Global Dynamics and Implications of an HBV Model with Proliferating Infected Hepatocytes
Global Dynamics and Implications of an HBV Model with Proliferating Infected Hepatocytes
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DOI：
10.3390/app11178176
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
S. Hews;S. Eikenberry;J. Nagy;Tin Phan;Yang Kuang
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文献类型：
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作者：
S. Hews;S. Eikenberry;J. Nagy;Tin Phan;Yang Kuang
慢性乙型肝炎(乙肝)感染是人类痛苦的一个主要原因，许多数学模型已经研究了这种疾病的宿主内动态。以前的大多数模型都假设感染的肝细胞不会增殖；然而，乙肝病毒感染对肝细胞增殖的影响是有争议的，显示出诱导和抑制增殖的数据相互矛盾。利用一族常微分方程组(ODE)模型，我们研究了乙肝病毒感染的肝细胞增殖的动态影响。在这里，我们表明，在这类模型中感染的肝细胞增殖产生一个阈值，该阈值将动力学分为两类。受感染细胞的增殖受到充分抑制会产生以病毒载量振荡为特征的复杂动力学，而较高的增殖会产生直接的动力学，总是会导致慢性感染，有时还会导致肝功能衰竭。肝功能衰竭状态的全局稳定性结果被包括在内，因为它是这类模型所独有的。最后，模型分析激发了一个可检验的生物学假说：当且仅当感染的肝细胞的增殖受到严重损害时，健康的肝细胞才存在于慢性乙肝感染中。
Chronic hepatitis B (HBV) infection is a major cause of human suffering, and a number of mathematical models have examined the within-host dynamics of the disease. Most previous models assumed that infected hepatocytes do not proliferate; however, the effect of HBV infection on hepatocyte proliferation is controversial, with conflicting data showing both induction and inhibition of proliferation. With a family of ordinary differential equation (ODE) models, we explored the dynamical impact of proliferation among HBV-infected hepatocytes. Here, we show that infected hepatocyte proliferation in this class of models generates a threshold that divides the dynamics into two categories. Sufficiently compromised proliferation in infected cells produces complex dynamics characterized by oscillating viral loads, whereas higher proliferation generates straightforward dynamics that always results in chronic infection, sometimes with liver failure. A global stability result of the liver failure state was included as it is unique to this class of models. Finally, the model analysis motivated a testable biological hypothesis: Healthy hepatocytes are present in chronic HBV infection if and only if the proliferation of infected hepatocytes is severely impaired.