Li Juan, Liu Siyi, Zang Qijuan, Yang Ruijie, Zhao Yingren, He Yingli
Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Chin Med J (Engl). 2024 Dec 5;137(23):2821-2832. doi: 10.1097/CM9.0000000000003178. Epub 2024 Jun 28.
Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
慢性乙型肝炎病毒（HBV）感染是一个全球公共卫生问题。现有的抗病毒药物，包括核苷（酸）类似物和α干扰素，可抑制HBV复制并改善预后。然而，共价闭合环状DNA（cccDNA）的持续存在、HBV-DNA整合到宿主基因组以及免疫反应受损阻碍了乙型肝炎的成功治疗。虽然目前的治疗方法仍难以实现HBV的功能性治愈，但这是新治疗方法的目标。因此，开发新型抗病毒药物对于实现慢性乙型肝炎的功能性或完全治愈是必要的。近年来，在HBV感染的药物发现和开发方面取得了重大进展。直接作用抗病毒药物，如进入抑制剂、衣壳组装调节剂、亚病毒颗粒释放抑制剂、cccDNA沉默剂和RNA干扰分子已进入临床试验。此外，几种免疫调节剂，包括Toll样受体激动剂、治疗性疫苗、检查点抑制剂和单克隆抗体，也正走向临床应用。在本综述中，我们总结了慢性乙型肝炎治疗的最新进展和局限性，并讨论了实现功能性治愈方法的前景。尽管这些新的抗病毒药物在临床实践中广泛应用还需要一些时间，但联合治疗可能会成为未来更可取的治疗选择。
