Neumann A U, Lam N P, Dahari H, Gretch D R, Wiley T E, Layden T J, Perelson A S
Department of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.
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 (t1/2) 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 t1/2 = 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.
为了更好地理解丙型肝炎病毒的动态变化以及α-2b干扰素（IFN）的抗病毒作用，利用数学模型分析了23例患者在治疗期间的病毒载量下降情况。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，每日剂量为500万、1000万和1500万国际单位时，阻断效率分别为81%、95%和96%。估计病毒粒子的半衰期（t1/2）平均为2.7小时，治疗前每天产生和清除10¹²个病毒粒子。估计的受感染细胞死亡率在患者之间存在很大差异（相应的t1/2 = 1.7至70天），与基线病毒载量呈负相关，与丙氨酸氨基转移酶水平呈正相关。快速死亡率预示着在3个月时通过聚合酶链反应无法检测到病毒。这些发现表明，丙型肝炎病毒感染具有高度动态性，早期监测病毒载量有助于指导治疗。
