多种丙型肝炎病毒核心抗原试剂用于临床感染筛查的多中心性能评价  

A multi-center performance evaluation of different hepatitis C virus core antigen assays for clinical infection screening

作　　者：杨瑞锋[1] 刘宁[2] 卞成蓉 刘娟 刘艳[1] 吴淑平 封波[1] 饶慧瑛[1] 李艳娇 李伯安 娄金丽[2] 陈红松[1] Yang Ruifeng;Liu Ning;Bian Chengrong;Liu Juan;Liu Yan;Wu Shuping;Feng Bo;Rao Huiying;Li Yanjiao;Li Bo′an;Lou Jinli;Chen Hongsong(Peking University People′s Hospital,Peking University Hepatology Institute,National Clinical Research Center for Infectious Disease,Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases,Beijing 100044,China;Clinical Laboratory Center,Beijing You′an Hospital,Capital Medical University,Beijing 100069,China;Department of Clinical Laboratory,the Fifth Medical Center,Chinese People′s Liberation Army(PLA)General Hospital,Beijing 100039,China;Research Center for Technologies in Nucleic Acid-Based Diagnostics and Therapeutics,Changsha 410000,China;Abbott Laboratories Trading(Shanghai)Co.,Ltd.Shanghai 200003,China)

机构地区：[1]北京大学人民医院,北京大学肝病研究所,国家感染性疾病临床医学研究中心分中心,丙型肝炎和肝病免疫治疗北京市重点实验室,北京100044 [2]首都医科大学附属北京佑安医院临床检验中心,北京100069 [3]解放军总医院第五医学中心检验科,北京100039 [4]感染性疾病及肿瘤基因诊断技术国家地方联合工程研究中心,长沙410000 [5]雅培贸易(上海)有限公司,上海200003

出　　处：《中华检验医学杂志》2023年第12期1305-1312,共8页Chinese Journal of Laboratory Medicine

摘　　要：目的开展一项真实世界的多中心、大样本量的临床研究,旨在全面考评3种商品化丙型肝炎病毒(HCV)核心抗原试剂的性能,为其用于HCV感染筛查提供数据支持,并为进一步提高试剂的敏感度和特异度提供思路。方法使用商品化HCV血清转换盘,以及来自2018年1月至2022年4月北京市3家三级甲等医院门诊和住院患者的常规传染病检测血清等不同类型的样本,评估3种HCV抗原试剂(Architect、Laibo和ChemClin)的最低检测限(LOD)、诊断敏感度和特异度等关键性能指标,并研究影响这些性能指标的因素。结果3种抗原试剂检测HCV感染的窗口期等于或稍长于RNA试剂的窗口期,但均短于抗体试剂的窗口期;丙型肝炎患者血清HCV核心抗原浓度与RNA水平相关(r=0.90,P<0.01)。1b型是我国最常见的基因型,Architect、Laibo和ChemClin抗原试剂的LOD分别相当于531、3698和4624 IU/ml的HCV RNA。纳入本研究的临床初治丙型肝炎患者HCV RNA水平呈偏态分布,≥95%患者病毒载量高于6166 IU/ml,因此3种HCV抗原试剂仍保持较高的诊断敏感度(94.33%~99.40%)。在54例感染HCV的免疫虚损患者(白血病患者)中,9%(5/54)感染者抗体为阴性,核心抗原则可检出全部感染者。3种抗原试剂的LOD均受HCV基因3型(尤其是3b亚型)毒株核心区氨基酸多态性的影响,Laibo和ChemClin 2种抗原试剂受血清中HCV抗体的影响,检测敏感度低。HCV抗原试剂诊断丙型肝炎的特异度为99.94%~99.98%,类风湿因子、自身抗体和其他不明干扰物可导致少量低值、“假阳性”抗原结果。结论3种HCV核心抗原试剂用于感染筛查有较高的敏感度和特异度,尤其适用于免疫虚损群体HCV感染的筛查,但试剂的灵敏度和特异性受多种因素影响,仍有提升空间。Objective We conducted a real-world multi-center clinical study with a large sample size to comprehensively evaluate the performance of three commercial hepatitis C virus(HCV)core antigen assays.The study aimed to evaluate the performance for their use in HCV infection screening,and to provide clues for further improving the sensitivity and specificity of the assays.Methods Key performance indicators including the lower limit of detection(LOD),diagnostic sensitivity,and specificity of three HCV antigen assays(the Architect,Laibo,and ChemClin HCV core antigen assays)were evaluated using commercial seroconversion panels reflecting early HCV infection and clinical routine serum samples of outpatients and inpatients from 3 tertiary hospitals from January 2018 to April 2022.Factors that affect the performance indicators were further investigated.Results The window period for detecting HCV infection with the three antigen assays was equal to or slightly longer than that of the RNA assay,but all are shorter than that of the anti-HCV assay.There was a good linear positive correlation between HCV core antigen and HCV RNA levels in treatment naive patients with hepatitis C(r=0.90,P<0.01).For the most common genotype 1b strain in China,the LOD of the three HCV assays were equivalent to 531 IU/ml(Architect),3,698 IU/mL(Laibo),and 4,624 IU/mL(ChemClin)HCV RNA,respectively.Due to the skewed distribution of HCV RNA levels in treatment-naive hepatitis C patients,more than 95%of the patients had viral loads higher than 6166 IU/ml.Therefore,the three HCV antigens assays still maintained a satisfactory diagnostic sensitivity(94.33%-99.40%).Among 54 immunodeficient patients(leukemia patients)with HCV infection,9%(5/54)had negative anti-HCV results,while the HCV antigen assays found all these infectors.Through further experiments,we revealed the amino acid polymorphism in the core region of genotype 3 strain impaired the sensitivity of all three HCV antigen assays.In addition,the sensitivity of the two domestic assays was impaired by

关 键 词：丙型肝炎病毒 核心抗原 筛查 性能评价 

分 类 号：R512.63[医药卫生—内科学]