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