Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon
Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon
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DOI：
10.1053/jhep.2003.50218
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发表时间：
2003-06-01
期刊：
影响因子：
13.5
通讯作者：
Zeuzem, S
中科院分区：
文献类型：
--
作者：
Herrmann, E;Lee, JH;Zeuzem, S
病毒产生和清除之间的动态平衡是未经治疗的慢性丙型肝炎病毒感染的特征。开始抗病毒治疗后，可以使用数学模型观察和分析典型的病毒血症多相衰减。为了阐明利巴韦林与（聚乙二醇化）干扰素 α 联合使用时的抗病毒机制，我们研究了接受聚乙二醇干扰素 α-2a 加或不加利巴韦林以及标准干扰素 α-2b 加利巴韦林治疗 48 周的慢性丙型肝炎患者的动力学参数。在治疗前、治疗期间、治疗结束时和随访期间经常测量血清 HCV RNA。通过使用适当的病毒动力学模型，通过血清 HCV RNA 定量的非线性、最小二乘拟合得出动力学参数。所有治疗组的病毒衰变第一阶段（第 1 天）和病毒衰变第二阶段（第 2 至 21 天）相似。约7至28天后，在几名患者中观察到病毒衰变的第三阶段，并且与单独使用聚乙二醇干扰素α-2a治疗的患者相比，接受聚乙二醇干扰素α-2a加利巴韦林治疗的患者的该衰变阶段明显更快。第三阶段的衰退与病毒学治疗结束反应和持续病毒学反应相关。总之，初始病毒动力学的第三阶段衰减（可能代表治疗增强的感染细胞降解）在接受聚乙二醇干扰素 α-2a 加利巴韦林治疗的患者中更为明显。这一发现表明联合治疗可以更好地恢复患者的免疫反应。
A dynamic equilibrium between viral production and clearance characterizes untreated chronic hepatitis C viral infection. After initiating antiviral treatment, a typical multiphasic decay of viremia can be observed and analyzed using mathematical models. To elucidate the antiviral mechanism of ribavirin when used in combination with (pegylated) interferon alfa, we investigated kinetic parameters in patients with chronic hepatitis C treated with either peginterferon alpha-2a with or without ribavirin and standard interferon alpha-2b plus ribavirin for 48 weeks. Serum HCV RNA was measured frequently before, during, and at the end-of-treatment and the follow-up period. By using an appropriate model for viral dynamics, kinetic parameters were derived from nonlinear, least square fitting of serum HCV RNA quantifications. The first phase of viral decay (day 1) and the second phase of viral decay (days 2 to 21) were similar for all treatment groups. After about 7 to 28 days, a third phase of viral decay was seen in several patients, and this phase of decay was significantly faster in patients treated with peginterferon alpha-2a plus ribavirin compared with those treated with peginterferon alpha-2a alone. The decay of this third phase was associated with the virologic end-of-treatment response and sustained virologic response. In conclusion, the third-phase decay of initial viral kinetics, which may represent a treatment-enhanced degradation of infected cells, was more pronounced in patients treated with peginterferon alpha-2a plus ribavirin. This finding suggests that combination treatment leads to a better restoration of the patient's immune response.