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Role of anti-HBs in functional cure of HBeAg+ chronic hepatitis B patients infected with HBV genotype A
Journal of Hepatology ( IF 25.7 ) Pub Date : 2021-08-08 , DOI: 10.1016/j.jhep.2021.07.031
Hui Xu 1 , Stephen Locarnini 1 , Darren Wong 2 , Rachel Hammond 1 , Danni Colledge 1 , Sally Soppe 3 , Thao Huynh 1 , Tim Shaw 1 , Alexander J Thompson 4 , Peter A Revill 1 , P Mark Hogarth 5 , Bruce D Wines 5 , Renae Walsh 6 , Nadia Warner 1
Affiliation  

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.



中文翻译:

抗-HBs在HBV基因A型感染HBeAg+慢性乙型肝炎患者功能性治愈中的作用

背景与目标

在慢性乙型肝炎感染 (CHB) 期间很难检测到 HBsAg 特异性抗体反应,并且经常被忽视。本研究的目的是通过使用一组特定测定分析 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

纵向血清样本取自 25 名感染 HBV 基因 A 型并正在接受核苷(酸)类似物(NA)治疗的 CHB 患者:14 人获得 FC,而 11 人仍然感染(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 患者中,在 HBsAg 消失之前检测到 HBsAg-IC 峰。这些 HBsAg-IC 峰与丙氨酸氨基转移酶 (ALT) 发作(8/10 患者)或 ALT 升高(2/10 患者)重叠。在 7/11 非 FC 患者中检测到 HBsAg-IC 峰,但与 ALT 耀斑无关。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 患者在整个研究中具有稳定的 HBsAg 表位占据,而非 FC 患者在 NA 治疗的前 12-24 周内 HBsAg 表位占据减少。来自 FC 患者的恢复期血清识别更多的 HBsAg 表位,并且比来自疫苗接种者的抗 HBs 更有效地中和 HBV 感染。中和效力似乎增加了检查的 4/5 FC 患者的 HBsAg 后丢失。

结论

使用这些检测方法,我们证实在这组 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 A 型并接受了 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 中的作用。

总结

使用一组测定来表征一组慢性乙型肝炎患者的乙型肝炎表面抗体(抗 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。功能性治愈与与丙氨酸氨基转移酶耀斑重叠的免疫复合物峰相关。相反,在未实现功能性治愈的患者中,存在免疫复合物峰值,但与丙氨酸氨基转移酶发作无关,并且在治疗早期观察到抗 HBs 多样性下降。

更新日期:2021-08-08
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