治疗前抗E1E2抗体状态有利于直接抗病毒治疗的疗效。

Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy.

作者信息

Virlogeux Victor, Berthillon Pascale, Bordes Isabelle, Larrat Sylvie, Crouy Stéphanie, Scholtès Caroline, Pradat Pierre, Maynard Marianne, Zoulim Fabien, Leroy Vincent, Chemin Isabelle, Trépo Christian, Petit Marie-Anne

机构信息

Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France; Service d'hépato-gastroentérologie, hôpital de la Croix-Rousse, hospices civils de Lyon, 69004 Lyon, France.

Centre de recherche en cancérologie de Lyon (CRCL), UMR Inserm 1052/CNRS 5286, 69003 Lyon, France; Université Claude-Bernard-Lyon 1, 69008 Lyon, France.

出版信息

Clin Res Hepatol Gastroenterol. 2018 Sep;42(4):313-318. doi: 10.1016/j.clinre.2018.02.002. Epub 2018 Mar 16.

Abstract

INTRODUCTION

Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy.

MATERIAL AND METHODS

We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients.

RESULTS

A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level.

CONCLUSIONS

The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure.

摘要

引言

抗E1E2抗体的存在以前与丙型肝炎病毒(HCV)的自发治愈相关,并且在初治或经治患者接受二联或三联疗法治疗前,可预测持续病毒学应答(SVR),无论HCV基因型如何。我们研究了基线时抗E1E2血清阳性率对接受直接抗病毒药物(DAA)治疗患者治疗反应的影响。

材料与方法

我们通过酶联免疫吸附测定(ELISA)法,对两组患者治疗开始时采集的血清样本进行抗E1E2抗体筛查:59例在DAA治疗结束时获得SVR的患者和44例DAA治疗后复发的患者。19例患者接受了利巴韦林(RBV)或聚乙二醇干扰素/利巴韦林与索磷布韦或达卡他韦的联合治疗,其他患者接受了不含干扰素的DAA±RBV治疗。在部分患者的治疗过程中,于不同时间点测量HCV病毒载量。

结果

观察到抗E1E2的存在与治疗前HCV病毒载量<6log10之间存在显著关联。基线时存在抗E1E2的患者中,70%实现了SVR,而在无抗E1E2的患者中,只有45%实现了SVR。相反,66%的DAA治疗失败患者基线时抗E1E2呈阴性。在多变量分析中,在对年龄、性别、纤维化分期、既往HCV治疗及丙氨酸氨基转移酶(ALT)水平等潜在混杂因素进行校正后,抗E1E2的存在与SVR显著相关。

结论

治疗开始时抗E1E2的存在是接受DAA治疗患者实现SVR的预测因素,在初始HCV病毒载量较低(<6log10)的患者中更有可能。基线时无抗E1E2可能预示DAA治疗失败。

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