靶向病毒cccDNA治愈慢性乙型肝炎

StephenW

Targeting Viral cccDNA for Cure of Chronic Hepatitis B

    Gaëtan Ligat, Kaku Goto, Eloi Verrier & Thomas F. Baumert

Current Hepatology Reports volume 19, pages235–244(2020)Cite this article

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Abstract
Purpose of Review

Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a major cause of advanced liver disease and hepatocellular carcinoma (HCC) worldwide. HBV replication is characterized by the synthesis of covalently closed circular (ccc) DNA which is not targeted by antiviral nucleos(t)ide analogues (NUCs) the key modality of standard of care. While HBV replication is successfully suppressed in treated patients, they remain at risk for developing HCC. While functional cure, characterized by loss of HBsAg, is the first goal of novel antiviral therapies, curative treatments eliminating cccDNA remain the ultimate goal. This review summarizes recent advances in the discovery and development of novel therapeutic strategies and their impact on cccDNA biology.
Recent Findings

Within the last decade, substantial progress has been made in the understanding of cccDNA biology including the discovery of host dependency factors, epigenetic regulation of cccDNA transcription and immune-mediated degradation. Several approaches targeting cccDNA either in a direct or indirect manner are currently at the stage of discovery, preclinical or early clinical development. Examples include genome-editing approaches, strategies targeting host dependency factors or epigenetic gene regulation, nucleocapsid modulators and immune-mediated degradation.
Summary

While direct-targeting cccDNA strategies are still largely at the preclinical stage of development, capsid assembly modulators and immune-based approaches have reached the clinical phase. Clinical trials are ongoing to assess their efficacy and safety in patients including their impact on viral cccDNA. Combination therapies provide additional opportunities to overcome current limitations of individual approaches.

StephenW

扩增病毒cccDNA治愈慢性乙型肝炎

    GaëtanLigat，Kaku Goto，Eloi Verrier和Thomas F.Baumert

《当前肝病学报告》第19卷，第235-244页（2020年）

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抽象
审查目的

由乙型肝炎病毒（HBV）引起的慢性乙型肝炎（CHB）是全球晚期肝病和肝细胞癌（HCC）的首要。乙肝病毒复制的特征是合成共价封闭的DNA（ccc），而抗病毒的核苷酸（t）ide类似物（NUCs）并不是治疗标准的关键方式，它可以作为目标。尽管在治疗的患者中成功抑制了HBV复制，但它们仍然有发展为HCC的风险。以乙肝表面抗原（HBsAg）丢失为特征的功能性治疗是新型抗病毒治疗的首要目标，而消除cccDNA的治疗仍是最终目标。总结总结出了新型治疗策略的发现和发展及其对cccDNA生物学的影响的最新进展。
最近的发现

在过去的十年中，对cccDNA生物学的理解取得了实质性进展，包括发现宿主重叠因子，cccDNA转录的表观遗传转化和免疫介导的降解。包括基因组编辑方法，针对宿主抑制因子或表观遗传基因转化的策略，核衣壳调节剂和免疫介导的降解。
摘要

尽管直接复制cccDNA策略仍处于临床前开发阶段，但衣壳装配调节剂和基于免疫的方法已进入临床阶段。逐步临床试验以评估其在患者中的功效和安全性，包括其对病毒cccDNA的影响。组合疗法提供了克服克服方法当前局限性的其他机会。

StephenW

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