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慢性乙型肝炎治疗的新方法

New Approaches to the Treatment of Chronic Hepatitis B.

作者信息

Alexopoulou Alexandra, Vasilieva Larisa, Karayiannis Peter

机构信息

Department of Medicine, Medical School, National & Kapodistrian University of Athens, Hippokration General Hospital, 11527 Athens, Greece.

Department of Basic and Clinical Sciences, Medical School, University of Nicosia, Engomi, CY-1700 Nicosia, Cyprus.

出版信息

J Clin Med. 2020 Oct 1;9(10):3187. 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.

摘要

目前推荐的慢性乙型肝炎病毒(HBV)感染治疗方法仅在治疗期间实现病毒抑制,但很少能使乙肝表面抗原(HBsAg)消失。最终的治疗终点是HBsAg消失、抑制新的肝细胞感染、消除共价闭合环状DNA(cccDNA)库以及恢复免疫功能以实现病毒控制。本综述着重介绍针对HBV生命周期不同阶段的新型抗病毒药物(直接作用抗病毒药物)以及其他增强针对HBV的固有免疫和适应性免疫的药物(免疫疗法)。阻断HBV进入肝细胞的药物、使cccDNA库沉默或清除的化合物、影响核心组装的其他药物、降解核糖核酸酶H的药物、干扰RNA分子以及核酸聚合物可能是对病毒生命周期的干预措施。在免疫疗法类别中,激活固有免疫反应的分子,如Toll样受体、视黄酸诱导基因-1(RIG-1)和干扰素基因刺激物(STING)激动剂或检查点抑制剂,以及通过治疗性疫苗、基于载体的疫苗或基因工程T细胞的过继转移来调节适应性免疫,旨在恢复T细胞功能。未来的治疗趋势可能是将上述一种或多种针对病毒生命周期的药物与至少一种免疫调节剂联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631f/7601587/c770f5ed5e9c/jcm-09-03187-g001.jpg

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