Dahari Harel, Guedj Jeremie, Perelson Alan S, Layden Thomas J
Department of Medicine, Section of Hepatology, The University of Illinois at Chicago 840 S. Wood Street MC787, Chicago, IL 60612.
Curr Hepat Rep. 2011 Jul 2;10(3):214-227. doi: 10.1007/s11901-011-0101-7.
In the last decade hepatitis C virus (HCV) kinetics has become an important clinical tool for the optimization of therapy with (pegylated)-interferon-α (IFN) and ribavirin (RBV). Mathematical models have generated important insights into HCV pathogenesis, HCV- host dynamics, and IFN and RBV's modes of action. Clinical trials with direct acting agents (DAAs) against various steps of the HCV life cycle have revealed new viral kinetic patterns that have not been observed with IFN±RBV. Very recently, studies have showed that single nucleotide polymorphisms (SNPs) in the IL28B gene region were associated with race/ethnicity and with response to IFN±RBV. Here we review our current knowledge of HCV kinetics and related mathematical models during IFN±RBV and/or DAA based therapies, HCV pathogenesis, and the role of IL28B polymorphism on early HCV kinetics. Better understanding of the mode of actions of drug(s) and viral kinetics may help to develop, in the near future, new individualized therapeutic regimens that include DAAs in combination with IFN+RBV.
在过去十年中，丙型肝炎病毒（HCV）动力学已成为优化聚乙二醇化干扰素-α（IFN）和利巴韦林（RBV）治疗方案的重要临床工具。数学模型为HCV发病机制、HCV与宿主的动态关系以及IFN和RBV的作用方式提供了重要见解。针对HCV生命周期各个步骤的直接作用抗病毒药物（DAA）的临床试验揭示了一些新的病毒动力学模式，这些模式在IFN±RBV治疗中未曾观察到。最近，研究表明IL28B基因区域的单核苷酸多态性（SNP）与种族和对IFN±RBV的反应有关。在此，我们综述了目前关于基于IFN±RBV和/或DAA治疗期间的HCV动力学及相关数学模型、HCV发病机制以及IL28B多态性对早期HCV动力学的作用的认识。更好地理解药物作用模式和病毒动力学可能有助于在不久的将来开发新的个体化治疗方案，包括将DAA与IFN+RBV联合使用。
