核心/衣壳抑制剂在慢性乙型肝炎功能治愈策略中的作用

StephenW

Role of Core/Capsid Inhibitors in Functional Cure Strategies for Chronic Hepatitis B

    Rex Wan-Hin Hui, Lung-Yi Mak, Wai-Kay Seto & Man-Fung Yuen

Current Hepatology Reports volume 19, pages293–301(2020)Cite this article

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Abstract
Purpose of Review

Functional cure of chronic hepatitis B (CHB), defined as sustained hepatitis B surface antigen (HBsAg) seroclearance, is associated with favourable clinical outcomes. Nonetheless, the functional cure is rarely achievable by current treatment modalities. Core/capsid inhibitors (core protein allosteric modulators, CpAMs) are a novel drug class that targets the hepatitis B core protein and may have a potential impact on the functional cure. This article reviews the preclinical and clinical results of CpAMs.
Recent Findings

CpAMs interfere with the hepatitis B virus (HBV) nucleocapsid assembly and also exert a secondary action on covalently closed circular DNA replenishment. CpAMs are able to sustainably suppress hepatitis B viral load and viral antigens in in vivo studies. In phase I/II clinical trials, CpAMs are well tolerated and are efficacious in suppressing viral replication. CpAMs also have synergistic antiviral effects when combined with nucleoside analogues or pegylated interferon. The clinical data has yet to demonstrate the capability of CpAMs in inducing HBsAg seroclearance, possibly due to the short follow-up period of current studies. There is emerging data showing initial viral antigen reduction with the continuation of CpAMs for more than 24 weeks.
Summary

CpAMs have shown promising preclinical and phase I/II clinical data. Data from long-term phase III trials and from combination therapies with other antiviral agents are keenly anticipated.

StephenW

核心/衣壳抑制剂在慢性乙型肝炎功能治愈策略中的作用

    许婉轩，麦龙怡，濑户威及袁文峰

《当前肝病学报告》第19卷，第293–301页（2020年）

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抽象
审查目的

慢性乙型肝炎（CHB）的功能性治疗定义为持续的乙型肝炎表面抗原（HBsAg）血清清除，与良好的临床疗效相关。尽管如此，目前的治疗方法很少能实现功能性治疗。核心/衣壳抑制剂（核心蛋白变构调节剂，CpAMs）是针对乙型肝炎核心蛋白的新型药物，可能会对功能治愈产生潜在影响。本文回顾了CpAM的临床前和临床结果。
最近的发现

CpAM会干扰乙型肝炎病毒（HBV）的核衣壳装配，并在共价闭合的环状DNA补充中发挥次要作用。在体内研究中，CpAM能够持续抑制乙型肝炎病毒载量和病毒抗原。在I / II期临床试验中，CpAM具有良好的耐受性，可有效抑制病毒复制。当与核苷类似物或聚乙二醇化干扰素联合使用时，CpAM还具有协同抗病毒作用。临床数据尚未证明CpAMs诱导HBsAg血清清除的能力，可能是由于目前研究的随访时间较短。新出现的数据显示，随着CpAM持续24周以上，病毒抗原的初始减少。
摘要

CpAM已显示出有希望的临床前和I / II期临床数据。迫切期望获得长期的III期临床试验数据以及与其他抗病毒药物联合治疗的数据。

newchinabok

临床数据尚未证明CpAMs诱导HBsAg血清清除的能力，可能是由于目前研究的随访时间较短。新出现的数据显示，随着CpAM持续24周以上，病毒抗原的初始减少。

newchinabok

abi—h0731长期试验数据就可以看看降hbsag效果

windu

核衣壳短期没有看到表面抗原的降低，长期能看到降低，证明它的理论就是正确的