抗-HBs在乙型肝炎病毒基因A型感染的HBeAg+慢性乙型肝炎患者功

StephenW

抗-HBs在乙型肝炎病毒基因A型感染的HBeAg+慢性乙型肝炎患者功能性治愈中的作用

    许慧
    斯蒂芬·洛卡尼尼
    黄达伦
    布鲁斯 D. 葡萄酒
    雷娜·沃尔什
    娜迪亚华纳
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发布时间：2021年8月6日DOI：https://doi.org/10.1016/j.jhep.2021.07.031
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强调

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    在 10/14 FC 患者的 HBs 消失之前，检测到与 ALT 升高或 ALT 升高同时出现的 HBsAg-IC 峰。
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    在 9/14 FC 患者中检测到 FcγRIIIa 二聚体结合，与重叠的 HBsAg-IC/ALT 峰的检测无关。
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    在非 FC 患者的治疗 12 至 24 周之间观察到 HBsAg 表位占有率降低。
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    恢复期血清识别更多的 HBsAg 表位并比接种者的血清更有效地中和 HBV 感染。
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    在接受检查的 4/5 FC 患者 HBsAg 消失后 100 周，血清的中和效力增加。

背景与目标
HBsAg 特异性抗体反应在慢性乙型肝炎感染 (CHB) 期间很难检测到，并且经常被忽视。本研究的目的是通过使用一组特定测定法分析 CHB 患者的抗 HBs 反应来检查抗 HBs 是否可能参与功能性治愈 (FC)。
方法
从 25 名感染了 HBV 基因型 A 并正在接受核苷（酸）类似物 (NA) 治疗的 CHB 患者获得纵向血清样本：14 名达到 FC，而 11 名仍然感染（非 FC）。测量了抗 HBs 免疫复合物 (HBsAg-IC)、FcγRIIIa 二聚体结合、表位特异性和中和功效。
结果
在 10/14 FC 患者 HBsAg 消失之前检测到 HBsAg-IC 峰。这些 HBsAg-IC 峰与丙氨酸转氨酶 (ALT) 爆发（8/10 名患者）或 ALT 升高（2/10 名患者）重叠。在 7/11 非 FC 患者中检测到 HBsAg-IC 峰，但与 ALT 爆发无关。在 9/14 FC 患者中检测到 FCγRIIIa 结合，独立于重叠 HBsAg-IC/ALT 峰的检测。 FC 患者在整个研究中的 HBsAg 表位占有率稳定，而非 FC 患者在 NA 治疗的前 12-24 周内 HBsAg 表位占有率降低。与来自疫苗接种者的抗 HBs 相比，来自 FC 患者的恢复期血清识别出更多的 HBsAg 表位并更有效地中和 HBV 感染。在所检查的 4/5 FC 患者中，中和效力似乎增加了 HBsAg 后的消失。
结论
使用这些测定，我们确认在这组 HBeAg+ CHB 患者中存在抗 HBs 反应并随时间波动，这些患者感染了 HBV 基因型 A 并接受了 NAs 治疗。还确定了与 FC 或未能实现 FC 相关的关键抗 HBs 谱，表明抗 HBs 反应在 FC 中起作用。
奠定总结
使用一组检测来表征一组慢性乙型肝炎患者的乙型肝炎表面抗体 (anti-HBs) 反应，我们确定了与功能性治愈或未能实现功能性治愈相关的抗 HBs 谱。功能性治愈与免疫复合物峰值有关，这些峰值与丙氨酸氨基转移酶的爆发重叠。相反，在未实现功能性治愈的患者中，存在免疫复合物峰值，但与丙氨酸转氨酶升高无关，并且在治疗早期观察到抗 HBs 多样性下降。

StephenW

Role of anti-HBs in functional cure of HBeAg+ chronic hepatitis B patients infected with HBV genotype A

    Hui Xu
    Stephen Locarnini
    Darren Wong
    Bruce D. Wines
    Renae Walsh
    Nadia Warner
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Published:August 06, 2021DOI:https://doi.org/10.1016/j.jhep.2021.07.031
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Highlights

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    HBsAg-IC peaks that coincided with either an ALT flare or a rise in ALT were detected before HBs-loss in 10/14 FC patients.
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    FcγRIIIa dimer binding was detected in 9/14 FC patients, independent of detection of overlapping HBsAg-IC/ALT peaks.
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    A reduction in HBsAg epitope occupancy was observed between 12 and 24 weeks of treatment in non-FC patients.
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    Convalescent sera recognised more HBsAg epitopes and neutralized HBV infection more potently than vaccinees' sera.
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    Neutralisation potency of sera increased up to 100 weeks after HBsAg loss in 4/5 FC patients examined.

Background & Aims
HBsAg-specific antibody responses are difficult to detect during chronic hepatitis B infection (CHB) and are often overlooked. The aim of this study was to examine whether anti-HBs may be involved in functional cure (FC) by profiling anti-HBs responses in patients with CHB using a panel of specific assays.
Methods
Longitudinal serum samples were obtained from 25 patients with CHB who were infected with HBV genotype A and were undergoing nucleos(t)ide analogue (NA) treatment: 14 achieved FC while 11 remained infected (non-FC). Anti-HBs immune complexes (HBsAg-IC), FcγRIIIa dimer binding, epitope specificity and neutralisation efficacy were measured.
Results
HBsAg-IC peaks were detected prior to HBsAg loss in 10/14 FC patients. These HBsAg-IC peaks overlapped with either an alanine aminotransferase (ALT) flare (8/10 patients), or a rise in ALT (2/10 patients). HBsAg-IC peaks were detected in 7/11 non-FC patients, but were not associated with an ALT flare. FCγRIIIa binding was detected in 9/14 FC patients, independent from detection of overlapping HBsAg-IC/ALT peaks. FC patients had stable HBsAg epitope occupancy across the study, whereas non-FC patients had a reduction in HBsAg epitope occupancy within the first 12–24 weeks of NA treatment. Convalescent sera from FC patients recognised more HBsAg epitopes and neutralised HBV infection more potently than anti-HBs derived from vaccinees. Neutralisation potency appeared to increase post-HBsAg loss in 4/5 FC patients examined.
Conclusions
Using these assays, we confirm that anti-HBs responses are present and fluctuate over time in this cohort of patients with HBeAg+ CHB, who were infected with HBV genotype A and treated with NAs. Key anti-HBs profiles associated with either FC or failure to achieve FC were also identified, suggesting a role for anti-HBs responses in FC.
Lay summary
Using a panel of assays to characterise hepatitis B surface antibody (anti-HBs) responses in a group of patients with chronic hepatitis B, we identified anti-HBs profiles associated with either functional cure, or failure to achieve functional cure. Functional cure was associated with immune complex peaks which overlapped with alanine aminotransferase flares. Conversely, in those who did not achieve functional cure, immune complex peaks were present, but were not associated with alanine aminotransferase flares, and a decline in anti-HBs diversity was observed early during treatment.