A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease.
A mathematical model of hepatitis C virus dynamics in patients with high baseline viral loads or advanced liver disease.
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DOI：
10.1053/j.gastro.2008.12.060
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发表时间：
2009-04
期刊：
影响因子：
29.4
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
Dahari H;Layden-Almer JE;Kallwitz E;Ribeiro RM;Cotler SJ;Layden TJ;Perelson AS
基线丙型肝炎病毒RNA水平（bHCV-RNA）>6 log IU/ml或肝硬化的患者持续病毒学应答（SVR）的可能性降低。我们使用一个数学模型来研究bHCV-RNA、肝硬化和SVR之间的关系，该模型包括关键药物疗效（εc;药物清除HCV所需的疗效）、感染率常数（β）和HCV感染肝细胞的百分比（π）。基线因素和SVR之间的关系在1,000例HCV感染患者中进行了评估，这些患者是通过随机分配真实的宿主和病毒动力学参数产生的。将模型预测与170例非血栓患者和75例血栓患者的临床数据进行了比较。β和病毒产生率（p）的选择范围导致bHCV-RNA水平与美国患者中观察到的分布一致。使用这些β和p值，较高的bHCV-RNA水平导致较高的εc，从而导致较低的SVR率。另外，较高的β值导致较低的bHCV-RNA水平，但较高的π和εc，预测较低的SVR率。肝硬化患者的bHCV-RNA水平低于非肝硬化患者（p=0.013），且更多患者的bHCV-RNA水平<6 log IU/ml（p<0.001）。即使是bHCV-RNA水平较低的阿尔茨海默病患者，SVR率也较低。β增加可以解释在阿尔茨海默病患者中观察到的结果。我们的模型预测，较高的bHCV-RNA水平导致较高的εc，降低了实现SVR的机会;肝硬化患者的SVR率较低，因为大π值，由肝细胞感染率增加引起。
Patients with baseline hepatitis C virus-RNA levels (bHCV-RNA) >6 log IU/ml or cirrhosis have a reduced probability of a sustained-virological response (SVR). We examined the relationship between bHCV-RNA, cirrhosis and SVR using a mathematical model that includes the critical-drug efficacy (εc; the efficacy required for a drug to clear HCV), the infection-rate constant (β) and the percentage of HCV-infected hepatocytes (π). The relationship between baseline factors and SVR was evaluated in 1,000 in silico HCV-infected patients, generated by randomly assignment of realistic host and viral kinetic parameters. Model predictions were compared with clinical data from 170 non-cirrhotic and 75 cirrhotic patients. The ranges chosen for β and the viral production rate (p) resulted in bHCV-RNA levels that were in agreement with the distribution observed in US patients. Using these β and p values, higher bHCV-RNA levels led to higher εc, resulting in lower SVR rates. Alternatively, higher β values resulted in lower bHCV-RNA levels but higher π and εc, predicting lower rates of SVR. Cirrhotic patients had lower bHCV-RNA levels than non-cirrhotic patients (p=0.013) and more had bHCV-RNA levels <6 log IU/ml (p<0.001). Even cirrhotic patients with lower bHCV-RNA levels had lower SVR rates. An increase in β could explain the results observed in cirrhotic patients. Our model predicts that higher bHCV-RNA levels lead to higher εc, reducing the chance of achieving SVR; cirrhotic patients have lower SVR rates because of large π values, caused by increased rates of hepatocyte infection.
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影响因子：
4.3
作者：
Medeiros-Filho, Jose Eymard;Guedes de Carvalho Mello, Isabel Maria Vicente;Carrilho, Flair Jose
通讯作者：
Carrilho, Flair Jose
影响因子：
64.8
作者：
Dixit, NM;Layden-Almer, JE;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
158.5
作者：
McHutchison, JG;Gordon, SC;Albrecht, JK
通讯作者：
Albrecht, JK
影响因子：
13.5
作者：
Dahari, Harel;Ribeiro, Ruy M.;Perelson, Alan S.
通讯作者：
Perelson, Alan S.
影响因子：
2
作者：
Dahari, Harel;Lo, Arthur;Perelson, Alan S.
通讯作者：
Perelson, Alan S.