Institute of Medical Virology, Justus Liebig University of Giessen, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Schubertstr. 81, 35392, Giessen, Germany; German Center for Infection Research (DZIF), Partner Sites Giessen, Heidelberg, Hannover, Germany.
Institute of Medical Virology, Justus Liebig University of Giessen, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Schubertstr. 81, 35392, Giessen, Germany.
Antiviral Res. 2021 Feb;186:104973. doi: 10.1016/j.antiviral.2020.104973. Epub 2020 Nov 6.
Hepatitis B virus (HBV) poses a major global health burden with 260 million people being chronically infected and 890,000 dying annually from complications in the course of the infection. HBV is a small enveloped virus with a reverse-transcribed DNA genome that infects hepatocytes and can cause acute and chronic infections of the liver. HBV is endemic in humans and apes representing the prototype member of the viral family Hepadnaviridae and can be divided into 10 genotypes. Hepadnaviruses have been found in all vertebrate classes and constitute an ancient viral family that descended from non-enveloped progenitors more than 360 million years ago. The de novo emergence of the envelope protein gene was accompanied with the liver-tropism and resulted in a tight virus-host association. The oldest HBV genomes so far have been isolated from human remains of the Bronze Age and the Neolithic (~7000 years before present). Despite the remarkable stability of the hepadnaviral genome over geological eras, HBV is able to rapidly evolve within an infected individual under pressure of the immune response or during antiviral treatment. Treatment with currently available antivirals blocking intracellular replication of HBV allows controlling of high viremia and improving liver health during long-term therapy of patients with chronic hepatitis B (CHB), but they are not sufficient to cure the disease. New therapy options that cover all HBV genotypes and emerging viral variants will have to be developed soon. In addition to the antiviral treatment of chronically infected patients, continued efforts to expand the global coverage of the currently available HBV vaccine will be one of the key factors for controlling the rising global spread of HBV. Certain improvements of the vaccine (e.g. inclusion of PreS domains) could counteract known problems such as low or no responsiveness of certain risk groups and waning anti-HBs titers leading to occult infections, especially with HBV genotypes E or F. But even with an optimal vaccine and a cure for hepatitis B, global eradication of HBV would be difficult to achieve because of an existing viral reservoir in primates and bats carrying closely related hepadnaviruses with zoonotic potential.
乙型肝炎病毒（HBV）是一个全球性的主要健康负担，全球有 2.6 亿人慢性感染，每年有 89 万人死于感染过程中的并发症。HBV 是一种带有逆转录 DNA 基因组的小包膜病毒，感染肝细胞，可引起急性和慢性肝脏感染。HBV 在人类和猿类中流行，代表了病毒家族嗜肝 DNA 病毒科的原型成员，可分为 10 个基因型。在所有脊椎动物中都发现了嗜肝 DNA 病毒，它们构成了一个古老的病毒家族，起源于 3.6 亿多年前的非包膜前体。包膜蛋白基因的从头出现伴随着肝嗜性，并导致了紧密的病毒-宿主关联。迄今为止，最古老的 HBV 基因组是从青铜时代和新石器时代（距今约 7000 年前）的人类遗骸中分离出来的。尽管 HBV 的基因组在地质时代非常稳定，但在感染个体中，在免疫反应或抗病毒治疗的压力下，HBV 能够迅速进化。目前可用的抗病毒药物可阻断 HBV 的细胞内复制，从而控制高病毒血症并改善慢性乙型肝炎（CHB）患者的肝脏健康，但不足以治愈该疾病。新的治疗方案需要尽快涵盖所有 HBV 基因型和新兴病毒变异体。除了对慢性感染患者的抗病毒治疗外，继续努力扩大目前可用 HBV 疫苗的全球覆盖率将是控制 HBV 在全球传播的关键因素之一。疫苗的某些改进（例如包含 PreS 结构域）可以克服某些已知问题，例如某些风险群体的反应率低或无反应性以及抗-HBs 滴度下降导致隐匿性感染，特别是与 HBV 基因型 E 或 F 相关的感染。但即使有了最佳的疫苗和乙型肝炎的治疗方法，由于携带具有人畜共患潜力的密切相关嗜肝 DNA 病毒的灵长类动物和蝙蝠中存在现有的病毒库，全球根除 HBV 也将难以实现。
