[丙型肝炎能治好吗乙型肝炎会成为下一个吗？]

StephenW

Ter Arkh. 2017;89(11):4-13. doi: 10.17116/terarkh201789114-13.
[Hepatitis C can be cured: will hepatitis B become next?] [Article in Russian;  Abstract available in Russian from the publisher]
Chulanov VP1, Zueva AP2, Kostyushev DS3, Brezgin SA3, Volchkova EV4, Maleyev VV3.
Author information
1Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation, Moscow, Russia.2Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia; M.V. Lomonosov Moscow State University, Moscow, Russia.3Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia.4I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation, Moscow, Russia.

Abstractin                                English, Russian
Chronic hepatitis B (CHB) and C (CHC) are one of the leading causes of cirrhosis and liver cancer with over a million of people dying annually from their consequences. In Russia CHB and CHC morbidity and related mortality show an upward trend. As a result of recent breakthroughs in antiviral therapeutics CHC became a curable disease. Modern therapeutics effectively suppress viral replication in CHB patients, but withdrawal of antivirals usually results in disease relapse. Loss of HBsAg required for the so called 'functional cure' is a very rare event. Moreover, 'complete cure' when the virus is entirely eliminated from the body is not possible due to a persistent form of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes refractory to modern antivirals. Today, there is a plethora of new promising medications being at different stages of development that target different steps of viral life cycle, including inhibitors of interaction between HBV and its entry receptor NTCP, inhibitors of HBV cccDNA, inhibitors of nucleocapsid assembly, technologies of genome editing (TALENs, CRISPR/Cas etc) and RNA-interference. In addition to direct acting antivirals, there is a number of approaches aimed at enhancement of the innate and adaptive immune responses. In experimental conditions, some of these approaches or their combinations help to achieve functional cure. However, complete elimination of the virus is possible only using technologies of genome editing, capable of specific cccDNA degradation. Nuclease systems are currently at their early stages of development, and there is a long way to prove their efficacy and safety. Nevertheless, highly promising results of the recent years leave no doubt that CRISPR/Cas systems and similar technologies can become the basis of CHB therapy.


KEYWORDS: CRISPR/Cas9; chronic hepatitis B; covalently closed circular DNA; gene therapy; hepatitis B virus; immunotherapy; miRNA; molecular therapy

PMID:29260740DOI:10.17116/terarkh201789114-13

StephenW

Ter Arkh。 2017; 89（11）：4-13。 doi：10.17116 / terarkh201789114-13。
[丙型肝炎能治好吗乙型肝炎会成为下一个吗？]
[俄语文章;摘要在俄罗斯提供从出版商]
Chulanov VP1，Zueva AP2，Kostyushev DS3，Brezgin SA3，Volchkova EV4，Maleyev VV3。
作者信息

1
    俄罗斯莫斯科Rospotrebnadzor流行病学中心研究所;俄罗斯莫斯科俄罗斯联邦卫生部第一莫斯科国立医科大学。
2
    俄罗斯莫斯科Rospotrebnadzor流行病学中心研究所; M.V.俄罗斯莫斯科罗蒙诺索夫莫斯科国立大学。
3
    俄罗斯莫斯科Rospotrebnadzor流行病学中心研究所。
4
    俄罗斯莫斯科俄罗斯联邦卫生部第一莫斯科国立医科大学。

摘要英文，俄文

慢性乙型肝炎（CHB）和C（CHC）是肝硬化和肝癌的主要原因之一，每年有超过一百万人死于肝炎。在俄罗斯，CHB和CHC发病率及相关死亡率呈上升趋势。由于近期在抗病毒治疗方面的突破，CHC成为一种可治愈的疾病。现代疗法有效地抑制CHB患者中的病毒复制，但是抗病毒剂的停用通常导致疾病复发。所谓“功能性治愈”所需的HBsAg的丢失是非常罕见的事件。此外，当病毒完全从体内消除时，“完全治愈”是不可能的，因为在现代抗病毒药物难治的肝细胞中存在乙型肝炎病毒（HBV）的共价闭合环状DNA（cccDNA）的持续形式。今天，有许多新的有前景的药物处于不同的发展阶段，针对病毒生命周期的不同阶段，包括HBV与其进入受体NTCP之间相互作用的抑制剂，HBV cccDNA抑制剂，核衣壳组装抑制剂，基因组技术编辑（TALENs，CRISPR / Cas等）和RNA干扰。除了直接作用的抗病毒剂之外，还有许多旨在增强先天和适应性免疫应答的方法。在实验条件下，这些方法中的一些或其组合有助于实现功能治愈。但是，只有使用基因组编辑技术才能完全消除病毒，这种技术能够特异性降解cccDNA。核酸酶系统目前处于发展的早期阶段，证明其有效性和安全性还有很长的路要走。尽管如此，近年来非常有希望的结果使CRISPR / Cas系统和类似技术成为CHB治疗的基础。
关键词：

CRISPR / Cas9;慢性乙型肝炎;共价闭合的环状DNA;基因治疗;乙肝病毒;免疫治疗; miRNA的;分子疗法

结论：
    29260740
DOI：
    10.17116 / terarkh201789114-13