Liu Qiuming, Yao Chenguang, Guo Xiaohong, Hu Kanghong
Bing Du Xue Bao. 2016 Sep;32(5):650-8.
The ultimate goal of chronic hepatitis B virus(HBV)therapy is full eradication of the virus from the liver. However, this is rarely achieved with the clinically available first-line agents (entecavir and tenofovir disoproxil fumarate) due to the inability to eliminate covalently closed circular DNA(cccDNA), which persists in the nucleus of infected hepatocyte cells,and failure of the host to induce an adequate specific immune response to control the infection. Currently, the clinical treatment for chronic HBV infection mainly includes nucleos(t)ide analogues (NAs), non-NAs and immune modulatory agents; however, each agent has individual advantages and drawbacks. It is, therefore, extremely urgent to identify novel targets involved in viral replication and develop novel anti-HBV drugs. In light of the breakthroughs in cccDNA research and host immune treatments, this review aims to summarize the state of the recent HBV drug research and development to highlight future therapeutic strategies to target the virus and host immune response.
慢性乙型肝炎病毒(HBV)治疗的最终目标是从肝脏中完全清除病毒。然而,由于无法消除共价闭合环状DNA(cccDNA),临床上可用的一线药物(恩替卡韦和替诺福韦酯)很少能实现这一目标。cccDNA存在于受感染肝细胞的细胞核中,并且宿主无法诱导足够的特异性免疫反应来控制感染。目前,慢性HBV感染的临床治疗主要包括核苷(酸)类似物(NAs)、非NAs和免疫调节剂;然而,每种药物都有其各自的优缺点。因此,确定参与病毒复制的新靶点并开发新型抗HBV药物迫在眉睫。鉴于cccDNA研究和宿主免疫治疗方面的突破,本综述旨在总结近期HBV药物研发的现状,以突出针对病毒和宿主免疫反应的未来治疗策略。