Noordeen Faseeha
Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
Virusdisease. 2015 Jun;26(1-2):1-8. doi: 10.1007/s13337-015-0247-y. Epub 2015 Apr 5.
Hepatitis B virus (HBV) currently infects an estimated population of 2 billion individuals in the world, including 400 million people with chronic HBV infection. HBV virology, replication and the host's immune response to HBV infection contribute to different infection outcomes. Acute hepatitis HBV infection is self-limiting but it leaves a residual infection that can become active in an individual during immunosuppression. In chronic HBV infection, the virus persistently replicates in hepatocytes leading to immune mediated hepatocellular damage. Despite the inability to remove the virus in more than 70 % of patients, current treatments for chronic HBV infection, interferon alpha and antiviral nucleotide/nucleoside analogues, aim to reduce viral replication to prevent or at least delay the progression to cirrhosis and hepatocellular carcinoma. In both self resolved acute and persistent HBV infection, the long term existence of chromatinised covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes cannot be targeted by current treatments to eliminate these templates to eradicate the viral persistence. Identifying the mechanisms involve in the removal of infected hepatocytes will be useful as treatment options. In this context, DNA based novel therapeutic and immunization strategies might help to remove stable cccDNA and thus viral persistence.
目前，全球估计有20亿人感染乙型肝炎病毒（HBV），其中4亿人患有慢性HBV感染。HBV病毒学、复制以及宿主对HBV感染的免疫反应导致了不同的感染结果。急性HBV感染具有自限性，但会留下残余感染，在免疫抑制期间，个体体内的残余感染可能会激活。在慢性HBV感染中，病毒在肝细胞中持续复制，导致免疫介导的肝细胞损伤。尽管超过70%的患者无法清除病毒，但目前用于治疗慢性HBV感染的药物，如α干扰素和抗病毒核苷酸/核苷类似物，旨在减少病毒复制，以预防或至少延缓肝硬化和肝细胞癌的进展。在自限性急性和持续性HBV感染中，目前的治疗方法都无法靶向感染肝细胞细胞核中染色质化的共价闭合环状DNA（cccDNA）的长期存在，从而消除这些模板以根除病毒持续性感染。确定参与清除感染肝细胞的机制将有助于提供治疗选择。在这种情况下，基于DNA的新型治疗和免疫策略可能有助于清除稳定的cccDNA，从而消除病毒持续性感染。
