乙型肝炎表面抗原血清清除：免疫机制，临床影响，药物开

StephenW

J Hepatol. 2020 Apr 22. pii: S0168-8278(20)30225-7. doi: 10.1016/j.jhep.2020.04.013. [Epub ahead of print]
Hepatitis B Surface Antigen Seroclearance: Immune Mechanisms, Clinical Impact, Importance for Drug Development.
Tout I1, Loureiro D1, Mansouri A1, Soumelis V2, Boyer N1, Asselah T3.
Author information

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
    Institut Curie, Centre de Recherche, PSL Research University, Paris, France; INSERM U932, Immunity and Cancer, Paris, France.
3
    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].

Abstract

Hepatitis B surface antigen (HBsAg) seroclearance occurs rarely in the natural history of chronic hepatitis B (CHB) infection and is associated with a reduced risk of hepatocellular carcinoma (HCC). Many factors are associated with HBsAg seroconversion, including immune, and viral factors. However, the immune mechanisms associated with HBsAg seroclearance are still difficult to elucidate. The aim of the treatment of hepatitis B virus (HBV) infection is the seroclearance of HBsAg. Unfortunately, this goal is rarely reached with current approved treatments. Understanding HBsAg loss mechanisms appears important to achieve an HBV cure drug development. While studies from HBV animal models are giving insights on the potential immune mechanisms and interactions occurring between the immune system and HBsAg, they do not recapitulate all features of CHB in human and are subject to variability due to their complexity. In this article, we review recent studies on these immune factors, their influence on CHB progression, and HBsAg seroconversion. These data provide new insights in the development of immune therapeutic approaches to partially restore the anti-HBV immune response. Targeting HBsAg will ideally relieve the immunosuppressive effects on the immune system and help to restore anti-HBV immune responses.

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KEYWORDS:

Chronic HBV infection; HBV therapy; HBsAg seroclearance; Immune system; Interferon; Nucleos(t)ide analogues

PMID:
    32333923
DOI:
    10.1016/j.jhep.2020.04.013

StephenW

J肝素。 2020年4月22日。pii：S0168-8278（20）30225-7。 doi：10.1016 / j.jhep.2020.04.013。 [Epub提前发行]
乙型肝炎表面抗原血清清除：免疫机制，临床影响，药物开发的重要性。
Tout I1，Loureiro D1，Mansouri A1，Soumelis V2，Boyer N1，Asselah T3。
作者信息

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
    法国巴黎PSL研究大学Recherche中心居里研究所； INSERM U932，《免疫与癌症》，法国巴黎。
3
    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]。

抽象

乙型肝炎表面抗原（HBsAg）的血清清除在慢性乙型肝炎（CHB）感染的自然史中很少发生，并且与降低的肝细胞癌（HCC）风险有关。 HBsAg血清转化与许多因素有关，包括免疫和病毒因素。但是，与HBsAg血清清除相关的免疫机制仍然难以阐明。治疗乙型肝炎病毒（HBV）感染的目的是清除HBsAg的血清。不幸的是，目前批准的治疗方法很少达到这个目标。了解HBsAg的丢失机制对于实现HBV治愈药物的开发似乎很重要。尽管来自HBV动物模型的研究提供了有关潜在的免疫机制以及免疫系统与HBsAg之间发生相互作用的见解，但它们并未概括人类CHB的所有特征，并且由于其复杂性而易变。在本文中，我们回顾了有关这些免疫因子，它们对CHB进展和HBsAg血清转化的影响的最新研究。这些数据为免疫治疗方法的发展提供了新的见解，以部分恢复抗-HBV免疫反应。靶向HBsAg将理想地减轻对免疫系统的免疫抑制作用，并有助于恢复抗HBV免疫反应。

版权所有©2020欧洲肝病研究协会。由Elsevier B.V.发布。保留所有权利。
关键字：

慢性HBV感染；乙肝病毒治疗； HBsAg血清清除；免疫系统;干扰素核苷类似物

PMID：
    32333923
DOI：
    10.1016 / j.jhep.2020.04.013