Shechter Oren, Sausen Daniel G, Dahari Harel, Vaillant Andrew, Cotler Scott J, Borenstein Ronen
Eastern Virginia Medical School, Norfolk, VA 23501, USA.
Naval Medical Center Portsmouth, Portsmouth, VA 23708, USA.
Int J Mol Sci. 2025 Apr 11;26(8):3633. doi: 10.3390/ijms26083633.
The Hepatitis B Virus (HBV) presents a formidable global health challenge, impacting hundreds of millions worldwide and imposing a considerable burden on healthcare systems. The elusive nature of the virus, with its ability to establish chronic infection and evade immune detection, and the absence of curative agents have prompted efforts to develop novel therapeutic approaches beyond current antiviral treatments. This review addresses the challenging concept of a functional cure for HBV, a state characterized by the suppression of HBV and HBsAg, mitigating disease progression and transmission without a complete cure. We provide an overview of HBV epidemiology and its clinical impact, followed by an exploration of the current treatment landscape and its limitations. The immunological basis of a functional cure is then discussed, exploring the intricate interplay between the virus and the host immune response. Emerging therapeutic approaches, such as RNA interference-based interventions, entry inhibitors, nucleic acid polymers, and therapeutic vaccines, are discussed with regard to their success in achieving a functional cure. Lastly, the review underscores the urgent need for innovative strategies to achieve a functional cure for HBV.
乙型肝炎病毒(HBV)给全球健康带来了严峻挑战,影响着全球数亿人,并给医疗系统带来了相当大的负担。该病毒难以捉摸,能够建立慢性感染并逃避免疫检测,而且缺乏治愈药物,这促使人们努力开发超越当前抗病毒治疗的新型治疗方法。本综述探讨了HBV功能性治愈这一具有挑战性的概念,该状态的特征是抑制HBV和乙肝表面抗原(HBsAg),减轻疾病进展和传播,但并非完全治愈。我们概述了HBV的流行病学及其临床影响,随后探讨了当前的治疗现状及其局限性。接着讨论了功能性治愈的免疫学基础,探究病毒与宿主免疫反应之间复杂的相互作用。还讨论了新兴的治疗方法,如基于RNA干扰的干预措施、进入抑制剂、核酸聚合物和治疗性疫苗,以及它们在实现功能性治愈方面的成效。最后,本综述强调了采取创新策略实现HBV功能性治愈的迫切需求。