Georgetown University Medical Center, Washington, DC 20057, USA.
Viruses. 2022 Aug 3;14(8):1711. doi: 10.3390/v14081711.
Infection with hepatitis B virus (HBV) is responsible for the increasing global hepatitis burden, with an estimated 296 million people being carriers and living with the risk of developing chronic liver disease and cancer. While the current treatment options for chronic hepatitis B (CHB), including oral nucleos(t)ide analogs and systemic interferon-alpha, are deemed suboptimal, the path to finding an ultimate cure for this viral disease is rather challenging. The lack of suitable laboratory animal models that support HBV infection and associated liver disease progression is one of the major hurdles in antiviral drug development. For more than four decades, experimental infection of the Eastern woodchuck with woodchuck hepatitis virus has been applied for studying the immunopathogenesis of HBV and developing new antiviral therapeutics against CHB. There are several advantages to this animal model that are beneficial for performing both basic and translational HBV research. Previous review articles have focused on the value of this animal model in regard to HBV replication, pathogenesis, and immune response. In this article, we review studies of drug development and preclinical evaluation of direct-acting antivirals, immunomodulators, therapeutic vaccines, and inhibitors of viral entry, gene expression, and antigen release in the woodchuck model of CHB since 2014 until today and discuss their significance for clinical trials in patients.
乙型肝炎病毒 (HBV) 感染是导致全球肝炎负担不断增加的原因，估计有 2.96 亿人携带 HBV，面临发展为慢性肝病和癌症的风险。虽然目前慢性乙型肝炎 (CHB) 的治疗选择，包括口服核苷（酸）类似物和全身干扰素-α，被认为并不理想，但找到这种病毒性疾病的最终治疗方法是相当具有挑战性的。缺乏支持 HBV 感染和相关肝病进展的合适的实验室动物模型是抗病毒药物开发的主要障碍之一。四十多年来，用土拨鼠肝炎病毒对东部土拨鼠进行实验性感染，一直被用于研究 HBV 的免疫发病机制，并开发针对 CHB 的新抗病毒疗法。这种动物模型有几个优点，有利于进行基础和转化的 HBV 研究。以前的综述文章主要关注该动物模型在 HBV 复制、发病机制和免疫反应方面的价值。在本文中，我们回顾了自 2014 年以来在 CHB 的土拨鼠模型中进行的直接作用抗病毒药物、免疫调节剂、治疗性疫苗以及病毒进入、基因表达和抗原释放抑制剂的药物开发和临床前评估研究，并讨论了它们对患者临床试验的意义。
