慢性乙型肝炎恩替卡韦治疗过程中病毒动力学特点分析

目的 分析抗病毒治疗过程中病毒载量动态变化特点及其临床意义.方法 采用Neumann数学模型对门诊口服恩替卡韦治疗并早期规则随访(0、2、4、12、24周)的6例慢性乙型肝炎患者的血HBV载量及其相关参数进行分析.结果 恩替卡韦每天0.5 mg治疗HBeAg阳性C基因型慢性乙型肝炎患者,药物效力为99.970%(n=6),游离病毒半衰期为1.6 d(n=6),感染细胞半衰期为21.3 d(n=5).其中1例患者(例6)在随访至38周时发现有病毒学突破,与其他未发生病毒学突破的患者相比,其清除病毒的速度、药物效力、感染细胞消失的速度值较低,而游离病毒和感染细胞的半衰期较长.结论 抗病毒治疗过程中HBV DNA的二相下降模式可以由数学模型模拟,提示该模型对疗效具有一定的预测作用.

Viral dynamics during entecavtr therapy in patients with chronic hepatitis B

Objective To analyze the viral dynamics and clinical significance during the antiviral treatment by a mathematical model.Methods Six chronic hepatitis B patients were evaluated with a kinetic model(Neumann model)during dose of 0.5 mg/d oral entecavir.Blood samples were drawn for HBV DNA measurement at week 0,2,4,12,24.Non-linear modeling was used to fit individual patient data.Results The median effectiveness in blocking viral production was 99.970%(n=6).The median half-life of viral turn-over was 1.6 d(n=6).The median half-life of infected hepatocytes was 21.3 d(n=5).Compared with the other patients,the c(virions are cleared at a rate)、ε(effectiveness)、δ(infected cell are lost at a rate)value of one patient(eg.6)were all lower and the half-life of virus and infected cells were higher,and eg.6 developed viral break-through after 38 weeks of follow-up.Conclusions Viral load decay showed a biphasic pattern during entecavir therapy which can be described with a mathematical model.The model relates processes of viral infection and replication as well as drug efficacy to model parameters.It indicates the prediction of bio-mathematical model during antiviral treatment.