结合病毒准种多样性和乙型肝炎核心相关抗原预测HBeAg阴性患

StephenW

Combined viral quasispecies diversity and hepatitis B core-related antigen predict off-nucleos(t)ide analog durability in HBeAg-negative patients

    April 2021Hepatology International

    DOI: 10.1007/s12072-021-10186-7

    Huei-Ru ChengHung-Chih YangSu-Ru LinSu-Ru Lin

    Jia-Horng KaoJia-Horng Kao

0.2
Citations
0
Recommendations
0 new
0
5 new
5
Article
Combined viral quasispecies diversity and hepatitis B core-related antigen predict off-nucleos(t)ide analog durability in HBeAg-negative patients
Share on Twitter
Recommend this work
Get updates
Share in a message
Related research
Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters
Article
Full-text available

    February 2021

Download
View more
Abstract
Background: Viral quasispecies dynamics between pre- and post-nucleos(t)ide analog (NA) therapy remains unclear. Aim: This study aimed to investigate the HBV quasispecies evolution and its relationship with durability of off-therapy responses in HBeAg-negative chronic hepatitis B (CHB) patients who stopped NA therapy. Methods: Fifty-four HBeAg-negative CHB patients who stopped NAs, including 19 virological controllers (VC) who maintained serum HBV DNA < 2000 IU/mL beyond 1-year off-therapy, and 35 virological relapsers (VR) experiencing virological relapse within 1-year off-therapy were recruited. Viral quasispecies was analyzed by deep sequencing. Hepatitis B core-related antigen (HBcrAg) and HBsAg were also measured. Results: VC had significantly higher baseline viral quasispecies diversity of the precore/core gene, measured by nucleotide diversity, than VR. Low baseline viral nucleotide diversity (< 0.01) and high HBcrAg (≧ 2.0 KU/mL), but not HBsAg, at end of treatment (EOT) were significantly associated with higher risk of 1-year virological relapse (hazard ratio [HR] 6.09 and 3.31, respectively). Combination of low baseline viral nucleotide diversity and high HBcrAg at EOT could identify patients at high risk (HR 15.82). Further analysis of the evolution of HBV whole genome showed that HBV nucleotide diversity negatively correlated with serum HBV DNA levels. Notably, the viral quasispecies diversity between pre- and post-NA treatment remained relatively unchanged. Conclusion: Higher baseline HBV quasispecies diversity associates with more durable off-therapy viral suppression in HBeAg-negative CHB patients. Combination of baseline viral nucleotide diversity and HBcrAg at EOT can identify patients at high risk for virological relapse after stopping NAs.

StephenW

结合病毒准种多样性和乙型肝炎核心相关抗原预测HBeAg阴性患者的核外（t）ide类似物持久性

    2021年4月

    DOI：10.1007 / s12072-021-10186-7

    许辉如郑鸿志杨素如林素如

    高家宏高家宏

0.2
引文
0
推荐建议
0新
0
5个新
5
文章
结合病毒准种多样性和乙型肝炎核心相关抗原预测HBeAg阴性患者的核外（t）ide类似物持久性
分享到Twitter
推荐这项工作
获取更新
分享讯息
相关研究
HBeAg血清转化者中病毒准种多样性和进化的全基因组深度测序分析
文章
全文可用

    2021年2月

下载
查看更多
抽象的
背景：核苷酸（t）核苷酸类似物（NA）治疗之前和之后的病毒准种动态仍然不清楚。目的：本研究旨在调查在停止NA治疗的HBeAg阴性慢性乙型肝炎（CHB）患者中HBV准种的进化及其与非治疗应答持续性的关系。方法：54例停止NAs的HBeAg阴性CHB患者，包括19名病毒治疗者（VC）在治疗后一年内维持血清HBV DNA <2000 IU / mL，以及35名病毒复发者（VR）在此疗程内复发招募了1年的非治疗药物。通过深度测序分析病毒准种。还测量了乙型肝炎核心相关抗原（HBcrAg）和HBsAg。结果：通过核苷酸多样性来衡量，VC的precore / core基因的基线病毒拟种多样性显着高于VR。治疗结束（EOT）时，基线病毒核苷酸多样性低（<0.01）和高HBcrAg（≥2.0 KU / mL），而不是HBsAg与1年病毒学复发的较高风险显着相关（危险比[HR] 6.09和3.31）。 EOT时基线病毒核苷酸多样性低和HBcrAg高相结合可以确定高危患者（HR 15.82）。对HBV全基因组进化的进一步分析表明，HBV核苷酸多样性与血清HBV DNA水平呈负相关。值得注意的是，NA前和后治疗之间的病毒准种多样性保持相对不变。结论：HBeAg阴性CHB患者较高的基线HBV准种多样性与更持久的非治疗性病毒抑制有关。在EOT时，基线病毒核苷酸多样性和HBcrAg的结合可以识别出在停止NAs后有病毒学复发高风险的患者。