Afrin Nazia, Ciupe Stanca M, Conway Jessica M, Gulbudak Hayriye
Department of Mathematics, University of Louisiana at Lafayette, 104 E. University Circle Lafayette, Lafayette, 70503, LA, USA.
Department of Mathematics and Virginia Tech Center for the Mathematics of Biosystems, Virginia Tech, Blacksburg, VA, USA.
Math Biosci. 2025 May 31;387:109467. doi: 10.1016/j.mbs.2025.109467.
Understanding the mechanisms responsible for different clinical outcomes following hepatitis B infection requires a systems investigation of dynamical interactions between the virus and the immune system. To help elucidate mechanisms of protection and those responsible from transition from acute to chronic disease, we developed a deterministic mathematical model of hepatitis B infection that accounts for cytotoxic immune responses resulting in infected cell death, non-cytotoxic immune responses resulting in infected cell cure and protective immunity from reinfection, and cell proliferation. We analyzed the model and presented outcomes based on three important disease markers: the basic reproduction number R, the infected cells death rate δ (describing the effect of cytotoxic immune responses), and the liver carrying capacity K (describing the liver susceptibility to infection). Using asymptotic and bifurcation analysis techniques, we determined regions where virus is cleared, virus persists, and where clearance-persistence is determined by the size of viral inoculum. These results can guide the development of personalized intervention.
了解乙型肝炎感染后导致不同临床结果的机制需要对病毒与免疫系统之间的动态相互作用进行系统研究。为了帮助阐明保护机制以及从急性疾病转变为慢性疾病的机制，我们开发了一个乙型肝炎感染的确定性数学模型，该模型考虑了导致受感染细胞死亡的细胞毒性免疫反应、导致受感染细胞治愈的非细胞毒性免疫反应以及对再感染的保护性免疫，还有细胞增殖。我们分析了该模型，并基于三个重要的疾病标志物呈现结果：基本繁殖数R、受感染细胞死亡率δ（描述细胞毒性免疫反应的作用）和肝脏承载能力K（描述肝脏对感染的易感性）。使用渐近和分岔分析技术，我们确定了病毒被清除、病毒持续存在以及清除 - 持续存在由病毒接种量大小决定的区域。这些结果可以指导个性化干预措施的制定。
