Modeling complex decay profiles of hepatitis B virus during antiviral therapy.
Modeling complex decay profiles of hepatitis B virus during antiviral therapy.
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DOI：
10.1002/hep.22586
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发表时间：
2009-01
期刊：
影响因子：
13.5
通讯作者：
Perelson, Alan S.
中科院分区：
文献类型：
--
作者：
Dahari, Harel;Shudo, Emi;Ribeiro, Ruy M.;Perelson, Alan S.
典型地，在接受治疗的患者中，B型肝炎病毒（HBV）以双相方式衰减。然而，在一些治疗患者中也观察到了HBV DNA更复杂的衰变谱（例如，平坦部分应答、三相、逐步），但对其起源没有明确的了解。我们最近引入了临界药物功效εc的概念，使得如果总体药物功效εtot高于临界药物功效，即，如果εtot > εc，则病毒水平将在治疗中持续下降，而如果εtot < εc，则病毒载量将最初下降，但最终稳定在新的设定点，如在平坦部分应答者中所见。使用关键疗效的概念，并在病毒动力学模型中包括肝细胞增殖，我们可以解释这些复杂的HBV DNA衰变。该模型预测，复杂的配置文件，如那些表现出平台期或肩阶段，以及一类逐步下降，只发生在患者中的大部分肝细胞感染治疗前。总之，我们通过动力学模型显示了各种HBV DNA衰变谱如何在治疗患者中出现。
Typically, hepatitis B virus (HBV) decays in patients under therapy in a biphasic manner. However, more complex decay profiles of HBV DNA (e.g. flat partial response, triphasic, stepwise) have also been observed in some treated patients with no clear understanding of their origin. We recently introduced the notion of a critical drug efficacy, εc, such that if overall drug efficacy, εtot, is higher than the critical drug efficacy, i.e., εtot > εc, then viral levels will continually decline on therapy, while if εtot < εc then viral loads will initially decline but ultimately stabilize at a new set point, as seen in flat partial responders. Using the idea of critical efficacy and including hepatocyte proliferation in a viral kinetic model we can account for these complex HBV DNA decays. The model predicts that complex profiles such as those exhibiting a plateau or shoulder phase as well as a class of stepwise declines occur only in patients in whom the majority of hepatocytes are infected before therapy. In conclusion, we show via kinetic modeling how a variety of HBV DNA decay profiles can arise in treated patients.
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DOI：
10.1073/pnas.93.9.4398
发表时间：
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影响因子：
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作者：
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