慢性HBV的功能性治疗的未来疗法：研究药物在第一和第二阶

StephenW

Current Hepatology Reports

December 2019, Volume 18, Issue 4, pp 503–511 | Cite as
Future Therapies for Functional Cure of Chronic HBV: Review of Investigational Drugs in Phase 1 and 2 Development

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    Lung-Yi MakWai-Kay SetoMan-Fung YuenEmail author

    Lung-Yi Mak
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    Wai-Kay Seto
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    Man-Fung Yuen
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    1.Department of MedicineQueen Mary HospitalHigh WestHong Kong
    2.Department of MedicineThe University of Hong KongPok Fu LamHong Kong
    3.State Key Laboratory of Liver ResearchThe University of Hong KongPok Fu LamHong Kong

Hepatitis B (J Lim, Section Editor)
First Online: 01 November 2019

   
Purpose of Review

Treating patients with chronic hepatitis B (CHB) infection with long-term oral antiviral therapy or pegylated interferon is the current standard of care (SOC). However, functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance that is associated with favorable clinical outcomes, is a rarely achieved treatment endpoint with the SOC.
Recent Findings

Remarkable advances in CHB therapy have been made in the recent years. This review was aimed to describe the different new treatment agents that are in the clinical phase of development. These include two main groups of agents that either target the viral replication cycle or enhance host immune control on the hepatitis B virus (HBV). The former group includes viral entry inhibitor, RNA gene silencers, core protein inhibitors, nucleic acid polymer, and monoclonal antibodies. The latter group includes toll-like receptor agonists, RIG-1/NOD2 agonist, therapeutic vaccines, and apoptosis inducer.
Summary

While some agents show promise in reduction of HBsAg levels and even HBsAg seroclearance, others are relatively modest in term of additional virological control effected by their different modes of action against HBV. These agents are in general well tolerated. Many upcoming new drugs against HBV are expected to enter phase II clinical trials. New challenge ahead would be the choice and duration of combination therapy to achieve a satisfactory rate of HBsAg seroclearance.
Keywords
Chronic hepatitis B virus Antiviral therapy Functional cure Hepatitis B surface antigen

StephenW

最新肝病报告

2019年12月，第18卷，第4期，第503–511页|引用为
慢性HBV的功能性治疗的未来疗法：研究药物在第一和第二阶段的发展回顾。

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1.香港西九龙玛丽医院
2.香港大学医学系薄扶林
3.香港大学肝脏研究国家重点实验室薄扶林

乙型肝炎（J Lim，栏目编辑）
首次在线：2019年11月1日


审查目的

长期口服抗病毒治疗或聚乙二醇干扰素治疗慢性乙型肝炎（CHB）感染患者是当前的护理标准（SOC）。但是，功能性治愈（定义为持续的乙型肝炎表面抗原（HBsAg）血清清除与良好的临床结果相关联）是SOC很少能达到的治疗终点。
最近的发现

近年来，CHB治疗取得了显着进展。这篇综述旨在描述处于临床开发阶段的不同新治疗剂。这些药物包括两大类药物，它们要么靶向病毒复制周期，要么增强对乙型肝炎病毒（HBV）的宿主免疫控制。前一组包括病毒进入抑制剂，RNA基因沉默子，核心蛋白抑制剂，核酸聚合物和单克隆抗体。后一组包括收费型受体激动剂，RIG-1 / NOD2激动剂，治疗性疫苗和凋亡诱导剂。
摘要

尽管某些药物有望降低HBsAg水平，甚至降低HBsAg血清清除率，但其他药物在针对HBV的不同作用方式所带来的额外病毒学控制方面相对适中。这些试剂通常被很好地耐受。预计许多即将出现的抗HBV新药将进入II期临床试验。未来的新挑战将是联合治疗的选择和持续时间，以达到令人满意的HBsAg血清清除率。
关键词
慢性乙型肝炎病毒抗病毒治疗功能治愈乙型肝炎表面抗原