Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg-Negative Chronic Hepatitis B.
Risks and Benefits of Discontinuation of Nucleos(t)ide Analogue Treatment: A Treatment Concept for Patients With HBeAg-Negative Chronic Hepatitis B.
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DOI：
10.1002/hep4.1708
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发表时间：
2021-10
影响因子：
5.1
通讯作者：
Berg T
中科院分区：
文献类型：
--
作者：
van Bömmel F;Berg T
系统地停止核糖核酸类似物(NAS)的长期治疗是提高慢性乙肝e抗原(HBeAg)阴性乙肝患者功能治愈率的一种策略。目前，现有的研究结果是不同的；然而，前瞻性试验报告了高达20%的乙肝表面抗原(HBs)长期丢失率。这篇综述提出了在考虑慢性乙肝病毒(乙肝)患者停用NA时可以使用的标准。停止NA治疗通常会导致病毒学和生化复发，并经历不同的阶段：滞后阶段、重新激活阶段和巩固阶段。在重新激活阶段观察到的HBVDNA爆发通常是暂时的，很可能是特定CD8+T细胞诱导长期免疫控制的触发因素，因此不需要立即干预，但需要密切的后续评估。停药时较低的乙肝表面抗原水平预示着对NA停用的长期阳性反应与较高的乙肝表面抗原清除的可能性有关。其他宿主和病毒生物标记物目前正在评估中，可能有助于进一步描述可能从有限NA治疗概念中受益最大的人群。重新激活阶段的潜在有害生化耀斑需要及早识别，并可通过重新引入NA治疗有效地终止。肝功能失代偿对接受NA停用的肝硬变患者来说是一种风险。因此，只有在排除了晚期纤维化和肝硬变，并且可以保证患者的密切随访和有经验的内科医生的监督的情况下，才应该考虑有限NA入路。结论：对于选定的患者，停用NA已成为实现HBeAg阴性乙肝病毒感染控制的有力工具。它的显著效果代表着对新的治疗方法的挑战，但它也可能成为它们的增强剂。
Systematic discontinuation of long‐term treatment with nucleos(t)ide analogues (NAs) is one strategy to increase functional cure rates in patients with chronic hepatitis B e antigen (HBeAg)–negative hepatitis B. Currently, available study results are heterogeneous; however, long‐term hepatitis B surface antigen (HBsAg) loss rates of up to 20% have been reported in prospective trials. This review proposes criteria that can be used when considering NA discontinuation in patients with chronic hepatitis B virus (HBV). Discontinuing NA treatment frequently results in a virologic and biochemical relapse that runs through different phases: the lag phase, reactivation phase, and consolidation phase. The HBV‐DNA flares observed during the reactivation phase are often transient and most likely represent a trigger for inducing a long‐term immune control by specific CD8+ T cells, and therefore do not need immediate interventions but close follow‐up evaluation. Low HBsAg levels at the time of treatment cessation predict a positive long‐term response to NA discontinuation associated with a higher likelihood of HBsAg clearance. Other host and viral biomarkers are currently under evaluation that may prove to be helpful to further characterize the population that may benefit most from the finite NA treatment concept. Potential harmful biochemical flares during the reactivation phase need to be identified early and can be effectively terminated by reintroducing NA treatment. Hepatic decompensation represents a risk to patients with cirrhosis undergoing NA discontinuation. Therefore, the finite NA approach should only be considered after excluding advanced fibrosis and cirrhosis and if a close follow‐up of the patient and supervision by an experienced physician can be guaranteed. Conclusion: For selected patients, NA discontinuation has become a powerful tool to achieve control over HBeAg‐negative HBV infections. Its significant effect represents a challenge to novel treatment approaches, but it may also serve as their enhancer.
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