Modeling hepatitis C virus (HCV) dynamics: Relating intracellular (in vitro) and extracellular (in vivo) HCV kinetics under treatment

Modeling hepatitis C virus (HCV) dynamics: Relating intracellular (in vitro) and extracellular (in vivo) HCV kinetics under treatment.

Harel Dahari Department of Medicine, Section of Hepatology, University of Illinois at Chicago, Chicago, IL, USA.

Mathematical models of the dynamics of hepatitis C virus (HCV) have proven to be of great utility in understanding viral infection, pathogenesis and designing better treatments. Recently, we included hepatocyte proliferation in the original model of HCV infection and introduced a new notion of critical drug efficacy. These new features allow us to predict complex HCV RNA kinetics seen in serum of treated patients, and suggest why patients with high baseline viral load or with advanced liver disease are difficult to treat. Importantly, however, these models were designed to predict extracellular (i.e., in serum) viral kinetics as part of the kinetics of both uninfected and infected cells which cannot be measured with the current techniques in treated patients. Theoretically, if HCV extracellular HCV RNA kinetics mainly reflects intracellular HCV RNA kinetics then our current understanding of HCV dynamics under treatment should be updated. Therefore, relating intracellular and extracellular HCV RNA kinetics is of great importance. Current modeling efforts and new data from treated mice and cell culture will be presented.