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Abstract：
Hepatitis B liver infection is caused by hepatitis B virus (HBV) and represents a major global disease problem when it becomes chronic, as is the case for 80-90% of vertical or early life infections. However, in the vast majority (>95%) of adult exposures, the infected individuals are capable of mounting an effective immune response leading to infection resolution. A good understanding of HBV dynamics and the interaction between the virus and immune system during acute infection represents an essential step to characterize and understand the key biological processes involved in disease resolution, which may help to identify potential interventions to prevent chronic hepatitis B. In this work, a quantitative systems pharmacology model for acute hepatitis B characterizing viral dynamics and the main components of the innate, adaptive, and tolerant immune response has been successfully developed. To do so, information from multiple sources and across different organization levels has been integrated in a common mechanistic framework. The final model adequately describes the chronology and plausibility of an HBV-triggered immune response, as well as clinical data from acute patients reported in the literature. Given the holistic nature of the framework, the model can be used to illustrate the relevance of the different immune pathways and biological processes to ultimate response, observing the negligible contribution of the innate response and the key contribution of the cellular response on viral clearance. More specifically, moderate reductions of the proliferation of activated cytotoxic CD8+ lymphocytes or increased immunoregulatory effects can drive the system towards chronicity.
摘要：
乙型肝炎肝脏感染是由乙型肝炎病毒（HBV）引起的，当它变成慢性时，它代表了一个主要的全球疾病问题，与80-90％的垂直或早期生命感染一样。然而,在绝大多数(>95%)的成人暴露中，受感染的个体能够产生有效的免疫反应，从而解决感染。在急性感染期间，对HBV动力学以及病毒与免疫系统之间的相互作用的良好理解代表了表征和了解疾病解决中涉及的关键生物过程的重要步骤，这可能有助于确定预防慢性乙型肝炎的潜在干预措施。急性乙型肝炎的定量系统药理学模型表征病毒动力学和先天的主要成分，适应性，并成功开发了耐受性免疫应答。要做到这一点，来自多个来源和不同组织级别的信息已集成在一个共同的机制框架中。最终模型充分描述了HBV触发的免疫反应的时间顺序和合理性，以及文献报道的急性患者的临床数据。鉴于该框架的整体性，该模型可用于说明不同免疫途径和生物过程与最终反应的相关性，观察先天反应的微不足道的贡献和细胞反应对病毒清除的关键贡献。更具体地说,激活的细胞毒性CD8+淋巴细胞增殖的适度减少或免疫调节作用的增加可以驱动系统走向慢性。
