慢性乙型肝炎病毒学，自然历史，目前的管理和一瞥未来的

StephenW

Antiviral Res. 2015 Jun 16. pii: S0166-3542(15)00139-4. doi: 10.1016/j.antiviral.2015.06.008. [Epub ahead of print]
Chronic hepatitis B: virology, natural history, current management and a glimpse at future opportunities.Gish RG1, Given BD2, Lai CL3, Locarnini SA4, Lau JY5, Lewis DL2, Schluep T2.
Author information

• 1Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Stanford, California, USA. Electronic address: [email protected].
• 2Arrowhead Research Corporation, Pasadena, California, USA.
• 3The University of Hong Kong, Hong Kong, China.
• 4Victorian Infectious Diseases Reference Laboratory, Victoria, Australia.
• 5Hong Kong Polytechnic University, Hong Kong, China.
  

AbstractThe host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the "high replicative, low inflammatory" phase now replacing what was formerly termed the "immune tolerant" phase, and the "nonreplicative phase" replacing what was formerly termed the "inactive carrier" phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate's immune system, new findings on trained immunity show that the host is already somewhat "matured" following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of 'cure' are emerging, such as 'functional' and 'virological' cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."
Copyright © 2015. Published by Elsevier B.V.


KEYWORDS: Antiviral therapy; Functional cure; Hepatitis B virus; Phases of infection; Trained immunity; Virological cure

StephenW

抗病毒水库。 2015年16月PII：S0166-3542（15）00139-4。 DOI：10.1016 / j.antiviral.2015.06.008。 [打印EPUB的提前]
慢性乙型肝炎病毒学，自然历史，目前的管理和一瞥未来的机遇。
吉什RG1，鉴于BD2，赖CL3，Locarnini SA4，刘JY5，刘易斯DL2，Schluep先生T2。
作者信息

    1区学和免疫，医学系，斯坦福大学医学中心，斯坦福大学，美国加利福尼亚州。电子地址：[email protected]。
    2Arrowhead研究公司，帕萨迪纳，美国加利福尼亚州。
    香港，香港，中国的大学3The。
    4Victorian传染病参考实验室，澳大利亚维多利亚州。
    5Hong香港理工大学，香港，中国。

抽象

宿主的免疫系统在慢性乙型肝炎（CHB）中起重要作用，无论是在病毒清除和肝细胞损伤。在我们的疾病的自然史的认识的不断深入，导致重新定义感染的主要阶段，与“高复制性，炎症性低”阶段，现在更换了什么以前称为“免疫耐受”阶段，而“非复制性阶段”替换什么以前称为“惰性载体”阶段。相对于早期的观点，即乙肝病毒通过利用新生儿的免疫系统不成熟建立慢性感染，对经过培训的免疫力展示新发现的主机已经有点“成熟”之后诞生，其实是非常有能力应对免疫，有可能改变的今后乙肝治疗策略。而现有的疗法可有效减少病毒载量和坏死性炎症，经常恢复患者接近正常健康，他们不停止治疗后导致的固化，除了在极少数情况下，并且在许多患者中，病毒血症篮板。研究人员现在面临的挑战是制定疗法，将消除感染，尤其侧重于消除肝细胞的细胞核病毒的cccDNA的持久性。在慢性乙型肝炎的上下文中，“固化”的新的定义正在出现，如“功能性”和“病毒学”治愈，通过稳定截止疗法抑制病毒血症和抗原的定义，且血清ALT和其它liver-正常化相关的实验室检查。在慢性乙型肝炎的复杂生物学的理解持续进步已导致靶向病毒和宿主因素与途径先前没有接触到治疗新，实验性疗法的发展，接近可能导致病毒学固化在短期和官能固化在长期的随访。本文形成在抗病毒研究的专题讨论会的一部分，“一个未完成的故事：从澳大利亚抗原的发现到新的治疗疗法的发展为乙型肝炎”

版权所有©2015年出版由Elsevier B.V.
关键词：

抗病毒治疗;功能治愈;乙型肝炎病毒;感染的阶段;训练有素的免疫力;病毒学治愈