Leowattana Wattana, Leowattana Tawithep
Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
World J Virol. 2022 Jan 25;11(1):57-72. doi: 10.5501/wjv.v11.i1.57.
Chronic hepatitis B (CHB) infection remains the most causative agent of liver-related morbidity and mortality worldwide. It impacts nearly 300 million people. The current treatment for chronic infection with the hepatitis B virus (HBV) is complex and lacks a durable treatment response, especially hepatitis B surface antigen (HBsAg) loss, necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA (cccDNA). New drugs that target distinct steps of the HBV life cycle have been investigated, which comprise inhibiting the entry of HBV into hepatocytes, disrupting or silencing HBV cccDNA, modulating nucleocapsid assembly, interfering HBV transcription, and inhibiting HBsAg release. The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication. This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs. Hopefully, with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle, the ultimate eradication of CHB infection will soon be achieved.
慢性乙型肝炎(CHB)感染仍然是全球肝脏相关发病和死亡的最主要病因。它影响着近3亿人。目前针对乙型肝炎病毒(HBV)慢性感染的治疗复杂,且缺乏持久的治疗反应,尤其是乙肝表面抗原(HBsAg)消失,由于HBV共价闭合环状DNA(cccDNA)持续存在,大多数CHB患者需要接受长期治疗。针对HBV生命周期不同步骤的新型药物已在研究中,包括抑制HBV进入肝细胞、破坏或沉默HBV cccDNA、调节核衣壳组装、干扰HBV转录以及抑制HBsAg释放。实现CHB患者的功能性治愈或持续HBsAg消失是朝着根除HBV的下一步措施。本综述将探讨新型直接作用抗HBV药物研发的最新进展。有望通过将目前的抗病毒药物与新研发的针对HBV生命周期不同步骤的直接作用抗病毒药物联合使用,不久就能实现CHB感染的最终根除。