Wang Gang, Guan Jun, Khan Nazif U, Li Guojun, Shao Junwei, Zhou Qihui, Xu Lichen, Huang Chunhong, Deng Jingwen, Zhu Haihong, Chen Zhi
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Institute for Hepatology, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, Shenzhen, 518112, Guangdong, China.
Gut Pathog. 2021 Apr 12;13(1):22. doi: 10.1186/s13099-021-00421-9.
Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients.
干扰素-α（IFN-α）和核苷（酸）类似物（NAs）是治疗慢性乙型肝炎病毒（HBV）感染的一线药物。一般来说，NAs作用于HBV前基因组RNA的逆转录，但它们无法消除共价闭合环状DNA（cccDNA）。尽管使用NAs进行有效治疗可显著降低HBV蛋白和DNA载量，甚至促进血清学转换，但由于缺乏有效的抗cccDNA药物，cccDNA仍存在于肝细胞的细胞核中。在目前可用的药物中，只有IFN-α可能作用于cccDNA。然而，在HBV患者的肝细胞中使用IFN-α根除cccDNA的临床效果并不理想，也未得到充分了解。在此，我们综述了IFN-α涉及cccDNA修饰的抗HBV机制，这是治愈HBV感染最有前景的方法。我们期望找到有前景的研究领域的迹象，这些领域需要进一步研究以消除患者体内的HBV cccDNA。
