New Kinetic Models for the Hepatitis C Virus *

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Abstract
Viral kinetic modeling has played an important role in the analysis of HCV RNA decay after the initiation of antiviral therapy. Models have provided a means of evaluating the antiviral effectiveness of therapy, of estimating parameters such as the rate of virion clearance and the rate of clearance of hepatitis C virus (HCV)–infected cells, and they have suggested mechanisms of action for both interferon and ribavirin. Nevertheless, the models that were originally formulated were unable to explain all of the observed HCV RNA profiles. We provide an update on the state of HCV kinetic modeling and discuss new models that have taken into consideration the different pharmacokinetics of standard and pegylated forms of interferon, allow for changes in drug effectiveness as drug concentrations fall between dosing intervals, and that have incorporated alanine aminotransferase kinetics and aspects of immune responses to provide a more comprehensive picture of the biology underlying changes in HCV RNA during therapy. (Hepatology 2005;42:749–754.)