Arnaud Clémence, Pradat Pierre, Spaziante Martina, Berthillon Pascale, Maynard Marianne, Taliani Gloria, Chemin Isabelle, Trépo Christian, Petit Marie-Anne
Centre de Recherche en Cancérologie de Lyon (CRCL), INSERM U1052/CNRS UMR5286, Lyon, France.
Antivir Ther. 2013;18(8):1027-32. doi: 10.3851/IMP2671. Epub 2013 Aug 15.
Unique serum anti-E1E2 antibodies were shown to be associated with spontaneous recovery or predictive of sustained virological response (SVR) in patients with chronic hepatitis C receiving pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. The objectives were to establish the relationship between pretreatment anti-E1E2 titres and HCV RNA kinetics during PEG-IFN/RBV therapy, and to examine whether the combined determination of interleukin (IL)28B rs12979860 and rs8099917, pretreatment inducible protein (IP)-10 levels and/or anti-E1E2 improved the prediction of SVR.
Sera from 26 treatment-naive consecutive HCV patients treated with PEG-IFN/RBV for 48 weeks were analysed. Serum anti-E1E2 titres and pretreatment IP-10 levels were measured by enzyme-linked immunosorbent assays. The IL28B variants were determined using genotyping real-time polymerase chain reaction method. Viral decline was measured at weeks (W) 4 and 12 and SVR assessed 6 months after the end of therapy.
Baseline anti-E1E2 titres were correlated with HCV RNA decline at W4 and W12 and were highly predictive of SVR with 100% of patients negative for anti-E1E2 failing to achieve SVR. Receiver operating characteristic curve analyses indicate that the best prediction of SVR (AUC 0.990) was obtained with the combination of anti-E1E2 and IP-10 levels. Predictive values were better than those obtained with IP-10 alone or in combination with IL28B variants.
Pretreatment serum anti-E1E2 response predicts HCV RNA clearance kinetics and treatment outcome. The combination of anti-E1E2 and IP-10 significantly improved the prediction of treatment response. This warrants further investigation and validation on larger cohorts of patients in the context of new therapeutic strategies.
在接受聚乙二醇干扰素/利巴韦林（PEG-IFN/RBV）治疗的慢性丙型肝炎患者中，独特的血清抗E1E2抗体与自发恢复相关或可预测持续病毒学应答（SVR）。目的是确定PEG-IFN/RBV治疗期间治疗前抗E1E2滴度与HCV RNA动力学之间的关系，并研究白细胞介素（IL）28B rs12979860和rs8099917、治疗前诱导蛋白（IP）-10水平和/或抗E1E2的联合检测是否能改善对SVR的预测。
分析了26例接受PEG-IFN/RBV治疗48周的初治连续HCV患者的血清。通过酶联免疫吸附测定法测量血清抗E1E2滴度和治疗前IP-10水平。使用基因分型实时聚合酶链反应方法确定IL28B变体。在第4周和第12周测量病毒载量下降，并在治疗结束后6个月评估SVR。
基线抗E1E2滴度与第4周和第12周的HCV RNA下降相关，并且对SVR具有高度预测性，100%抗E1E2阴性的患者未实现SVR。受试者操作特征曲线分析表明，抗E1E2和IP-10水平的组合对SVR的预测最佳（AUC 0.990）。预测值优于单独使用IP-10或与IL28B变体联合使用时获得的预测值。
治疗前血清抗E1E2反应可预测HCV RNA清除动力学和治疗结果。抗E1E2和IP-10的组合显著改善了对治疗反应的预测。这值得在新治疗策略背景下对更大患者队列进行进一步研究和验证。
