Sensitivity analysis of chronic hepatitis C virus infection with immune response and cell proliferation

Abstract

A new mathematical model of chronic hepatitis C virus (HCV) infection incorporating humoral and cell-mediated immune responses, distinct cell proliferation rates for both uninfected and infected hepatocytes, and antiviral treatment all at once, is formulated and analyzed meticulously. Analysis of the model elucidates the existence of multiple equilibrium states. Moreover, the model has a locally asymptotically stable disease-free equilibrium (DFE) whenever the basic reproduction number is less than unity. Local sensitivity analysis (LSA) result exhibits that the most influential (negatively sensitive) parameters on the epidemic threshold are the drug efficacy of blocking virus production and the drug efficacy of removing infection. However, LSA does not accurately assess uncertainty and sensitivity in the system and may mislead us since by default this technique holds all other parameters fixed at baseline values. To overcome this pitfall, one of the most robust and efficient global sensitivity analysis (GSA) methods, which is Latin hypercube sampling-partial rank correlation coefficient technique, elucidates that the proliferation rate of infected hepatocytes and the drug efficacy of killing infected hepatocytes are highly sensitive parameters that affect the transmission dynamics of HCV in any population. Our study suggests that cell proliferation of the infected hepatocytes can be very crucial in controlling disease outbreak. Thus, a future HCV drug that boosts cell-mediated immune response is expected to be quite effective in controlling disease outbreak.