Canini Laetitia, DebRoy Swati, Mariño Zoe, Conway Jessica M, Crespo Gonzalo, Navasa Miquel, D'Amato Massimo, Ferenci Peter, Cotler Scott J, Forns Xavier, Perelson Alan S, Dahari Harel
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.
Antivir Ther. 2015;20(2):149-55. doi: 10.3851/IMP2806. Epub 2014 Jun 10.
HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease.
Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [εmax]) was fitted to viral kinetic data.
Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [se]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [se=0.18/day]). HCV-infected cell loss rate (δ [se]=0.62/day [0.05/day]) was high and similar among groups.
The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.
对于等待肝移植的失代偿期肝硬化患者，尚未进行抗病毒治疗期间的丙型肝炎病毒（HCV）动力学分析和建模。在此，根据肝病严重程度，将三组接受每日静脉注射水飞蓟宾（SIL）单药治疗7天的患者的病毒和宿主参数进行了比较。
数据来自25例患者，其中12例非肝硬化患者，8例代偿期肝硬化患者和5例失代偿期肝硬化患者。将具有随时间变化的SIL有效性（从0至最终有效性[εmax]）的标准双相模型拟合至病毒动力学数据。
基线病毒载量和年龄与肝病严重程度显著相关（P<0.0001）。大多数患者观察到双相病毒下降，肝病较轻的患者第一阶段下降幅度更大。εmax与肝病严重程度增加显著相关（P≤0.032）（非肝硬化患者εmax[标准误]=0.86[0.05]，代偿期肝硬化患者εmax=0.69[0.06]，失代偿期肝硬化患者εmax=0.59[0.1]）。各组间第二阶段下降斜率无显著差异（平均1.88±0.15 log10 IU/ml/周，P=0.75），SIL有效性变化率（k=2.12/天[标准误=0.18/天]）亦是如此。HCV感染细胞损失率（δ[标准误]=0.62/天[0.05/天]）较高且各组间相似。
HCV感染细胞的高损失率表明，足够剂量和疗程的SIL可能在晚期肝病中实现病毒抑制。
