Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China.
Department of Medicine, Fourth People's Hospital of Shenzhen, Shenzhen, China.
J Gastroenterol. 2017 Sep;52(9):1064-1074. doi: 10.1007/s00535-017-1334-1. Epub 2017 Mar 28.
The association between the evolution of hepatitis B virus (HBV) quasispecies and the development of hepatocellular carcinoma (HCC) is unknown.
We used deep sequencing to examine the dynamics of HBV quasispecies and their relationship to HCC development. Thirty-two chronic hepatitis B (CHB) patients with HCC (HCC group) and 32 matched CHB patients without HCC (controls) were recruited. Fourteen patients from each group had serial sera available up to 9 years before the time of the present study. Deep sequencing of the HBV pre-S regions was performed. HBV quasispecies complexity, diversity, and intrapatient prevalence of pre-S deletions/mutations were analyzed.
Compared with control patients, HCC patients had a significant greater quasispecies complexity (p = 0.04 at the nucleotide level), greater diversity (p = 0.004 and 0.009 at the nucleotide level and the amino acid level respectively), and a trend of greater complexity at the amino acid level (p = 0.065). HCC patients had a higher intrapatient prevalence of pre-S deletions and point mutations (at codons 4, 27, and 167) compared with the control patients (all p < 0.05). Longitudinal observation in the sera of 14 HCC patients showed that quasispecies complexity (p = 0.027 and 0.024 at the nucleotide level and the amino acid level respectively) and diversity (p = 0.035 and 0.031 at the nucleotide level and the amino acid level respectively) increased as the disease progressed to HCC.
Increased HBV quasispecies complexity and diversity in the pre-S region, probably reflecting enhanced virus-host interplay, was associated with disease progression from CHB to HCC.
乙型肝炎病毒（HBV）准种的演变与肝细胞癌（HCC）的发生发展之间的关系尚不清楚。
我们使用深度测序来检测 HBV 准种的动态及其与 HCC 发展的关系。招募了 32 例乙型肝炎慢性感染（CHB）合并 HCC（HCC 组）和 32 例匹配的 CHB 无 HCC（对照组）患者。每个组中有 14 例患者的血清可用于本研究前 9 年的连续检测。对 HBV 前 S 区进行深度测序。分析 HBV 准种的复杂性、多样性以及前 S 缺失/突变的个体内流行率。
与对照组相比，HCC 组患者的准种复杂性显著增加（核苷酸水平，p=0.04），多样性也显著增加（核苷酸水平和氨基酸水平，p=0.004 和 0.009），并且氨基酸水平的复杂性也有增加的趋势（p=0.065）。与对照组相比，HCC 组患者的前 S 缺失和点突变（在密码子 4、27 和 167 处）的个体内流行率更高（均 p<0.05）。对 14 例 HCC 患者的血清进行纵向观察显示，准种复杂性（核苷酸水平和氨基酸水平，p=0.027 和 0.024）和多样性（核苷酸水平和氨基酸水平，p=0.035 和 0.031）随着疾病进展为 HCC 而增加。
前 S 区 HBV 准种复杂性和多样性的增加，可能反映了病毒-宿主相互作用的增强，与从 CHB 进展为 HCC 有关。
