评论文章 对慢性乙型肝炎的新疗法

StephenW

Review Article

New therapies for chronic hepatitis B

    Maya Bitton Alaluf1 andAmir Shlomai1,2,3,*

Article first published online: 14 MAR 2016

DOI: 10.1111/liv.13086

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Issue
Liver International

Volume 36, Issue 6, pages 775–782, June 2016
Article has an altmetric score of 1



    1    Department of Medicine D, Beilinson Hospital Rabin Medical Center, Petah Tikva, Israel
    2    The Liver Institute, Beilinson Hospital Rabin Medical Center, Petah Tikva, Israel
    3    The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

* Correspondence
Amir Shlomai, MD, PhD, Department of Medicine D, Beilinson Hospital Rabin Medical Center, 39 Jabotinski Street, 49100 Petah-Tikva, Israel
Tel: +972 3 9376751/3; Fax: +972 9220671
e-mail: [email protected]

    Handling editor: Mario Mondelli



Abstract

Approximately 350 million people worldwide are chronically infected with hepatitis B virus (HBV), representing a significant public health challenge. Nucleos/tide analogues (NUCs) and interferon alpha (IFNα), the current standard of care for chronic infection, aim at preventing progression of the disease to cirrhosis, hepatocellular carcinoma (HCC) and death. However, in contrast to the case of hepatitis C virus infection, in which novel antiviral drugs cure the vast majority of treated patients, in regard to HBV, cure is rare due to the unusual persistence of viral DNA in the form of covalently closed circular DNA (cccDNA) within the nucleus of infected cells. Available therapies for HBV require lifelong treatment and surveillance, as reactivation frequently occurs following medication cessation and the occurrence of HCC is decreased but not eliminated, even after years of successful viral suppression. Progress has been made in the development of new therapeutics, and it is likely that only a combination of immune modulators, inhibitors of gene expression and replication and cccDNA-targeting drugs will eradicate chronic infection. This review aims to summarize the state of the art in HBV drug research highlighting those agents with the greatest potential for success based on in vitro as well as on data from clinical studies.

StephenW

评论文章

对慢性乙型肝炎的新疗法

    玛雅比顿Alaluf1 andAmir Shlomai1,2,3，*

文章首次在线发表时间：2016年3月14日

DOI：10.1111 / liv.13086

2016年©约翰·威利父子A / S。由John Wiley＆Sons出版有限公司

问题
肝国际

第36卷，第6期，页775-782，2016年6月
文章为1的比分altmetric



    医药研发，贝林松医院拉宾医学中心，佩塔提克瓦，以色列1系
    2肝脏研究所贝林松医院拉宾医学中心，佩塔提克瓦，以色列
    3医药的赛克勒学院，特拉维夫大学，特拉维夫，以色列

*通讯
阿米尔Shlomai，博士，医药研发，贝林松医院拉宾医学中心，39 Jabotinski街系，49100佩塔提克瓦-Tikva的，以色列
电话：+972 33分之9376751;传真：+972 9220671
电子邮件：[email protected]

    处理编辑：马里奥Mondelli



抽象

全世界约有3.5亿人为慢性感染乙型肝炎病毒（HBV），较显著的公共卫生挑战。核苷/潮类似物（NUCs）和干扰素α（IFNα），护理的当前标准慢性感染，旨在防止疾病的发展成肝硬化，肝细胞癌（HCC）和死亡。然而，与此相反的丙型肝炎病毒感染的情况下，在这种新颖的抗病毒药物治疗绝大多数治疗的患者的，关于HBV，治愈是罕见的，由于病毒DNA在共价闭合环状DNA的形式的不寻常的持久性（cccDNA的）感染的细胞的细胞核内。乙肝的治疗提供需要终身治疗和监测，为激活经常出现以下停止用药和HCC的发生减少，但并没有消除，即使经过多年成功的病毒抑制。进展的新疗法的发展而提出的，并且很可能只有一个免疫调节剂的组合，基因表达和复制和cccDNA的靶向药物的抑制剂将根除慢性感染。这次审查的目的总结的技术HBV药物的研究突出了这些代理与基于体外以及对临床研究数据的成功潜力最大的国家。

StephenW

Conclusions and future perspectives

The advent of new antiviral therapy against HCV infection, which has been shown to remedy most cases of chronic HCV, has brought about a plethora of enthusiasm in duplicating the success in HBV therapeutics.

In this review, we aim to briefly summarize the future therapeutics for HBV while schematically dividing them into three elements – those directed at specific steps in viral life cycle and spread, those aimed at augmenting and restoring the host immune responses and those specifically targeting cccDNA.

Although most agents showed great promise in vitro, data from clinical trials seem to be mostly premature at this point. It is likely that an integrative antiviral approach combining components of these elements will be needed to surmount CHB infection (Fig. 1). Clearly, the subsequent steps of clinical trials will be fascinating to follow, but the intense efforts done in the field hold promise that cure for this long-standing, debilitating and sometimes fatal disease, is already within our reach.
image

Figure 1. Integration of therapeutic strategies to better control HBV infection. Current efforts to develop innovative strategies to better control HBV are divided into three interdependent arms that complement and synergize each other: Interference with viral life cycle and spread, immune modulation and directly targeting cccDNA. The elimination of cccDNA is the ultimate goal in future therapy and is a perquisite for viral eradication and cure.

结论和前景

的抗HCV感染，这已被证明是补救慢性HCV的大多数情况下，新的抗病毒疗法的出现，带来了的热情在复制中的HBV治疗的成功过多。

在这次审查中，我们的目标是简单地概括为HBV未来的治疗，同时示意划分成三个要素 - 那些针对病毒的生命周期和扩散的具体措施，是旨在充实和恢复宿主免疫反应和那些专门针对cccDNA的。

尽管大多数机构表现出体外很大的希望，从临床试验的数据似乎在这一点上大多是不成熟的。它很可能是这些元素的成分的综合抗病毒的方法，将需要克服CHB感染（图1）。显然，临床试验的后续步骤将是有趣的跟随，但在治愈这种长期存在的领域保持承诺所做的巨大努力，衰弱，有时甚至是致命的疾病，已经是我们力所能及的。
图片

图1.治疗策略整合，以更好地控制乙肝病毒感染。目前努力发展创新战略，以更好地控制乙肝病毒被分成互补和协同对方三个相互武器：干扰病毒的生命周期和扩散，免疫调节和直接针对cccDNA的。 cccDNA的消除是未来治疗的最终目标，是为消灭病毒和固化一个油水。

StephenW

全文:
http://onlinelibrary.wiley.com/doi/10.1111/liv.13086/full