Advances in Parameter Estimation for Mathematical Models of Hepatitis C Viral Kinetics

Mathematical models, some of which incorporate both intracellular and extracellular hepatitis C viral dynamics, have been advanced in recent years to study HCV-host kinetics and antivirals mode of action and efficacy. The standard hepatitis C virus (HCV) dynamic model keeps track of uninfected hepatocytes, infected hepatocytes, and free virus in blood. In multiscale models, a fourth equation accounts for the intracellular viral RNA (vRNA) kinetics in an infected cell. A multiscale model with vRNA kinetics consideration is substantially more difficult to solve, with the governing differential equations that are stiff. In previous contributions, we developed and implemented stable and efficient numerical methods for both the solution of the model equations and parameter estimation. In this contribution, we perform sensitivity analysis on model parameters to gain insight on important properties of these models and to ensure our numerical methods can be safely used for HCV viral dynamic simulations.