慢性乙型肝炎恩替卡韦治疗过程中病毒动力学特点分析  

Viral dynamics during entecavir therapy in patients with chronic hepatitis IS

作　　者：姚碧莲[1] 张欣欣[1] 杨劲[2] 于德敏[1] 张东华[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025 [2]中国科学院上海生命科学研究院计算生物学研究所

出　　处：《中华传染病杂志》2009年第6期338-342,共5页Chinese Journal of Infectious Diseases

基　　金：国家973项目基金资助项目（2005CB523104）;国家十一五重大专项资助项目（2008ZX10202）

摘　　要：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0．5mg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1．6d（n=6），感染细胞半衰期为21．3d（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HBVDNA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。Objective To analyze the viral dynamics and clinical significance during the antiviral treatment by a mathematical mode[. 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 was21.3 d （n= 5）. Compared with the other patients, the c（virions are cleared at a rate）.s （effectiveness）.3（infeeted cell are lost at a rate） value of one patient （eg. 6） were all lower and the halblife 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.

关 键 词：肝炎 乙型 慢性 抗病毒药 动力学 模型 理论 恩替卡韦 DNA 病毒 

分 类 号：R512.62[医药卫生—内科学] R512.91[医药卫生—临床医学]