Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients.
Viral and immune factors associated with successful treatment withdrawal in HBeAg-negative chronic hepatitis B patients.
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DOI：
10.1016/j.jhep.2020.11.043
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发表时间：
2021-05
影响因子：
25.7
通讯作者：
Pérez-Del-Pulgar S
中科院分区：
文献类型：
--
作者：
García-López M;Lens S;Pallett LJ;Testoni B;Rodríguez-Tajes S;Mariño Z;Bartres C;García-Pras E;Leonel T;Perpiñán E;Lozano JJ;Rodríguez-Frías F;Koutsoudakis G;Zoulim F;Maini MK;Forns X;Pérez-Del-Pulgar S
HBeAg阴性慢性B型肝炎（CH B）患者停用核苷（酸）类似物（NA）治疗后成功结局的相关因素尚未阐明。本研究的目的是分析HBV特异性T细胞反应，同时外周和肝内病毒参数，在接受NA停药的患者。前瞻性研究了27例无肝硬化、HBeAg阴性、病毒完全抑制（>3年）的CHB患者。在基线时定量肝内HBV-DNA（iHBV-DNA）、肝内HBV-RNA（iHBV-RNA）和共价闭合环状DNA（cccDNA）。此外，在基线和整个随访期间纵向分析血清标志物（HBV-DNA、HBsAg、HBV核心相关抗原[HBcrAg]和HBV-RNA）和HBV特异性T细胞应答。中位随访34个月后，22/27例患者（82%）仍停止治疗，其中8例患者（占总队列的30%）HBsAg丢失。基线HBsAg与iHBV-DNA和iHBV-RNA显著相关，并且在HBsAg丢失的患者中这些参数较低。所有患者的可检测cccDNA水平相似，无论其临床结局如何。达到功能性治愈的患者的基线HBsAg水平≤ 1，000 IU/ml。类似地，基线时功能性HBV特异性CD 8 + T细胞的频率增加与治疗后持续的病毒控制相关。这些HBV特异性T细胞反应持续存在，但在停药后没有增加。HBV特异性CD 4 + T细胞应答也观察到类似但无统计学意义的趋势。cccDNA转录降低和低HBsAg水平与HBeAg阴性CHB患者停用NA后HBsAg丢失相关。基线时功能性HBV特异性T细胞的存在与治疗停止后的成功结局相关。在没有肝硬化的慢性B型肝炎患者中，很大一部分患者可以停止核苷（酸）类似物治疗。HBV特异性免疫T细胞应答的强度可能有助于在抗病毒治疗中断后成功控制病毒。我们的综合研究提供了病毒学和免疫学因素的深入数据，有助于指导慢性B型肝炎患者的个体化治疗。在HBeAg阴性的CHB患者中，停止NA是可行的。低基线HBsAg滴度识别将实现功能性治愈的患者。cccDNA活性降低与NA停药后HBsAg丢失相关。HBV特异性T细胞功能可能会影响NA停药后患者的结局。
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. 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. 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. 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. 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. 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.
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DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
25.7
作者：
Lebosse, Fanny;Testoni, Barbara;Zoulim, Fabien
通讯作者：
Zoulim, Fabien
影响因子：
25.7
作者：
Chen, Chien-Hung;Lu, Sheng-Nan;Lee, Chuan-Mo
通讯作者：
Lee, Chuan-Mo
影响因子：
24.5
作者：
Gill, Upkar S.;Pallett, Laura J.;Maini, Mala K.
通讯作者：
Maini, Mala K.
影响因子：
7.6
作者：
Chi, H.;Hansen, B. E.;Janssen, H. L. A.
通讯作者：
Janssen, H. L. A.