Colombatto Piero, Civitano Luigi, Oliveri Filippo, Coco Barbara, Ciccorossi Pietro, Flichman Diego, Campa Mario, Bonino Ferruccio, Brunetto Maurizia Rossana
UO Gastroenterologia ed Epatologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
Antivir Ther. 2003 Dec;8(6):519-30.
Standard models simulate the dynamics of hepatitis C virus (HCV) infection using HCV RNA kinetics and show a correlation between the clearance of infected hepatocytes and response to interferon. However, they are unable to predict whether the response will be maintained. The aim of our work was to identify criteria by which sustained responses may be predicted and defined.
In our model the clearance rate of infected cells is a function of their number and the baseline rate is computed by the alanine aminotransferase (ALT) kinetics during the first month of therapy. We simulated the variations of viral and infected cell loads in 31 consecutive patients treated with IFN-alpha2b 3-5 MU every other day, with or without ribavirin, for 6 or 12 months depending on HCV genotype.
At baseline the computed (in 28 of 31 cases) percentage of infected cells was lower in seven sustained responders (mean: 11.7%, range: 1-24.6%) than in 14 transient responders (mean: 28.2%, range: 7.4-75.5%) and in seven non-responders (mean: 41%, range: 8.8-86%) (P=0.036). At the end of therapy the computed infected cell number was <100 cells/ml of extracellular fluid in all sustained responders (mean: 18.4, range: 1.7-48), in three transient responders (mean: 3500, range: 1.52-17500) and in none non-responders (mean: 28500, range: 1200-96000) (P=0.003). Overall of 10 patients with less than 100 infected cells/ml at the end of therapy seven (six had combination therapy) showed sustained response. All three relapsers received interferon monotherapy.
The analysis of infected cells dynamics using the new model might be useful to tailor treatment duration in patients with combination therapy.
标准模型利用丙型肝炎病毒（HCV）RNA动力学模拟HCV感染的动态变化，并显示出受感染肝细胞的清除与对干扰素的反应之间存在相关性。然而，它们无法预测反应是否会持续。我们研究的目的是确定能够预测和定义持续反应的标准。
在我们的模型中，受感染细胞的清除率是其数量的函数，基线率通过治疗第一个月期间的丙氨酸氨基转移酶（ALT）动力学来计算。我们模拟了31例连续患者的病毒和受感染细胞载量变化，这些患者根据HCV基因型，每隔一天接受3 - 5MU的α-干扰素2b治疗，联合或不联合利巴韦林，治疗6或12个月。
在基线时，7例持续反应者（平均：11.7%，范围：1 - 24.6%）计算得出的（31例中的28例）受感染细胞百分比低于14例短暂反应者（平均：28.2%，范围：7.4 - 75.5%）和7例无反应者（平均：41%，范围：8.8 - 86%）（P = 0.036）。治疗结束时，所有持续反应者（平均：18.4，范围：1.7 - 48）每毫升细胞外液中计算得出的受感染细胞数<100个细胞，3例短暂反应者（平均：3500，范围：1.52 - 17500）和无反应者均无（平均：28500，范围：1200 - 96000）（P = 0.003）。治疗结束时每毫升受感染细胞数少于100个的10例患者中，7例（6例接受联合治疗）显示出持续反应。所有3例复发者均接受干扰素单药治疗。
使用新模型分析受感染细胞动力学可能有助于确定联合治疗患者的治疗持续时间。
