Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

作     者：Maurizia Rossana Brunetto Piero Colombatto Ferruccio Bonino 

作者机构：UO Epatologia Azienda Ospedaliero-Universitaria Pisana 56100 Pisa Italy Direzione Scientifica Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli and Regina Elena di Milano 20122 Milano Italy 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2009年第15卷第5期

页      面：531-537页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：Viral hepatitis Bio-mathematical models Hepatitis B virus Hepatitis C virus Viral dynamics 

摘      要：The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the f irst 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an automatic pilot for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.