School of Biotechnology, Gautam Buddha University, Greater Noida, India.
Institute of Liver and Biliary Sciences, Delhi, India.
Exp Cell Res. 2023 Jul 1;428(1):113618. doi: 10.1016/j.yexcr.2023.113618. Epub 2023 May 2.
Hepatitis B Virus (HBV) is the prevailing cause of chronic liver disease, which progresses to Hepatocellular carcinoma (HCC) in 75% of cases. It represents a serious health concern being the fourth leading cause of cancer-related mortality worldwide. Treatments available to date fail to provide a complete cure with high chances of recurrence and related side effects. The lack of reliable, reproducible, and scalable in vitro modeling systems that could recapitulate the viral life cycle and represent virus-host interactions has hindered the development of effective treatments so far. The present review provides insights into the current in-vivo and in-vitro models used for studying HBV and their major limitations. We highlight the use of three-dimensional liver organoids as a novel and suitable platform for modeling HBV infection and HBV-mediated HCC. HBV organoids can be expanded, genetically altered, patient-derived, tested for drug discovery, and biobanked. This review also provides the general guidelines for culturing HBV organoids and highlights their several prospects for HBV drug discovery and screening.
乙型肝炎病毒（HBV）是慢性肝病的主要病因，其中 75%的病例会进展为肝细胞癌（HCC）。HBV 是全球癌症相关死亡的第四大主要原因，这是一个严重的健康问题。目前可用的治疗方法无法提供完全治愈的效果，复发的几率很高，且存在相关副作用。缺乏可靠、可重复和可扩展的体外建模系统来重现病毒的生命周期和代表病毒-宿主相互作用，这在很大程度上阻碍了有效的治疗方法的发展。本文综述了目前用于研究 HBV 的体内和体外模型及其主要局限性。我们强调了使用三维肝类器官作为一种新颖且合适的平台来模拟 HBV 感染和 HBV 介导的 HCC。HBV 类器官可以进行扩增、基因修饰、患者来源、用于药物发现测试和生物库存储。本文还提供了培养 HBV 类器官的一般指南，并强调了它们在 HBV 药物发现和筛选方面的几个前景。
