与HBeAg阴性慢性乙型肝炎患者成功退出治疗相关的病毒和免疫

StephenW

Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients

    Mireia García-López †
    Sabela Lens †
    Laura J. Pallett
    Mala K. Maini
    Xavier Forns
    Sofía Pérez-del-Pulgar
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Open AccessPublishedecember 02, 2020DOI:https://doi.org/10.1016/j.jhep.2020.11.043


Highlights

    •
    Stopping NA is feasible in a high proportion of HBeAg-negative CHB patients.
    •
    Low baseline HBsAg titres identify patients who will achieve functional cure.
    •
    Reduced cccDNA activity is associated with HBsAg loss after NA discontinuation.
    •
    HBV-specific T cell functionality may influence patient outcome upon NA withdrawal.

Background & Aims
Factors associated with a successful outcome upon nucleos(t)ide analogue (NA) treatment withdrawal in HBeAg-negative chronic hepatitis B (CHB) patients have yet to be clarified. The objective of this study was to analyse the HBV-specific T cell response, in parallel with peripheral and intrahepatic viral parameters, in patients undergoing NA discontinuation.
Methods
Twenty-seven patients without cirrhosis with HBeAg-negative CHB with complete viral suppression (>3 years) were studied prospectively. Intrahepatic HBV-DNA (iHBV-DNA), intrahepatic HBV-RNA (iHBV-RNA), and covalently closed circular DNA (cccDNA) were quantified at baseline. Additionally, serum markers (HBV-DNA, HBsAg, HBV core-related antigen [HBcrAg] and HBV-RNA) and HBV-specific T cell responses were analysed at baseline and longitudinally throughout follow-up.
Results
After a median follow-up of 34 months, 22/27 patients (82%) remained off-therapy, of whom 8 patients (30% of the total cohort) lost HBsAg. Baseline HBsAg significantly correlated with iHBV-DNA and iHBV-RNA, and these parameters were lower in patients who lost HBsAg. All patients had similar levels of detectable cccDNA regardless of their clinical outcome. Patients achieving functional cure had baseline HBsAg levels ≤1,000 IU/ml. Similarly, an increased frequency of functional HBV-specific CD8+ T cells at baseline was associated with sustained viral control off treatment. These HBV-specific T cell responses persisted, but did not increase, after treatment withdrawal. A similar, but not statistically significant trend, was observed for HBV-specific CD4+ T cell responses.
Conclusions
Decreased cccDNA transcription and low HBsAg levels are associated with HBsAg loss upon NA discontinuation in patients with HBeAg-negative CHB. The presence of functional HBV-specific T cells at baseline are associated with a successful outcome after treatment withdrawal.
Lay summary
Nucleos(t)ide analogue therapy can be discontinued in a high proportion of chronic hepatitis B patients without cirrhosis. The strength of HBV-specific immune T cell responses may contribute to successful viral control after antiviral treatment interruption. Our comprehensive study provides in-depth data on virological and immunological factors than can help guide individualised therapy in patients with chronic hepatitis B.

StephenW

与HBeAg阴性慢性乙型肝炎患者成功退出治疗相关的病毒和免疫因素

    米雷亚·加西亚·洛佩斯（MireiaGarcía-López）†
    萨贝拉·伦斯（Sabela Lens）†
    劳拉·帕列特（Laura J.Pallett）
    玛拉·迈因尼（Mala K. Maini）
    泽维尔·福恩斯
    索非亚·佩雷斯·德尔·普尔加（SofíaPérez-del-Pulgar）
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开放获取发布时间：2020年12月2日DOI：https：//doi.org/10.1016/j.jhep.2020.11.043


强调

    •
    在很大比例的HBeAg阴性CHB患者中，停止NA是可行的。
    •
    低基线HBsAg滴度可识别出可以治愈的患者。
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    cccDNA活性降低与NA停用后HBsAg丢失有关。
    •
    HBV特异性T细胞功能可能会在NA停用后影响患者预后。

背景与目标
在HBeAg阴性的慢性乙型肝炎（CHB）患者中，与核苷酸（t）ide类似物（NA）治疗撤药成功相关的因素尚未阐明。这项研究的目的是分析NA停药患者的HBV特异性T细胞反应，以及外周和肝内病毒参数。
方法
前瞻性研究了27例无肝硬化的HBeAg阴性CHB并完全抑制病毒（> 3年）的患者。在基线时对肝内HBV-DNA（iHBV-DNA），肝内HBV-RNA（iHBV-RNA）和共价闭合环状DNA（cccDNA）进行定量。此外，在整个随访过程中，在基线和纵向分析了血清标志物（HBV-DNA，HBsAg，HBV核心相关抗原[HBcrAg]和HBV-RNA）和HBV特异性T细胞反应。
结果
在平均随访34个月后，仍有22/27例患者（占82％）停止治疗，其中8例患者（占总队列的30％）失去了HBsAg。基线HBsAg与iHBV-DNA和iHBV-RNA显着相关，并且这些参数在丢失HBsAg的患者中较低。无论临床结果如何，所有患者均具有相似水平的可检测cccDNA。达到功能治愈的患者的基线HBsAg水平≤1,000IU / ml。同样，基线时功能性HBV特异性CD8 + T细胞的频率增加与持续的病毒控制关闭治疗相关。在停药后，这些HBV特异性T细胞反应持续存在，但没有增加。对于HBV特异性CD4 + T细胞反应，观察到类似但无统计学意义的趋势。
结论
HBsAg阴性CHB患者NA停用后，cccDNA转录水平降低和HBsAg水平降低与HBsAg丢失有关。基线时功能性HBV特异性T细胞的存在与停药后的成功预后相关。
放置摘要
在大部分没有肝硬化的慢性乙型肝炎患者中，可以停止使用核苷类似物治疗。抗病毒治疗中断后，HBV特异性免疫T细胞反应的强度可能有助于成功控制病毒。我们的综合研究提供了有关病毒学和免疫学因素的深入数据，可帮助指导慢性乙型肝炎患者的个体化治疗

StephenW

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