Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):618-634. doi: 10.1038/s41575-020-0296-6. Epub 2020 May 28.
The global burden of hepatitis B virus (HBV) is enormous, with 257 million persons chronically infected, resulting in more than 880,000 deaths per year worldwide. HBV exists as nine different genotypes, which differ in disease progression, natural history and response to therapy. HBV is an ancient virus, with the latest reports greatly expanding the host range of the Hepadnaviridae (to include fish and reptiles) and casting new light on the origins and evolution of this viral family. Although there is an effective preventive vaccine, there is no cure for chronic hepatitis B, largely owing to the persistence of a viral minichromosome that is not targeted by current therapies. HBV persistence is also facilitated through aberrant host immune responses, possibly due to the diverse intra-host viral populations that can respond to host-mounted and therapeutic selection pressures. This Review summarizes current knowledge on the influence of HBV diversity on disease progression and treatment response and the potential effect on new HBV therapies in the pipeline. The mechanisms by which HBV diversity can occur both within the individual host and at a population level are also discussed.
全球乙型肝炎病毒（HBV）负担巨大，全球有 2.57 亿人慢性感染 HBV，每年导致超过 88 万人死亡。HBV 存在 9 种不同基因型，这些基因型在疾病进展、自然史和对治疗的反应方面存在差异。HBV 是一种古老的病毒，最近的报告大大扩展了嗜肝 DNA 病毒科（包括鱼类和爬行动物）的宿主范围，并为这种病毒家族的起源和进化提供了新的线索。尽管有有效的预防性疫苗，但慢性乙型肝炎仍无法治愈，这主要是由于当前疗法无法靶向的病毒微染色体持续存在。HBV 的持续存在也通过异常的宿主免疫反应得到促进，这可能是由于宿主内多样化的病毒种群能够对宿主和治疗选择压力做出反应。这篇综述总结了目前关于 HBV 多样性对疾病进展和治疗反应的影响的知识，以及对新的 HBV 治疗方法在研发中的潜在影响。还讨论了 HBV 多样性在个体宿主内和群体水平上发生的机制。
