Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy
Modeling hepatitis C virus dynamics: Liver regeneration and critical drug efficacy
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DOI：
10.1016/j.jtbi.2007.03.006
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发表时间：
2007-07-21
影响因子：
2
通讯作者：
Perelson, Alan S.
中科院分区：
文献类型：
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作者：
Dahari, Harel;Lo, Arthur;Perelson, Alan S.
丙型肝炎病毒（HCV）RNA动力学的数学模型提供了一种手段来评估治疗的抗病毒效果，估计参数，如HCV RNA清除率，他们提出了干扰素和利巴韦林抗HCV的作用机制。然而，最初由Neumann等人[1998.丙型肝炎病毒在体内的动力学和干扰素α治疗的抗病毒疗效。Science 282（5386），103-107]不能解释在治疗下观察到的所有HCV RNA谱，例如，三阶段病毒衰减和治疗停止后病毒反弹至基线值。此外，根据第二阶段HCV RNA下降斜率估计的生产性HCV感染细胞的半衰期非常可变，有时为零，原因不明。我们表明，扩展原始模型，包括肝细胞增殖产生一个更现实的模型，没有任何这些缺陷。此外，我们定义并表征了关键药物功效，使得对于高于临界值的功效，HCV最终被清除，而对于低于临界值的功效，达到新的慢性感染病毒稳态水平。爱思唯尔有限公司出版
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.