Kumar Rajneesh, Pérez-Del-Pulgar Sofía, Testoni Barbara, Lebossé Fanny, Zoulim Fabien
Cancer Research Center of Lyon (CRCL), INSERM U1052, CNRS 5286, Lyon, France.
Lyon University, F-69100, Villeurbanne, France.
Liver Int. 2016 Jan;36 Suppl 1:72-7. doi: 10.1111/liv.13001.
Hepatitis B virus (HBV) remains a public health concern with 240 million people affected worldwide. HBV is an hepadnavirus that replicates its genome in hepatocytes. One of the key steps of the viral life cycle is the formation of cccDNA - covalently closed circular DNA - in the nucleus, the equivalent of a viral mini-chromosome that acts as a template for subsequent virus replication. Current antiviral medications are not effective in eradicating cccDNA, which can persist in the infected liver even in the absence of detectable HBV DNA or HBsAg in the blood. cccDNA cannot be measured in serum, and few surrogate markers have been proposed. Persistent cccDNA has been associated with various clinical events, including viral reactivation induced by immunosuppressive therapies, HBV recurrence after liver transplantation and hepatocellular carcinoma (HCC). cccDNA remains the main target to achieve a cure of HBV infection, thus extensive efforts are being made to develop new antiviral concepts to degrade or silence cccDNA.
乙肝病毒（HBV）仍是一个公共卫生问题，全球有2.4亿人受到影响。HBV是一种嗜肝DNA病毒，其基因组在肝细胞中复制。病毒生命周期的关键步骤之一是在细胞核中形成cccDNA——共价闭合环状DNA，它相当于一个病毒微型染色体，可作为后续病毒复制的模板。目前的抗病毒药物无法有效根除cccDNA，即使血液中检测不到HBV DNA或HBsAg，cccDNA仍可在受感染的肝脏中持续存在。血清中无法检测到cccDNA，并且几乎没有提出替代标志物。持续存在的cccDNA与各种临床事件有关，包括免疫抑制疗法诱导的病毒再激活、肝移植后HBV复发以及肝细胞癌（HCC）。cccDNA仍然是实现治愈HBV感染的主要靶点，因此正在做出广泛努力来开发新的抗病毒概念以降解或沉默cccDNA。
