The Role of Proliferating Infected Hepatocytes on the Dynamics of an HBV-infected Liver
Chronic hepatitis B (HBV) infection is a major cause of human suffering, and a number of mathematical models have examined within-host dynamics of the disease. Previous models assume that infected hepatocytes do not proliferate; however, the effect of HBV infection on hepatocyte proliferation is con...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Text |
| Language: | English |
| Subjects: | |
| Online Access: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.188.4391 http://math.la.asu.edu/%7Ekuang/paper/Hews10.pdf |
| Summary: | Chronic hepatitis B (HBV) infection is a major cause of human suffering, and a number of mathematical models have examined within-host dynamics of the disease. Previous models assume 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 explore the dynamical impact of proliferation among HBV-infected hepatocytes. Here we show that proliferation of infected hepatocytes in this class of models generates a threshold that divides the dynamics into two categories. Sufficiently compromised proliferation of 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 is included as it is unique to this class of models. Finally, the model analysis motivates a testable biological hypothesis: healthy hepatocytes are present in chronic HBV infection if and only if the proliferation of infected hepatocytes is severely impaired. 1 |
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