肝癌筛查技术准确性的Meta分析

The accuracy of screening technologies for liver cancer:a meta-analysis

目的系统评价不同肝癌筛查技术的准确性,为人群筛查和早期诊断提供依据。方法计算机检索Pub Med、The Cochrane Library、EMbase、Web of Science、CNKI、Wan Fang Data、CBM和VIP,搜集肝癌筛查的诊断性试验,检索时限均从1980年1月至2017年12月。由2名研究员独立筛选文献、提取资料,并评价纳入研究的偏倚风险后,采用Meta-Disc1.4软件行Meta分析。结果最终纳入54个研究,包括47 728例患者。Meta结果显示,单独血清甲胎蛋白筛查(AFP)不同截断值(20 ng/m L、200 ng/m L和400 ng/m L)筛查肝癌的Sen_(合并)分别为0.71[95%CI(0.70,0.72)]、0.57[95%CI(0.56,0.59)]和0.43[95%CI(0.41,0.45)],Spe_(合并)分别为0.92[95%CI(0.92,0.93)]、0.95[95%CI(0.94,0.96)]和0.95[95%CI(0.94,0.96),+LR_(合并)分别为5.65[95%CI(4.37,7.30)]、13.24[95%CI(4.25,41.22)]和11.39[95%CI(4.01,32.35)],–LR_(合并)分别为0.35[95%CI(0.31,0.39)]、0.38[95%CI(0.29,0.52)]和0.49[95%CI(0.39,0.62)],DOR分别为17.23[95%CI(12.26,24.20)]、33.79[95%CI(12.65,90.24)]和24.41[95%CI(9.23,64.53)];单独肝脏超声筛查肝癌的Sen_(合并)、Spe_(合并)、+LR_(合并)、–LR_(合并)、DOR分别为0.65[95%CI(0.62,0.69)]、0.97[95%CI(0.97,0.97)]、16.48[95%CI(9.55,28.42)]、0.27[95%CI(0.18,0.42)]和64.54[95%CI(30.16,138.11)];AFP-20联合超声筛查肝癌的Sen_(合并)、Spe_(合并)、+LR_(合并)、–LR_(合并)、DOR分别为0.96[95%CI(0.94,0.98)]、0.96[95%CI(0.96,0.96)]、10.76[95%CI(2.62,44.27)]、0.07[95%CI(0.02,0.22)]和160.59[95%CI(31.61,816.03)]。结论单独血清甲胎蛋白筛查以20 ng/m L为阈值时诊断价值最佳,其联合超声检查的筛查方案,可大幅提高诊断敏感度,适用于高危人群筛查。

Objectives To evaluate the accuracy of liver cancer screening techniques to inform screening intervention and early diagnosis. Methods We searched Pub Med, The Cochrane Library, EMbase, Web of Science,CNKI, Wan Fang Data, CBM, VIP databases to collect relevant diagnostic accuracy studies of screening technologies for liver cancer from January 1980 to December 2017. Two reviewers independently screened the literature, extracted the data and assessed the risk of bias of included studies. Then meta-analysis was performed by using Meta-Disc 1.4 software.Results A total of 54 publications with 47 728 individuals were included. In terms of pooled sensitivity from the metaanalysis, it was estimated as 0.71（95%CI 0.70 to 0.72）, 0.57（95%CI 0.56 to 0.59） and 0.43（95%CI 0.41 to 0.45）; the pooled specificity was estimated as 0.92（95%CI 0.92 to 0.93）, 0.95（95%CI 0.94 to 0.96） and 0.95（95%CI 0.94 to 0.96）; the pooled positive likelihood ratio was 5.65（95%CI 4.37 to 7.30）, 13.24（95%CI 4.25 to 41.22） and 11.39（95%CI 4.01 to 32.35）; the pooled negative likelihood ratio was 0.35（95%CI 0.31 to 0.39）, 0.38（95%CI 0.29 to 0.52） and 0.49（95%CI 0.39 to 0.62）;the diagnosis odds ratio was 17.23（95%CI 12.26 to 24.20）, 33.79（95%CI 12.65 to 90.24） and 24.41（95%CI 9.23 to 64.53）for AFP alone with cut-off of 20, 200 and 400 ng/mL, respectively. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnosis odds ratio were 0.65（95%CI 0.62 to 0.69）, 0.97（95%CI 0.97 to 0.97）, 16.48（95%CI 9.55 to 28.42）, 0.27（95%CI 0.18 to 0.42） and 64.54（95%CI 30.16 to 138.11） for ultrasound examination alone. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnosis odds ratio were 0.96（95%CI0.94 to 0.98）, 0.96（95%CI 0.96 to 0.96）, 10.76（95%CI 2.62 to 44.27）, 0.07（95%CI 0.02 to 0.22） and 160.59（95%CI 31.61 to816.03） for the combined strategy. Conclusion For liver cancer screening technologies, the overall accuracy of serum AFP test alone is the optimum at cut-off of 20 ng/mL, and the sensitivity increased substantially when combined with ultrasound examination.