Modeling hepatitis C virus dynamics: liver regeneration and critical drug efficacy

J Theor Biol. 2007 Jul 21;247(2):371-81. doi: 10.1016/j.jtbi.2007.03.006. Epub 2007 Mar 14.

Abstract

Mathematical models for hepatitis C viral (HCV) RNA kinetics have provided a means of evaluating the antiviral effectiveness of therapy, of estimating parameters such as the rate of HCV RNA clearance, and they have suggested mechanism of action against HCV for both interferon and ribavirin. Nevertheless, the model that was originally formulated by Neumann et al. [1998. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 282 (5386), 103-107] is unable to explain all of the observed HCV RNA profiles under treatment e.g., a triphasic viral decay and a viral rebound to baseline values after the cessation of therapy. Further, the half-life of productively HCV-infected cells, estimated from the second phase HCV RNA decline slope, is very variable and sometimes zero with no clear understanding of why. We show that extending the original model by including hepatocyte proliferation yields a more realistic model without any of these deficiencies. Further, we define and characterize a critical drug efficacy, such that for efficacies above the critical value HCV is ultimately cleared, while for efficacies below it, a new chronically infected viral steady-state level is reached.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Hepacivirus / drug effects
  • Hepacivirus / physiology*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / virology*
  • Humans
  • Liver Regeneration*
  • Models, Biological*
  • Treatment Outcome

Substances

  • Antiviral Agents