immune levels，while the “quantity” of the reaction determined by gene transcription and expression.Both fundamentally affect the occurrence and development of severehepatitis B.
3.The main genetic factors involved in exacerbationhepatitis B include common variants,rare variants in related genes,which may result in abnormal genetic-coding then alerted structure and function of its coded protein.Meanwhile,epigenetic modification of disease related gene could play a role in the progress of the disease.
4.Common variants in several genes,such as CXCL10,IL-10,TLR2,TNF-α,HLA-DR and HLA-DQ,have been reported as candidate genes/variants associated with acute exacerbation of chronichepatitis B.Two research strategies,candidate gene study and genome-wide association study,are the most common methods to analyse the association between traits and genetic markers or candidate genes based on the principle of linkage disequilibrium.
5.Recently,several rare variants are reported to be associated with acute exacerbation of chronichepatitis B due to the development of the deep sequencing technology.
6.Epigenetics，an emerging branch of genetics，does not involve changes in DNA sequence，or theheritable or reversible regulation of gene expression.Rather,epigenetics research mainly involves the regulation of DNA methylation,chromatinhistone modification,chromatin remodeling and non-coding RNA.Although epigenetic modification studies in acute exacerbation of chronichepatitis B are at their initial stage,they are expected to become more important in the future.