Hepatitis B virus preCore/Core region complexity by massive sequencing

Recent reports support the concept that HBV quasispecies (QA) complexity is a clinically relevant factor in the course and prognosis of this disease and in the response to treatment. The preCore/Core is an optimal region to investigate QA evolution, in relation to host immune system stimulation and regulation of HBV replication. Up to day, the evolution of the preCore/Core regions under NUC treatment has been little investigated. The aim of this study is to evaluate HBV quasispecies (QA) complexity in the preCore/Core regions in relation to HBeAg status, and explore QA changes under natural evolution and nucleoside analogue (NUC) treatment. To achieve that goals, preCore/Core regions have been analyzed by ultra-deep pyrosequencing in 30 sequential samples (baseline [diagnosis], treatment-free, and treatment-nonresponse) from 10 retrospectively selected patients.

已有近期研究证实，乙型肝炎病毒（Hepatitis B Virus, HBV）准种（QA）的复杂度是影响该疾病病程、预后及治疗应答的临床相关因素。前核心/核心（preCore/Core）区域是研究准种进化的最优靶点，该区域与宿主免疫系统的激活及HBV复制的调控密切相关。迄今为止，针对核苷类似物（nucleoside analogue, NUC）治疗过程中前核心/核心区准种进化的相关研究仍较为匮乏。本研究旨在评估前核心/核心区HBV准种（QA）的复杂度与乙型肝炎e抗原（Hepatitis B e antigen, HBeAg）状态的相关性，并探究准种在自然进化及核苷类似物（NUC）治疗过程中的动态变化。为达成上述研究目标，本研究对10名回顾性筛选患者的30份连续样本（包括基线[诊断时]、未接受治疗及治疗无应答样本）采用超深度焦磷酸测序技术对前核心/核心区进行了分析。