Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing
Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing
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DOI：
10.1016/j.jhep.2010.04.024
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发表时间：
2010-10-01
影响因子：
25.7
通讯作者：
Dore, Gregory J.
中科院分区：
文献类型：
--
作者：
Cheng, Wendy S. C.;Roberts, Stuart K.;Dore, Gregory J.
背景和目标：CHARIOT研究了慢性丙型肝炎病毒（HCV）治疗反应的纤维化阶段的影响，CHARIOT研究了高剂量聚乙二醇干扰素α-2a（PEG-IFN α-2a）诱导治疗初治的基因型1 infecties.Methods：896例患者按1：1的比例随机分配至360 μ g（n = 448）或180 μ g（n = 448）PEG-IFN α-2a每周一次，RBV 1000-1200 mg/天，持续12周，随后是36周的180 μ g PEG-IFN α-2a每周一次加RBV 1000-1200 mg/天。在第4、8、12、24、48周（治疗结束）和治疗后24周（持续病毒学应答，SVR）评估病毒学应答。如前所述，诱导组（53%）和标准组（50%）的SVR无显著差异，因此将研究人群合并用于分析SVR和复发。F4（10%）（p < 0.0001）。F3/4患者的早期病毒学应答较低，包括快速病毒学应答（RVR）（F3/4和F0-2分别为21%和3/4%）（p = 0.0072），RVR阳性预测值也较低（63%和80%）。病毒学复发率在早期疾病阶段相似（F0，16%; F1，23%; F2，26%），但在晚期纤维化中显著增加（F3，50%; F4，80%）（p < 0.0001）。治疗组内F3/4和F0-2的患者在第4、8、12和24周的累积PEG-IFN α-2a和利巴韦林剂量相似。结论：基因1型丙型肝炎晚期肝纤维化患者的病毒学应答低不能用累积PEG-IFN和利巴韦林剂量不足来解释。(C)2010年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: The impact of fibrosis stage on chronic hepatitis C virus (HCV) treatment response was explored in CHARIOT, a study of high dose peginterferon alfa-2a (PEG-IFN alpha-2a) induction therapy in treatment naive genotype 1 infection.Methods: Eight hundred and ninety-six patients were randomised 1:1 to 360 mu g (n = 448) or 180 mu g (n = 448) PEG-IFN alpha-2a weekly with RBV 1000-1200 mg/day for 12 weeks followed by 36 weeks of 180 mu g PEG-IFN alpha-2a weekly plus RBV 1000-1200 mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (sustained virological response, SVR). As previously reported, there was no significant difference in SVR in the induction (53%) and standard (50%) arms, therefore the pooled study population was used for analysis of SVR and relapse.Results: A marked step-wise decline in SVR was evident by fibrosis stage: F0 (70%); F1 (60%); F2 (51%); F3 (31%); F4 (10%) (p < 0.0001). Early virological responses were lower among F3/4 patients, including rapid virological response (RVR) (21% vs. 34% for F3/4 and F0-2, respectively) (p = 0.0072), and the RVR positive predictive value was also lower (63% vs. 80%). Virological relapse rates were similar in early disease stages (F0, 16%; F1, 23%; F2, 26%), but increased markedly in advanced fibrosis (F3, 50%; F4, 80%) (p < 0.0001). Cumulative PEG-IFN alpha-2a and ribavirin doses were similar among patients with F3/4 and F0-2 within treatment arms through week 4, 8, 12, and week 24.Conclusions: Low virological response in hepatitis C genotype 1 patients with advanced fibrosis is not explained by inadequate cumulative PEG-IFN and ribavirin doses. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.