摘要
慢性HBV感染是全球性的公共卫生问题,同时也是导致肝硬化和肝癌等终末期肝病的主要病因,严重威胁人类健康。近年来,随着“临床治愈”概念的提出,目前认为临床治愈是慢性乙型肝炎(chronic hepatitis B, CHB)理想的治疗终点,但实现临床治愈面临着巨大的挑战。尽管现有2类抗病毒药物,即核苷(酸)类似物和聚乙二醇化干扰素(pegylated interferon, PEG-IFN)能够有效地抑制外周血HBV DNA复制,但由于HBV的复制源头共价闭合环状DNA(covalently closed circular DNA, cccDNA)在受感染的肝细胞内以微染色体的形式稳定存在,加之HBV感染过程中普遍发生HBV DNA整合以及免疫逃逸,导致CHB难以彻底治愈。HBV DNA抑制后序贯/联合PEG-IFN会增加HBsAg清除率。抑制病毒进入、翻译和HBsAg分泌,调节衣壳组装和靶向cccDNA转录/降解的新型抗病毒药物在临床试验中已显示出积极效果。包括免疫检查点抑制剂、治疗性疫苗、基因工程T细胞以及激活固有免疫应答在内的多种新型免疫调节疗法也在探索中。本文总结了现阶段CHB临床治愈的方法,并探讨了实现临床治愈可能的新策略,为未来全面实现临床治愈指明方向。
Chronic HBV infections remaina global public health problem, leading to end-stage liver diseases, such as liver cirrhosis and hepatocellular carcinomas, which seriously threaten human health. With the introduction of the “clinical cure”, it is considered as an ideal treatment endpoint for chronic hepatitis B(CHB). However, there are still great challenges to achieve a clinical cure. Although 2kinds of antiviral drugs, nucleos(t)ide analogues and pegylated interferon(PEG-IFN), can effectively inhibit the replication of HBV DNA in peripheral blood. The covalently closed circular(cccDNA), the source of HBV replication, is stably stored in the infected hepatocytes in the form of micro chromosomes. In addition, HBV DNA integration as well as immune escape, are common in HBV infection, making it difficult to be sterilizing cured. Switching to/adding on PEG-IFN after HBV DNA suppression increases the chance of HBsAg clearance. Novel antiviral reagents that inhibit viral entry, translation, and secretion of HBsAg, modulate capsid assembly, or target cccDNA transcription/degradation have shown promise in clinical trials. Various novel immunomodulatory approaches are also being explored, including immune checkpoint inhibitors, therapeutic vaccines, genetically engineered T cells, and stimulation of innate immune responses. In this review, we summarized the current approaches for curing CHB infection and discussed the possible novel strategies to achieve a clinical cure aimed to point out the way to achieve comprehensive clinical cure in the future.
作者
杨娜
康文
YANG Na;KANG Wen(Infectious Diseases,Xi’an Medical University,710068,China;Department of Infectious Diseases,The Second Affiliated Hospital of the Air Force Military Medical University,Xi’an 710038,China)
出处
《传染病信息》
2023年第1期73-79,共7页
Infectious Disease Information
基金
“十三五”国家科技重大专项(2017ZX10202101)。
