血清异常凝血酶原用于辅助诊断肝细胞癌临床价值的评估:一项基于中国人群的多中心病例对照研究  

Assessment of the clinical value with the application of serum abnormal prothrombin for auxiliary diagnosis of hepatocellular carcinoma:a multicenter Chinese population-based case-control study

作　　者：梁携儿[1] 程黎明[2] 许颂霄 张钧[4] 陈红松[5] 濮存莹 樊蓉[1] 侯金林[1] Liang Xieer;Cheng Liming;Xu Songxiao;Zhang Jun;Chen Hongsong;Pu Cunying;Fan Rong;Hou Jinlin(Hepatology Unit and Department of Infectious Diseases,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Department of Laboratory Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Clinical Laboratory,Zhejiang Cancer Hospital,Hangzhou 310006,China;Department of Clinical Laboratory,Sir Run Run Shaw Hospital,Zhejiang University,School of Medicine,Hangzhou 310016,China;Peking University People's Hospital,Peking University Hepatology Institute,Beijing 100044,China;Roche Diagnostics(Shanghai)Limited,Medical and Scientific Affairs,Shanghai 200126,China)

机构地区：[1]南方医科大学南方医院感染内科暨肝病中心,广州510515 [2]华中科技大学同济医学院附属同济医院检验科,武汉430030 [3]浙江省肿瘤医院检验科,杭州310006 [4]浙江大学医学院附属邵逸夫医院检验科,杭州310016 [5]北京大学人民医院北京大学肝病研究所,北京100044 [6]罗氏诊断产品(上海)有限公司医学科学事务部,上海200126

出　　处：《中华肝脏病杂志》2024年第7期650-656,共7页Chinese Journal of Hepatology

基　　金：国家重点研发计划(2022YFC2304800,2022YFC2303600)。

摘　　要：目的综合评估Elecsys血清异常凝血酶原(PIVKA-Ⅱ)检测试剂在中国人群中辅助诊断肝细胞癌(HCC)的临床价值。方法研究采用多中心病例-对照设计,连续收集首次确诊且未经治疗的HCC患者样本、良性肝病患者样本和干扰性样本进行Elecsys PIVKA-Ⅱ与甲胎蛋白(AFP)检测,并对受试者的多项临床信息进行汇总分析。计算特定阳性截断值下PIVKA-Ⅱ(21.29 ng/ml)和AFP(400 ng/ml)用于HCC诊断的效能。采用Kruskal-Wallis检验或受试者操作特征曲线进行统计学分析。结果最终在5家中心共纳入448例受试者,其中包括185例HCC病例。以良性肝病组为对照组时,PIVKA-Ⅱ的诊断灵敏度和准确率均高于AFP:84.86%对比30.81%和89.01%对比63.66%,而特异度略低。敏感性分析显示在该特定阳性截断值下,PIVKA-Ⅱ的临床性能在AFP阴性受试者亚组、不同病因亚组及多个巴塞罗那癌症分期的HCC患者亚组(含早期HCC)中的灵敏度均>80%。同时,PIVKA-Ⅱ的受试者操作特征曲线下面积亦略高于AFP(0.9200对比0.8809)。结论Elecsys PIVKA-Ⅱ在中国人群中的临床性能良好且稳定,有潜力改善临床AFP阴性HCC诊断和早期HCC监测中的漏诊现状以进一步提升中国人群HCC精准辅助诊断效率。ObjectiveTo comprehensively evaluate the clinical value of Elecsys serum abnormal prothrombin(PIVKA-Ⅱ)test reagent for auxiliary diagnosis of hepatocellular carcinoma(HCC)in the Chinese population.MethodsA multicenter case-control design was used in the study.Samples from patients with first-time confirmed,diagnosed,and untreated HCC,benign liver disease and interfering controls were collected continuously.Elecsys PIVKA-II and alpha-fetoprotein(AFP)were tested for analysis.Various clinical details of the subjects were collected and analyzed.The efficacy of PIVKA-II(21.29 ng/ml)and AFP(400 ng/ml)for HCC diagnosis was calculated at specific positive cut-off values.Statistical analysis was performed using the Kruskal-Wallis test or receiver operating characteristic curve.ResultsA total of 448 subjects were eventually enrolled from five centers,including 185 HCC cases.PIVKA-II had a higher diagnostic sensitivity and accuracy than AFP(84.86%vs.30.81%and 89.01%vs.63.66%)when the benign liver disease group was used as the control group,while the specificity was slightly lower.A sensitive analysis showed that PIVKA-II had a sensitivity of>80%at this specific positive cut-off value in the subgroup of AFP-negative subjects,patients with different etiologies,and HCC patients with multiple Barcelona Clinic liver cancer stages(including early-stage HCC).At the same time,the PIVKA-II subject had a slightly higher area under the receiver operating characteristic curve than the AFP(0.9200 vs.0.8809).ConclusionThe clinical efficacy of Elecsys PIVKA-Ⅱis good and stable in the Chinese population.Additionally,it has the clinical potential to improve the current missed diagnosis status of AFP-negative HCC and HCC monitoring at an early stage,as well as the effectiveness of accuracy promotion for HCC auxiliary diagnosis in China.

关 键 词：肝细胞癌 甲胎蛋白 血清异常凝血酶原 早期原发性肝癌 截断值 诊断 

分 类 号：R735.7[医药卫生—肿瘤]