对慢性乙型肝炎患者停止核苷酸类似物治疗的看法

StephenW

Views on stopping nucleos(t)ide analogue therapy in patients with chronic hepatitis B
Issam Tout  1 , Pietro Lampertico  2 , Thomas Berg  3 , Tarik Asselah  4
Affiliations
Affiliations

    1
    University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, Inserm, F-75018 Paris, France; Department of Hepatology, AP-HP Hôpital Beaujon, Clichy 92110, France.
    2
    Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
    3
    Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
    4
    University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, Inserm, F-75018 Paris, France; Department of Hepatology, AP-HP Hôpital Beaujon, Clichy 92110, France. Electronic address: [email protected].

    PMID: 33279523 DOI: 10.1016/j.antiviral.2020.104992

Abstract

Long-term treatment with nucleos(t)ide analogs (NAs) is the current first line therapy for patients with chronic hepatitis B (CHB), recommended by most of the current guidelines. NAs prevent disease progression, liver failure, decrease the risk of hepatocellular carcinoma (HCC), and have favorable safety profiles. However, low rates of on-therapy functional cure (hepatitis B surface antigen [HBsAg] loss), which is regarded as the optimal end point, prevent many patients from stopping NA therapy with the need for a lifelong treatment. The higher likelihood of HBsAg loss associated with stopping as compared to continuing NAs has got a lot of attention lately. Recommendations regarding endpoints allowing for safely stopping NA therapy differ between the different international guidelines. Whereas in HBeAg-positive patients, HBeAg seroconversion with at least one year of consolidation therapy is an accepted endpoint of treatment, the recommendations for HBeAg-negative ones differ. Some guidelines propose ≥ 3 years of HBV DNA undetectability to stop NA while others regard HBsAg loss as the only acceptable endpoint to therapy. Stopping NA can lead to substantial rates of virologic relapses and consequent ALT flares in some of them. Moreover, no reliable predictor(s) of post-NA relapses have been identified so far. Quantitative HBsAg is becoming an increasingly promising marker to predict safe NA cessation. On the other hand, investigating the role of the immune system in mediating sustained virologic responses after NA withdrawal is needed to suggest immunological biomarkers to safely stop NA. In this article, we will review relevant literature regarding NA stopping rules and discuss promising viral and immunological biomarkers to predict antiviral responses and thus to help identify patients who are more likely to achieve HBsAg seroclearance.

Keywords: HBV infection; NA discontinuation; Quantitative HBsAg; immune control; relapse.

Copyright © 2020. Published by Elsevier B.V.

StephenW

对慢性乙型肝炎患者停止核苷酸类似物治疗的看法
Issam Tout 1，Pietro Lampertico 2，Thomas Berg 3，Tarik Asselah 4
隶属关系
隶属关系

    1个
    巴黎迪德罗特大学，索邦巴黎市，CRI，UMR 1149，Inserm，F-75018巴黎，法国; AP-HPHôpitalBeaujon肝病科，法国克利希92110。
    2
    IRCCS Ca'Granda Ospedale Maggiore Policlinico基金会，CRC“ A。M.和A. Migliavacca”肝病中心胃肠病学和肝病学部门，意大利米兰；米兰大学，病理生理学和移植系，意大利米兰。
    3
    德国莱比锡莱比锡大学医学中心第二医学部肝病科。
    4
    巴黎迪德罗特大学，索邦巴黎市，CRI，UMR 1149，Inserm，F-75018巴黎，法国; AP-HPHôpitalBeaujon肝病科，法国克利希92110。电子地址：[email protected]。

    PMID：33279523 DOI：10.1016 / j.antiviral.2020.104992

抽象

当前大多数指南建议，使用核苷酸类似物（NAs）进行长期治疗是目前治疗慢性乙型肝炎（CHB）的一线治疗方法。 NAs可预防疾病进展，肝功能衰竭，降低肝细胞癌（HCC）的风险，并具有良好的安全性。但是，治疗中功能治愈率低（乙型肝炎表面抗原[HBsAg]丢失）被认为是最佳终点，这阻止了许多患者停止需要终身治疗的NA治疗。与持续的NAs相比，与停药相关的HBsAg丢失的可能性更高，最近引起了很多关注。在不同的国际指南中，关于允许安全停止NA治疗的终点的建议有所不同。在HBeAg阳性患者中，接受至少一年巩固治疗的HBeAg血清转化是公认的治疗终点，而对于HBeAg阴性的患者，建议却有所不同。一些指南建议≥3年无法检测到NA来终止NA，而另一些指南则认为HBsAg丢失是唯一可接受的治疗终点。停止NA可能会导致大量病毒学复发，并在其中一些中引起ALT发作。此外，到目前为止，尚未确定NA后复发的可靠预测因子。定量HBsAg正成为预测安全NA停用的越来越有希望的标志。另一方面，需要研究免疫系统在NA撤离后介导持续病毒学应答中的作用，以提示免疫学生物标记物可以安全地终止NA。在本文中，我们将回顾有关NA停止规则的相关文献，并讨论有希望的病毒和免疫生物标记物，以预测抗病毒反应，从而帮助确定更可能实现HBsAg血清清除的患者。

关键词：HBV感染； NA停产；定量HBsAg；免疫控制复发。

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