Modeling hepatocyte apoptosis in chronic HCV infection with impulsive drug control.

Chronic hepatitis C virus (HCV) infection is one of the leading life-threatening diseases owing to its non-cytopathic nature and scarcity of vaccines to combat. Hepatocyte apoptosis casts extensive impact in regulating chronic HCV infection. We propose a four dimensional deterministic model scheming the role of hepatocyte apoptosis and significance of HCV-specific CTL response in the intermediate stages of chronic HCV infection. Numerical simulation indicates that unregulated behavior of hepatocyte apoptosis triggers hepatocellular carcinoma and prolonged continuation of apoptosis induces liver damages. The system undergoes backward bifurcation and the value of the basic reproduction number R 0 = 0.98 < 1 shows recurrence of infection. Local sensitivity analysis has been performed to reveal the most sensitive parameters responsible for the progression and mitigation of infection. In order to control of chronic HCV infection through pan-genotypic direct acting antiviral drugs (DAAs), impulsive differential equations are considered to study the effect of perfect drug adherence to both fixed and non-fixed dosing. For possible eradication of the chronic HCV infection, impulsive drug control suggests significant viral load reduction. The analytical results obtained for both non-impulsive and impulsive models are quantified biologically. • Role of hepatocyte apoptosis in intermediate stages of chronic HCV infection. • Apoptosis mediated by Perforin/GrB pathway is more effective than by CD95L ligand. • Occurrence of backward bifurcation indicates reinfection. • Impulsive differential equations are applied to study perfect adherence to DAAs. • Impulsive drug control suggests significant viral load reduction. [ABSTRACT FROM AUTHOR]