Increased hepatitis B virus quasispecies diversity is correlated with liver fibrosis progression
Increased hepatitis B virus quasispecies diversity is correlated with liver fibrosis progression
复制标题
乙型肝炎病毒准种多样性增加与肝纤维化进展相关
DOI：
10.1016/j.meegid.2021.104938
复制
发表时间：
2021
影响因子：
3.2
通讯作者：
Zhanhui Wang
中科院分区：
文献类型：
--
作者：
Hongkai Wu;Baolin Liao;Xueying Li;Huiyuan Liu;Mingxing Gong;Haiyan Shi;Shi Xie;Fengxia Guo;Keng Chen;Rong Yan;Han Zhao;Liya Li;Anqi Zheng;Yu Liu;Zhanhui Wang
宿主免疫反应和病毒因子参与了慢性乙型肝炎病毒感染患者的疾病进展。然而，乙肝病毒准种与肝纤维化进展之间的关系仍不清楚。本研究共纳入447例慢性乙肝患者，其中慢性乙型肝炎239例，肝硬变104例，肝细胞癌104例。239例慢性乙型病毒性肝炎患者按肝纤维化评分分为F1、F2、F3组。使用下一代测序技术对四个乙肝病毒基因组片段进行了测定和分析。BCP/PC区的A1762T、G1764A和G1896A等特定突变在晚期肝病患者中更为常见，并形成了LC和肝癌患者中的大多数病毒准种库。病毒的复杂性和多样性随着纤维化的进展而增加，特别是在年龄相似但处于不同纤维化阶段的慢性乙肝患者中。早期纤维化患者在四个测序区经历了较高的纯化选择压力，而不同的蛋白编码区随着疾病的进展经历了不同的阴性选择。在免疫选择下，随着年龄的增长，HBV准物种多样性可能会增加CHB患者的纤维化进程。
Host immune response and viral factors are involved in disease progression in patients with chronic hepatitis B virus (HBV) infection. However, the relationship between HBV quasispecies and liver fibrosis progression remains unclear. In this study, 447 patients with chronic HBV infection, including 239 with chronic hepatitis B (CHB), 104 with liver cirrhosis (LC) and 104 with hepatocellular carcinoma (HCC) were enrolled. The 239 CHB patients were divided into groups F1, F2, and F3 according to liver fibrosis score. Four fragments of the HBV genome were determined and analyzed using next-generation sequencing. Specific mutations, such as A1762T, G1764A and G1896A, in the BCP/PC region were more common in patients with advanced liver disease and formed the majority of the viral quasispecies pool in patients with LC and HCC. The viral complexity and diversity increased as the fibrosis progressed, especially in patients with CHB who were comparable in age but at different stages of fibrosis. Patients with early-stage fibrosis experienced higher purifying selection pressure in the four sequenced regions, whereas different protein-coding region experienced different negative selection with disease progression. HBV quasispecies diversity may increase fibrosis progression in CHB patients with aging under immune selection.