Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur, India.
PLoS One. 2012;7(7):e41209. doi: 10.1371/journal.pone.0041209. Epub 2012 Jul 24.
Considerable progress has been made towards understanding hepatitis C virus, its pathogenesis and the effect of the drug therapy on the viral load, yet around 50% of patients do not achieve the sustained virological response (SVR) by the standard treatment. Although several personalized factors such as patients' age and weight may be important, by mathematical modeling we show that the time of the start of the therapy is a significant factor in determining the outcome. Toward this end, we first performed sensitivity analysis on the standard virus dynamics model. The analysis revealed four phases when the sensitivity of the infection to drug treatment differs. Further, we added a perturbation term in the model to simulate the drug treatment period and predict the outcome when the therapy is carried out during each of the four phases. The study shows that while the infection may be difficult to treat in the late phases, the therapy is likely to result in SVR if it is carried out in the first or second phase. Thus, development of newer and more sensitive screening methods is needed for the early detection of the infection. Moreover, the analysis predicts that the drug that blocks new infections is more effective than the drug that blocks the virus production.
在理解丙型肝炎病毒、其发病机制以及药物治疗对病毒载量的影响方面已经取得了相当大的进展,但仍有约 50%的患者无法通过标准治疗达到持续病毒学应答 (SVR)。尽管患者的年龄和体重等几个个性化因素可能很重要,但通过数学建模,我们表明治疗开始的时间是决定治疗结果的重要因素。为此,我们首先对标准病毒动力学模型进行了敏感性分析。分析表明,在感染对药物治疗的敏感性存在差异的四个阶段。此外,我们在模型中添加了一个摄动项来模拟药物治疗期,并预测在四个阶段中的每个阶段进行治疗时的结果。研究表明,虽然在后期感染可能难以治疗,但如果在第一或第二阶段进行治疗,治疗很可能会导致 SVR。因此,需要开发新的、更敏感的筛查方法来早期发现感染。此外,该分析预测,阻断新感染的药物比阻断病毒产生的药物更有效。