Impact of ribavirin plasma level on sustained virological response in patients treated with pegylated interferon and ribavirin for chronic hepatitis C
Impact of ribavirin plasma level on sustained virological response in patients treated with pegylated interferon and ribavirin for chronic hepatitis C
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DOI：
10.1111/j.1365-2036.2009.04065.x
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发表时间：
2009-09-01
影响因子：
7.6
通讯作者：
De Ledinghen, V.
中科院分区：
文献类型：
--
作者：
Breilh, D.;Foucher, J.;De Ledinghen, V.
P>背景丙型肝炎病毒（HCV）感染治疗的主要目标是实现持续病毒学应答（SVR）。然而，利巴韦林的药理特性对SVR的影响尚未得到充分研究。目的通过一项前瞻性研究，评估接受聚乙二醇化干扰素(PEG-IFN)和利巴韦林治疗的HCV患者中利巴韦林血浆水平与SVR反应之间的关联。患者和方法接受PEG-IFN和利巴韦林治疗的患者在第4周和第12周时服用血浆利巴韦林剂量。在治疗结束后6个月评估SVR结果第4周时，HCV-RNA与利巴韦林血浆浓度C-min（r = -0.376，P = 0.002）和利巴韦林血浆浓度AUC（0 -> 12h）（r = -0.277，P = 0.018）之间存在很强的相关性。第12周时，HCV-RNA与利巴韦林血浆水平的C-min（r = -0.384，P < 0.0001）和利巴韦林血浆水平的AUC（0 -> 12h）（r = -0.257，P = 0.002）之间存在很强的相关性。在基因型 1 患者中，利巴韦林 AUC(0 → 12h) 和 C-min 与第 12 周时 HCV-RNA 阴性和 SVR 显着相关。在多重逻辑回归模型中，与基因1型患者的SVR独立相关的唯一因素是第12周时HCV-RNA阴性。结论与复发或无反应患者相比，持续病毒学应答者中利巴韦林在第4周和第12周时的C-min显着更高。然而，在基因1型患者中，第4周和第2周时的血浆利巴韦林水平与SVR无关。
P>BackgroundThe main goal of therapy in hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). However, the impact of the pharmacological properties of ribavirin on the SVR has not been fully investigated.AimTo evaluate, through a prospective study, the association between ribavirin plasma level and SVR response in HCV patients treated with pegylated interferon (PEG-IFN) and ribavirin.Patients and methodsPatients treated with PEG-IFN and ribavirin had plasmatic ribavirin dosage at weeks 4 and 12. SVR was evaluated 6 months after the end of treatment.ResultsAt week 4, a strong correlation was found between HCV-RNA and C-min of ribavirin plasma level (r = -0.376, P = 0.002) and AUC(0 -> 12h) of ribavirin plasma level (r = -0.277, P = 0.018). At week 12, a strong correlation was found between HCV-RNA and C-min of ribavirin plasma level (r = -0.384, P < 0.0001) and AUC(0 -> 12h) of ribavirin plasma level (r = -0.257, P = 0.002). In genotype 1 patients, AUC(0 -> 12h) ribavirin and C-min were significantly correlated with negative HCV-RNA at week 12 and SVR. In the multiple logistic regression model, the only factor independently associated with SVR in genotype 1 patients was negative HCV-RNA at week 12.ConclusionC-min of ribavirin at weeks 4 and 12 was significantly higher in sustained virological responders compared with relapser or nonresponder patients. However, in genotype 1 patients, plasma ribavirin level at weeks 4 and 2 was not associated with SVR.