标题： 乙型肝炎病毒感感染的年龄结构模型突显了不同治疗策略的潜力 显示英文标题

标题： An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies

摘要： 乙型肝炎病毒是一种全球健康威胁，世界卫生组织已将2030年前消除该病毒作为优先事项。 在这里，我们提出一个针对HBV感染的免疫反应的年龄结构模型，该模型考虑了细胞介导免疫和体液免疫的贡献。 该模型使用急性感染期间记录的已发表患者数据进行了验证。 通过改变免疫反应参数，该模型已被适应于慢性感染、感染清除和复发的情景。 分析了免疫反应耗竭和非感染性亚病毒颗粒对免疫反应动力学的影响。 在该模型背景下对不同治疗方案的比较表明，针对病毒生命周期方面的药物比耗竭疗法更有效，耗竭疗法是一种减轻免疫反应耗竭的治疗方法。 我们的结果表明，抗病毒治疗最好在病毒载量下降时开始，而不是在复发期。 该模型表明，快速的抗体生产速率总是导致病毒清除，突显了目前正在进行临床试验的抗体疗法的前景。 显示英文摘要

摘要： Hepatitis B virus is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always lead to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.