Fourati Slim, Pawlotsky Jean-Michel
National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
F1000Res. 2016 Sep 6;5. doi: 10.12688/f1000research.8983.1. eCollection 2016.
Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs. Based on recent evidence showing trained immunity in immune-tolerant patients, the immune tolerance and immune clearance phases have been renamed the non-inflammatory and inflammatory phases, respectively. New diagnostic and monitoring tools are now available, including rapid diagnostic tests for hepatitis B surface antigen (HBsAg) detection, HBsAg quantification assays, anti-HBc antibody quantification assays, an HBV core-related antigen (HBcrAg) quantification test, new HBV DNA detection and quantification assays, and an HBV RNA quantification test. Their clinical utility is under study. Finally, new antiviral and immune modulation approaches are in the preclinical or early clinical developmental stages, with the goal to achieve functional cure or ideally (if possible) eradication of HBV infection.
全球约有2.4亿人感染乙型肝炎病毒(HBV)。本文综述了HBV感染在病毒学、免疫发病机制及诊断方面的最新进展。乙型肝炎病毒肝细胞特异性细胞受体——牛磺胆酸钠共转运多肽(NTCP)的鉴定,使得开发可靠的细胞培养系统以及更好地理解病毒生命周期的早期步骤成为可能。参与共价闭合环状DNA合成、稳定性及转录调控的病毒和宿主因子也已得到鉴定,并为新药提供了潜在靶点。基于近期在免疫耐受患者中发现的训练免疫的证据,免疫耐受期和免疫清除期分别被重新命名为非炎症期和炎症期。目前已有新的诊断和监测工具,包括用于检测乙型肝炎表面抗原(HBsAg)的快速诊断试验、HBsAg定量检测、抗-HBc抗体定量检测、HBV核心相关抗原(HBcrAg)定量检测、新的HBV DNA检测和定量检测以及HBV RNA定量检测。它们的临床实用性正在研究中。最后,新的抗病毒和免疫调节方法正处于临床前或早期临床开发阶段,目标是实现功能性治愈,理想情况下(如果可能)根除HBV感染。