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肝胆相照论坛 论坛 学术讨论& HBV English 乙型肝炎表面抗原血清清除:免疫机制,临床影响,药物开 ...
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乙型肝炎表面抗原血清清除:免疫机制,临床影响,药物开 [复制链接]

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发表于 2020-6-13 20:19 |只看该作者 |倒序浏览 |打印
Hepatitis B Surface Antigen Seroclearance: Immune Mechanisms, Clinical Impact, Importance for Drug Development

    Issam Tout
    Dimitri Loureiro
    Abdellah Mansouri
    Vassili Soumelis
    Nathalie Boyer
    Tarik Asselah

Published:April 22, 2020DOI:https://doi.org/10.1016/j.jhep.2020.04.013
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    Introduction
    Conclusion
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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.
Keywords

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

Abbreviations:
aa (amino acid), ALT (Alanine aminotransferase), anti-HBsAg (hepatitis B surface antigen antibodies), AST (Aspartate aminotransferase), AIM2 (Absent in melanoma 2), atMBC (Atypic Memory B cells), cccDNA (covalently closed circular DNA), CHB (chronic hepatitis B), CTL (Cytotoxic T cell), DC (Dendritic cells), ETV (entecavir), FDA (Food and Drug Administration), FNA (Fine needle aspiration), HBcAg (Hepatitis B core antigen), HBcrAg (Hepatitis B core-related antigen), HBeAg (Hepatitis B e antigen), HBsAg (Hepatitis B surface antigen), HBV (hepatitis B virus), HBV SVPs (Hepatitis B virus sub-viral particles), HCC (hepatocellular carcinoma), hNTCP (human sodium taurocholate cotransporting polypeptide), IFN-α (interferon alpha), IL (Interleukin), IRF7 (Interferon regulatory factor 7), JNK (c-Jun N-terminal protein kinase), KC (Kupffer cells), LAG-3 (Lymphocyte-activation gene 3), L-HBsAg (Large Hepatitis B surface antigen), LSEC (Liver sinusoidal endothelial cells), MAIT (mucosal associated invariant T cells), MDSC (Myeloid-derived suppressor cells), M-HBsAg (Medium Hepatitis B surface antigen), mRNA (messenger RNA), MVP (Major vault protein), MyD88 (Myeloid differentiation primary response 88), NA (nucleoside analogue), NAP (Nucleic Acid Polymer), NK cells (Natural Killer cells), ORF (open reading frames), PD-1 (Programmed cell death protein 1), PEG-IFN (pegylated interferon), pgRNA (pregenomic RNA), PRR (Pattern recognition receptor), rcDNA (relaxed circular DNA), S-HBsAg (Small Hepatitis B surface antigen), siRNA (small interfering RNA), TAF (tenofovir alafenamide), T-bet (T-box protein expressed in T cells), TDF (tenofovir disoproxil fumarate), TFH (T Follicular Helper cell), TFV (tenofovir), Tim-3 (T-cell immunoglobulin and mucin-domain containing-3), TLR (toll-like receptor), TNF-α (Tumor necrosis factor alpha), Treg (Regulatory T cells)
Key Points

    -
    HBsAg seroclearance is a rare event in the natural history of CHB.
    -
    HBsAg seroclearance is associated with a reduced risk of HCC.
    -
    HBsAg contributes to the deregulation of both innate and adaptive immune cells.
    -
    The decrease of HBsAg can potentially restore anti-HBV immune responses.
    -
    Combination of antivirals and immune therapy is crucial for drug development.

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发表于 2020-6-13 20:19 |只看该作者
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。

    伊萨姆·图特(Issam Tout)
    迪米特里·洛雷罗(Dimitri Loureiro)
    阿卜杜拉·曼苏里(Abdellah Mansouri)
    瓦西里·苏梅利斯(Vassili Soumelis)
    娜塔莉·博耶(Nathalie Boyer)
    塔里克·阿瑟拉(Tarik Asselah)

发布时间:2020年4月22日DOI:https://doi.org/10.1016/j.jhep.2020.04.013
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抽象
乙型肝炎表面抗原(HBsAg)的血清清除很少发生在慢性乙型肝炎(CHB)感染的自然史中,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。
关键词

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

缩略语:
aa(氨基酸),ALT(丙氨酸转氨酶),抗HBsAg(乙型肝炎表面抗原抗体),AST(天冬氨酸转氨酶),AIM2(黑色素瘤2缺失),atMBC(非典型记忆B细胞),cccDNA(共价闭合圆DNA),CHB(慢性乙型肝炎),CTL(细胞毒性T细胞),DC(树突状细胞),ETV(恩替卡韦),FDA(食品和药物管理局),FNA(细针穿刺),HBcAg(乙肝核心抗原) ,HBcrAg(乙型肝炎核心相关抗原),HBeAg(乙型肝炎e抗原),HBsAg(乙型肝炎表面抗原),HBV(乙型肝炎病毒),HBV SVP(乙型肝炎病毒亚病毒颗粒),HCC(肝细胞癌) ),hNTCP(人牛磺胆酸钠共转运多肽),IFN-α(干扰素α),IL(白介素),IRF7(干扰素调节因子7),JNK(c-Jun N末端蛋白激酶),KC(库普弗细胞), LAG-3(淋巴细胞激活基因3),L-HBsAg(大乙型肝炎表面抗原),LSEC(肝窦窦内皮细胞),MAIT(粘膜相关不变T细胞),MDSC(淀粉样来源的抑制细胞),M-HBsAg(乙型肝炎表面抗原),mRNA(信使RNA),MVP(主要穹protein蛋白),MyD88(淀粉样分化主要反应88),NA(核苷)类似物),NAP(核酸聚合物),NK细胞(自然杀伤细胞),ORF(开放阅读框),PD-1(程序性细胞死亡蛋白1),PEG-IFN(聚乙二醇化干扰素),pgRNA(前基因组RNA), PRR(模式识别受体),rcDNA(松弛的环状DNA),S-HBsAg(小乙型肝炎表面抗原),siRNA(小干扰RNA),TAF(替诺福韦阿拉芬酰胺),T-bet(在T细胞中表达的T-box蛋白) ),TDF(替诺福韦富马酸替诺福韦),TFH(T卵泡辅助细胞),TFV(替诺福韦),Tim-3(T细胞免疫球蛋白和含有粘蛋白结构域的-3),TLR(收费类受体),TNF-α (肿瘤坏死因子α),Treg(调节性T细胞)
关键点

    --
    HBsAg血清清除是CHB自然病史中罕见的事件。
    --
    HBsAg血清清除与降低HCC风险有关。
    --
    HBsAg有助于先天性和适应性免疫细胞的失调。
    --
    HBsAg的减少可能会恢复抗HBV免疫反应。
    --
    抗病毒药物和免疫疗法的结合对于药物开发至关重要。

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才高八斗

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发表于 2020-6-13 20:19 |只看该作者
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