Dahari Harel, Shudo Emi, Ribeiro Ruy M, Perelson Alan S
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Methods Mol Biol. 2009;510:439-53. doi: 10.1007/978-1-59745-394-3_33.
In the last decade, 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 and of estimating parameters, such as the rate of virion clearance and the rate of loss of HCV-infected cells, and they have suggested mechanisms of action for both interferon-alpha and ribavirin. The inclusion of homeostatic proliferation of infected and uninfected hepatocytes in existing viral kinetic models has allowed prediction of most observed HCV RNA profiles under treatment, for example, biphasic and triphasic viral decay and viral rebound to baseline values after the cessation of therapy. In addition, new kinetic models have taken into consideration the different pharmacokinetics of standard and pegylated forms of interferon and 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. Here, we describe our current understanding of the kinetics of HCV infection and treatment.
在过去十年中，病毒动力学模型在抗病毒治疗开始后丙型肝炎病毒（HCV）RNA衰减分析中发挥了重要作用。这些模型提供了一种评估治疗抗病毒效果以及估算诸如病毒粒子清除率和HCV感染细胞损失率等参数的方法，并且它们还揭示了α干扰素和利巴韦林的作用机制。在现有的病毒动力学模型中纳入受感染和未受感染肝细胞的稳态增殖，使得能够预测治疗过程中观察到的大多数HCV RNA谱，例如双相和三相病毒衰减以及治疗停止后病毒反弹至基线值。此外，新的动力学模型考虑了标准干扰素和聚乙二醇化干扰素不同的药代动力学，并纳入了丙氨酸转氨酶动力学和免疫反应方面的内容，以更全面地描绘治疗期间HCV RNA变化背后的生物学特性。在此，我们描述了我们目前对HCV感染和治疗动力学的理解。
