Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy
Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy
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DOI：
10.1002/hep.510290626
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发表时间：
1999-06-01
期刊：
影响因子：
13.5
通讯作者：
Gibbs, CS
中科院分区：
文献类型：
--
作者：
Tsiang, M;Rooney, JF;Gibbs, CS
在最近的一项 II 期临床研究中，13 名慢性乙型肝炎感染患者每天接受 30 mg 阿德福韦酯治疗 12 周，血浆乙型肝炎病毒 (HBV)-DNA 水平中位下降 4.1-log(10)。治疗期间病毒载量的下降显示出双相动力学特征，该特征被建模以确定抑制病毒产生的功效，以及清除游离病毒和感染细胞损失的动力学常数。病毒产生被抑制，功效为 0.993 +/- 0.008，表明治疗期间只有 0.7% 的病毒产生持续存在。病毒载量下降的初始、较快阶段反映了 HBV 颗粒从血浆中的清除，半衰期为 1.1 +/- 0.3 天，相当于游离病毒的日周转率为 48%。病毒载量下降的第二个较慢阶段密切反映了受感染细胞损失的限速过程，半衰期为 18 +/- 7 天。从血浆中完全消除病毒或将其抑制至足以诱导血清转化的水平所需的治疗持续时间是游离病毒的半衰期、受感染细胞的半衰期以及抑制受感染细胞产生病毒的功效的函数。这些定量分析提供了 HBV 感染和治疗动态的更详细信息，可用于比较不同剂量和 HBV 复制抑制剂治疗 HBV 感染的疗效。
In a recent phase II clinical study, 13 chronic hepatitis B-infected patients treated daily with 30 mg adefovir dipivoxil for 12 weeks displayed a median 4.1-log(10) decrease in plasma hepatitis B virus (HBV)-DNA levels. The decline of viral load during therapy displayed a biphasic kinetic profile that was modeled to determine the efficacy of inhibition of viral production, as well as kinetic constants for the clearance of free virus and the loss of infected cells. Viral production was suppressed with an efficacy of 0.993 +/- 0.008, indicating that only 0.7% of viral production persisted during therapy. The initial, faster phase of viral load decline reflects the clearance of HBV particles from plasma with a half-life of 1.1 +/- 0.3 days, translating to a 48% daily turnover of the free virus. The second, slower phase of viral load decline closely mirrors the rate-limiting process of infected cell loss, with a half-life of 18 +/- 7 days. The duration of therapy required to completely eliminate the virus from plasma or suppress it to levels sufficient to induce seroconversion is a function of the half-life of the free virus, the half-life of infected cells, and the efficacy of inhibition of virus production from infected cells. These quantitative analyses provide a more detailed picture of the dynamics of HBV infection and therapy, and can be used to compare the efficacy of various doses and inhibitors of HBV replication for the treatment of HBV infections.