免疫预防失败后婴儿期HBV准种多样性的动态变化：一项前瞻

StephenW

免疫预防失败后婴儿期HBV准种多样性的动态变化：一项前瞻性队列研究

    Yi Li、Yiwei Xiao、Lili Li、Yong Song、Xiangzhai、Jianxun Liu、Zhongping Duan、Ling Yan、Feng Ding、Jia Liu、Liguo Zhu、Jie Jiang、Zaibin Zou、Lingxiang Li、Caihong Liang、Jie Wang & Jie Li

病毒学杂志第 18 卷，文章编号：236 (2021) 引用此文章

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抽象的
背景

以前的工作观察到，患有慢性乙型肝炎病毒 (HBV) 感染的年幼婴儿对抗病毒治疗的反应更灵敏。然而，潜在的机制仍不清楚。本研究通过研究免疫预防失败婴儿HBV准种的动态变化，为婴儿抗病毒治疗的临床管理提供病毒学解释。
方法

从前瞻性队列中招募了 13 名 7 个月大的免疫预防失败婴儿及其母亲，其中 8 名被随访至 3 岁。通过全长基因组克隆测序分析HBV准种序列，并在不同年龄段的母婴之间进行比较。
结果

结果显示，与母亲相比，7月龄婴儿HBV准种的复杂性、突变频率和遗传距离在核苷酸水平的HBV基因组全长、部分开放阅读框和调控区均显着降低，而在核苷酸水平上显着增加婴儿长到 3 岁时接近母体水平。此外，在氨基酸水平上，HBV基因组的Core、PreS2、RT和P区也发现了类似的变化，尤其是RT区潜在的NAs抗性突变体和Core和PreS2区的免疫逃逸突变体。
结论

本研究揭示了母婴传播后婴儿期HBV准种的演变，这可能为解释年龄较小的儿童对抗病毒治疗的反应性更强提供病毒学证据。

StephenW

The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: a prospective cohort study

    Yi Li, Yiwei Xiao, Lili Li, Yarong Song, Xiangjun Zhai, Jianxun Liu, Zhongping Duan, Ling Yan, Feng Ding, Jia Liu, Liguo Zhu, Jie Jiang, Huaibin Zou, Lingxiang Li, Caihong Liang, Jie Wang & Jie Li

Virology Journal volume 18, Article number: 236 (2021) Cite this article

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Abstract
Background

Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy.
Methods

Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages.
Results

The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions.
Conclusions

This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.

StephenW

https://virologyj.biomedcentral. ... /s12985-021-01707-9

StephenW

"幸运的是，对儿童慢性乙型肝炎 (CHB) 患者进行抗病毒治疗的大多数研究都显示出有希望的结果，病毒控制率、HBeAg 血清学转换和 HBsAg 消失率显着提高 [3,4,5,6,7,8 ,9]。 同时，免疫耐受 (IT) 阶段 HBV 感染婴儿的抗病毒疗效也显示出令人鼓舞的结果，61-78% 的婴儿实现了 HBV DNA 丢失，22-39% 实现了 HBeAg 血清学转换，17-22% 实现了 HBsAg 消失。 10、11、12、13]。 而且，最近的一项研究表明，1岁前接受抗病毒治疗的婴儿比1岁后接受抗病毒治疗的婴儿获得更多的益处，HBsAg消失率为83%，治疗持续时间更短，不良事件发生率更低[14]。 总体而言，大多数研究表明，年轻患者对抗病毒治疗的反应更灵敏，这表明初始治疗的时机至关重要。 然而，潜在的机制尚不清楚。"
Fortunately, most of the studies conducted on antiviral therapy in pediatric chronic hepatitis B (CHB) patients have shown promising results with significant improvements in the rates of viral control, HBeAg seroconversion and HBsAg loss [3,4,5,6,7,8,9]. Meanwhile, the antiviral efficacy of HBV-infected infants at immune tolerant (IT) stage also showed encouraging outcomes with 61–78% of infants achieved HBV DNA loss, 22–39% achieved HBeAg seroconversion, and 17–22% achieved HBsAg loss [10,11,12,13]. Moreover, a recent study showed that the infants receiving antiviral therapies before 1 year old obtained more benefits than those receiving antiviral therapies after 1 year old, with 83% of HBsAg loss, shorter treatment duration and lower incidence of adverse events [14]. Overall, most of the studies showed that the younger patients were more responsive to antiviral treatment, suggesting the timing of the initial treatment is crucial. However, the underlying mechanisms are unclear.