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

被引:140
作者
Dahari, Harel
Lo, Arthur
Ribeiro, Ruy M.
Perelson, Alan S.
机构
[1] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[2] Entelos Corp, Foster City, CA 94404 USA
关键词
mathematical modeling; hepatitis C virus; viral kinetics; critical drug efficacy; liver regeneration;
D O I
10.1016/j.jtbi.2007.03.006
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Published by Elsevier Ltd.
引用
收藏
页码:371 / 381
页数:11
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