HBV cure: why, how, when?
HBV cure: why, how, when?
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DOI：
10.1016/j.coviro.2016.06.003
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发表时间：
2016-06-01
影响因子：
5.9
通讯作者：
Zoulim, Fabien
中科院分区：
文献类型：
--
作者：
Levrero, Massimo;Testoni, Barbara;Zoulim, Fabien
目前的HBV治疗控制了绝大多数治疗患者的复制和肝病进展。然而，HBV患者通常需要终身治疗，因为转录活性病毒cccDNA微型染色体在细胞核中持续存在，目前的抗病毒治疗并不直接靶向该染色体。HBV的真正完全治愈需要从所有感染的肝细胞中清除核内cccDNA。一个中间但仍然相关的步骤，将允许治疗停止将达到功能性治愈，相当于解决急性感染，持久的HBsAg损失抗-HBs血清转换，不可检测的血清DNA和持续的cccDNA在转录非活性状态。技术和药物科学的最新进展，包括主要HBV受体（即NTCP转运蛋白）的克隆和体外HBV感染模型的开发，预示着创新的抗病毒和免疫治疗方法的新视野。
Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status. Recent advances in technologies and pharmaceutical sciences, including the cloning of the mayor HBV receptor (i.e. the NTCP transporter) and the development in vitro HBV infection models, have heralded a new horizon of innovative antiviral and immune-therapeutic approaches.