Global dynamics and implications of an HBV model with proliferating infected hepatocytes

Sarah Hews, Steffen Eikenberry, John D. Nagy, Tin Phan, Yang Kuang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number8176
JournalApplied Sciences (Switzerland)
Volume11
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • HBV
  • Hopf bifurcation
  • Logistic hepatocyte growth
  • Origin stability
  • Ratio-dependent transformation

ASJC Scopus subject areas

  • Materials Science(all)
  • Instrumentation
  • Engineering(all)
  • Process Chemistry and Technology
  • Computer Science Applications
  • Fluid Flow and Transfer Processes

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