Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy
Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy
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DOI：
10.1126/science.282.5386.103
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发表时间：
1998-10-02
期刊：
影响因子：
56.9
通讯作者：
Perelson, AS
中科院分区：
文献类型：
--
作者：
Neumann, AU;Lam, NP;Perelson, AS
为了更好地了解丙型肝炎病毒的动态和干扰素- α -2b （IFN）的抗病毒作用，用数学模型分析了23例患者在治疗期间的病毒下降情况。分析表明，IFN的主要初始作用是阻断病毒粒子的产生或释放，每日剂量分别为5,1000万和1,500万国际单位时，阻断率分别为81%，95%和96%。估计的病毒粒子半衰期（t(1/2)）平均为2.7小时，预处理每天产生和清除10（12）个病毒粒子。估计的感染细胞死亡率在患者间表现出很大的差异（对应的t(1/2) = 1.7至70天），与基线病毒载量呈负相关，与丙氨酸转氨酶水平呈正相关。快速死亡率可预测3个月时聚合酶链反应检测不到病毒。这些发现表明，丙型肝炎病毒感染是高度动态的，早期监测病毒载量有助于指导治疗。
To better understand the dynamics of hepatitis C virus and the antiviral effect of interferon-alpha-2b (IFN), viral decline in 23 patients during therapy was analyzed with a mathematical model. The analysis indicates that the major initial effect of IFN is to block virion production or release, with blocking efficacies of 81, 95, and 96% for daily doses of 5, 10, and 15 million international units, respectively. The estimated virion half-life (t(1/2)) was, on average, 2.7 hours, with pretreatment production and clearance of 10(12) virions per day. The estimated infected cell death rate exhibited large interpatient variation (corresponding t(1/2) = 1.7 to 70 days), was inversely correlated with baseline viral load, and was positively correlated with alanine aminotransferase levels. Fast death rates were predictive of virus being undetectable by polymerase chain reaction at 3 months. These findings show that infection with hepatitis C virus is highly dynamic and that early monitoring of viral load can help guide therapy.