时代在改变-有限的HBV核苷酸模拟疗法的完善建议

StephenW

The times they are a-changing – A refined proposal for finite HBV nucleos(t)ide analog therapy
May 03, 2021 - Jnl of Hepatology - Thomas Berg, Pietro Lampertico
Abstract
Although discontinuation of nucleos(t)ide analogue (NA) treatment before HBsAg loss is part of all current hepatitis B virus (HBV) treatment guidelines for HBeAg-positive patients who achieved HBeAg seroconversion, a treatment endpoint known to be associated with silencing of HBV transcriptional activity and restoration of HBV-specific immune control, it is still highly controversial whether it is even appropriate to consider NA discontinuation before HBsAg loss in the HBeAg-negative phase. Despite the growing evidence that a relevant, albeit small, proportion of patients with HBeAg-negative disease can be cured by stopping NA treatment, the fear of discontinuation-associated relapse and the uncertainty of how to predict off-therapy response and monitor patients after discontinuation have generated scepticism and subsequently led to low implementation of this concept in the clinic. In this article, we propose a concept in which NA discontinuation-associated relapse is an integral part of the stop-to-cure approach and ultimately the trigger for achieving HBsAg loss. However, the relapse in this sense only becomes functionally effective if HBV-specific immune reinvigoration and silencing of HBV transcriptional activity have been achieved previously under the NA treatment period. The probability with which a functional cure can be achieved but also the severity of post-discontinuation flares depends on the underlying baseline HBV transcriptional activity when NA was started as well as the duration of NA treatment, both factors that we should consider as we move towards individualised cure approaches in the future.

StephenW

时代在改变-有限的HBV核苷酸模拟疗法的完善建议
2021年5月3日-肝病学杂志-托马斯·伯格，彼得罗·兰佩蒂科
抽象的
尽管在HBsAg丢失之前停止核苷酸类似物（NA）治疗是目前所有实现HBeAg血清转化的HBeAg阳性患者的所有乙型肝炎病毒（HBV）治疗指南的一部分，已知该治疗终点与HBV沉默有关转录活性和HBV特异性免疫控制的恢复，是否在HBsAg阴性阶段HBsAg丢失之前考虑NA停药是否仍然是一个有争议的问题。尽管越来越多的证据表明，通过停止NA治疗可以治愈相关但很小的HBeAg阴性患者比例，对与停药相关的复发的恐惧以及停药后如何预测非治疗反应和监测患者的不确定性引起了怀疑，并随后导致该概念在临床中的实施率较低。在本文中，我们提出了一个概念，其中NA终止相关的复发是“从一站式”治疗方法不可或缺的组成部分，并最终成为实现HBsAg损失的触发因素。然而，从这个意义上讲，这种复发仅在先前在NA治疗期间已经实现了HBV特异性免疫增强和HBV转录活性沉默的情况下才有效。功能性治愈的可能性以及停药后发作的严重程度取决于开始NA时基本的基础HBV转录活性以及NA治疗的持续时间，这是我们朝着前进的方向应考虑的两个因素未来的个性化治疗方法。

StephenW

https://natap.org/2021/HBV/PIIS0168827821003056.pdf

StephenW

这是一个新的大胆的建议 . Berg和Lampertico都是著名的HBV研究人员,他们已经广泛研究了干扰素联合治疗和停药规则, 现在NA停用。