治疗慢性乙型肝炎的新方法

StephenW

New Approaches to the Treatment of Chronic Hepatitis B
Alexandra Alexopoulou  1 , Larisa Vasilieva  1 , Peter Karayiannis  2
Affiliations
Affiliations

    1
    Department of Medicine, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, 11527 Athens, Greece.
    2
    Department of Basic and Clinical Sciences, Medical School, University of Nicosia, Engomi, CY-1700 Nicosia, Cyprus.

    PMID: 33019573 DOI: 10.3390/jcm9103187

Abstract

The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg loss, inhibition of new hepatocyte infection, elimination of the covalently closed circular DNA (cccDNA) pool, and restoration of immune function in order to achieve virus control. This review concentrates on new antiviral drugs that target different stages of the HBV life cycle (direct acting antivirals) and others that enhance both innate and adaptive immunity against HBV (immunotherapy). Drugs that block HBV hepatocyte entry, compounds that silence or deplete the cccDNA pool, others that affect core assembly, agents that degrade RNase-H, interfering RNA molecules, and nucleic acid polymers are likely interventions in the viral life cycle. In the immunotherapy category, molecules that activate the innate immune response such as Toll-like-receptors, Retinoic acid Inducible Gene-1 (RIG-1) and stimulator of interferon genes (STING) agonists or checkpoint inhibitors, and modulation of the adaptive immunity by therapeutic vaccines, vector-based vaccines, or adoptive transfer of genetically-engineered T cells aim towards the restoration of T cell function. Future therapeutic trends would likely be a combination of one or more of the aforementioned drugs that target the viral life cycle and at least one immunomodulator.

Keywords: DNA vaccines; capsid inhibitors; cccDNA modifiers; chronic hepatitis B; direct acting antivirals; hepatitis B virus; immunotherapy; siRNA.
Publication types

    Review

StephenW

治疗慢性乙型肝炎的新方法
亚历山德拉·亚历克索普洛1，拉里莎·瓦西里耶娃1，彼得·卡拉扬尼斯2
隶属关系
隶属关系

    1个
    雅典国立与卡波迪斯安大学医学院医学系，希腊希波拉奇综合医院，希腊11527。
    2
    尼科西亚大学医学院基础和临床科学系，恩戈米，CY-1700，塞浦路斯尼科西亚。

    PMID：33019573 DOI：10.3390 / jcm9103187

抽象

当前推荐的治疗慢性乙型肝炎病毒（HBV）的方法只能在治疗时实现病毒抑制，但很少会损失乙型肝炎表面抗原（HBsAg）。最终的治疗终点是HBsAg丢失，抑制新的肝细胞感染，消除共价闭合的环状DNA（cccDNA）库以及恢复免疫功能以实现病毒控制的结合。这篇综述集中在针对HBV生命周期不同阶段的新抗病毒药物（直接作用抗病毒药）以及其他增强针对HBV的固有和适应性免疫（免疫疗法）的药物。阻断HBV肝细胞进入的药物，沉默或耗尽cccDNA库的化合物，影响核心组装的其他药物，降解RNase-H的药物，干扰RNA分子和核酸聚合物的药物都可能是病毒生​​命周期的干预手段。在免疫疗法类别中，激活先天免疫应答的分子，例如Toll样受体，视黄酸诱导基因-1（RIG-1）和干扰素基因激动剂（STING）激动剂或检查点抑制剂，以及适应性免疫的调节通过治疗性疫苗，基于载体的疫苗或基因工程T细胞的过继转移，旨在恢复T细胞的功能。未来的治疗趋势可能是一种或多种针对病毒生命周期的上述药物与至少一种免疫调节剂的组合。

关键词：DNA疫苗；衣壳抑制剂； cccDNA修饰子;慢性乙型肝炎直接作用抗病毒药；乙型肝炎病毒;免疫疗法siRNA。
出版类型

    评论

newchinabok

未来的治疗趋势可能是一种或多种针对病毒生命周期的上述药物与至少一种免疫调节剂的组合。

newchinabok

免疫药都不成功