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基于PIVKA-Ⅱ、AFP和AFP-L3不同组合模式的肝细胞癌筛查策略探讨
Screening strategy for primary hepatocellular carcinoma based on different combinations of protein induced by vitamin K absence or antagonist-II, alpha-fetoprotein, and alpha-fetoprotein-L3
文章发布日期:2019年08月19日  来源:  作者:谢芳,于乐成,薛珠,等  点击次数:109次  下载次数:16次

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【摘要】:目的探讨血清PIVKA-Ⅱ、AFP和AFP异质体(AFP-L3)的优化组合对肝细胞癌(HCC)筛查诊断的敏感度和特异度。 方法收集2017年1月-2018年7月东部战区总医院全军肝病中心118例HCC患者和76例肝炎肝硬化住院患者的血清,分别检测PIVKA-Ⅱ、AFP和AFP-L3水平。比较各指标及其不同组合对HCC筛查的敏感度和特异度。偏态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验。分析PIVKA-Ⅱ、AFP及AFP-L3筛查HCC的效能,计算敏感度及特异度,并绘制受试者工作特征曲线(ROC曲线)。 结果HCC组PIVKA-Ⅱ、AFP水平均显著高于肝炎肝硬化组(Z值分别为7.80、3.80,P值均<0.001)。HCC组中PIVKA-Ⅱ、AFP、AFP-L3阳性比例均高于肝炎肝硬化组(χ2值分别为153.36、8397、168.82,P值均<0.001)。PIVKA-Ⅱ和AFP阳性率在HCC组差异无统计学意义(68.6% vs 67.8%, χ2=0.02,P>0.05),但在肝炎肝硬化组的差异有统计学意义(14.5% vs 51.3%, χ2=2337,P<0.001)。PIVKA-Ⅱ和AFP-L3阳性率在HCC组差异有统计学意义(68.6% vs 35.6%, χ2=25.83,P<0.001),但在肝炎肝硬化组差异无统计学意义(14.5% vs 9.2%,χ2=1.01,P>005)。AFP和AFP-L3阳性率在HCC组差异有统计学意义(67.8% vs 35.6%, χ2=24.50,P<0.001),在肝炎肝硬化组差异也有统计学意义(51.3% vs 9.2%, χ2=31.92,P<0.001)。PIVKA-Ⅱ筛查HCC的 ROC曲线下面积为0.832,显著高于AFP的0.662(P<0.01)和AFP-L3的0.656(P<0.01)。以PIVKA-Ⅱ>40 mAU/ml、AFP>10 ng/ml和AFP-L3>10%作为各自提示HCC可能的阳性界值,在ROC曲线中,PIVKA-Ⅱ和AFP的敏感度均为67.8%,高于AFP-L3的55%。PIVKA-Ⅱ的特异度为85.5%,高于AFP的48.7%和AFP-L3的60%。PIVKA-Ⅱ、AFP和AFP-L3均阳性时,对HCC的筛查敏感度仅为29.7%,但特异度提高至98.7%。PIVKA-Ⅱ+AFP联合筛查HCC的敏感度为55.9%,特异度为90.8%。PIVKA-Ⅱ+AFP-L3联合筛查HCC的敏感度为30.5%,特异度为98.7%;AFP+AFP-L3联合筛查HCC的敏感度为34.7%,特异度为93.4%。结论在除外抗凝剂和胆汁淤积等因素影响的前提下,血清 PIVKA-Ⅱ单项升高对HCC的筛查价值显著优于AFP 或AFP-L3单项升高。PIVKA-Ⅱ或AFP任一指标升高可显著提高对HCC的筛查敏感度,PIVKA-Ⅱ、AFP和AFP-L3三者或两两同时升高可显著提高对HCC的筛查特异度。
【Abstract】:ObjectiveTo investigate the sensitivities and specificities of different combinations of serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ), alpha-fetoprotein (AFP), and alpha-fetoprotein-L3 (AFP-L3) in the screening for primary hepatocellular carcinoma (HCC). MethodsSerum samples were collected from 118 patients with HCC and 76 patients with hepatitis or liver cirrhosis who were hospitalized in Liver Disease Center of PLA, General Hospital of Eastern Theater Command, from January 2017 to July 2018, and the serum levels of PIVKA-Ⅱ, AFP, and AFP-L3 were measured. The sensitivities and specificities of each individual indicator and their different combinations in HCC screening were calculated and compared. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups, and the chi-square test was used for comparison of categorical data between groups. The efficiency of PIVKA-Ⅱ, AFP, and AFP-L3 in HCC screening was analyzed, their sensitivities and specificities were calculated, and receiver operating characteristic (ROC) curves were plotted. ResultsThe HCC group had significantly higher levels of PIVKA-Ⅱ and AFP than the hepatitis/liver cirrhosis group (Z=7.80 and 3.80, both P<0.001). Compared with the hepatitis/liver cirrhosis group, the HCC group had a significantly higher proportion of patients with positive PIVKA-Ⅱ, AFP, or AFP-L3 (χ2=153.36, 83.97, and 168.82, all P<0.001). There was no significant difference between the positive rates of PIVKA-Ⅱ and AFP in the HCC group (686% vs 67.8%, χ2=0.02, P>0.05), while a significant difference was observed in the hepatitis/liver cirrhosis group (14.5% vs 51.3%, χ2=23.37, P<0.001). There was a significant difference between the positive rates of PIVKA-Ⅱ and AFP-L3 in the HCC group (68.6% vs 35.6%, χ2=25.83, P<0.001), while no significant difference was observed in the hepatitis/liver cirrhosis group (145% vs 9.2%, χ2=1.01, P>0.05). There was a significant difference between the positive rates of AFP and AFP-L3 in the HCC group (67.8% vs 35.6%, χ2=24.50, P<0.001) and the hepatitis/liver cirrhosis group (51.3% vs 9.2%, χ2=31.92, P<0.001). In HCC screening, PIVKA-Ⅱ had a significantly larger area under the ROC curve than AFP (0.832 vs 0.662, P<0.01) and AFP-L3 (0832 vs 0.656, P<0.01). With PIVKA-Ⅱ>40 mAU/ml, AFP>10 ng/ml, and AFP-L3>10% as the positive cut-off values for the possibility of HCC, both PIVKA-Ⅱ and AFP had a sensitivity of 67.8% in the ROC curve, which was significantly higher than the sensitivity of AFP-L3 (55%). PIVKA-Ⅱ had a significantly higher specificity than AFP (85.5% vs 48.7%) and AFP-L3 (85.5% vs 60%). In HCC screening, positive PIVKA-Ⅱ, AFP, and AFP-L3 had a sensitivity of 29.7% and a specificity of 98.7%; positive PIVKA-Ⅱ and AFP had a sensitivity of 55.9% and a specificity of 90.8%; positive PIVKA-Ⅱ and AFP-L3 had a sensitivity of 30.5% and a specificity of 98.7%; positive AFP and AFP-L3 had a sensitivity of 34.7% and a specificity of 93.4%. ConclusionIn the context of no influence from the factors including anticoagulants and cholestasis, elevated serum PIVKA-Ⅱ alone has a better value in HCC screening than elevated AFP or AFP-L3. The increase in PIVKA-Ⅱ or AFP significantly improves the sensitivity in HCC screening, and the increases in all or any two of PIVKA-Ⅱ, AFP- and AFP-L3 can significantly improve the specificity in HCC screening.
【关键字】:癌, 肝细胞; 维生素K缺乏或拮抗剂诱导的蛋白质Ⅱ; 甲胎蛋白类
【Key words】:carcinoma, hepatocellular; PIVKA-Ⅱ; alpha-fetoproteins
【引证本文】:XIE F, YU YC, XUE Z, et al. Screening strategy for primary hepatocellular carcinoma based on different combinations of protein induced by vitamin K absence or antagonist-II, alpha-fetoprotein, and alpha-fetoprotein-L3[J]. J Clin Hepatol, 2019, 35(9): 1975-1979. (in Chinese)
谢芳, 于乐成, 薛珠, 等. 基于PIVKA-Ⅱ、AFP和AFP-L3不同组合模式的肝细胞癌筛查策略探讨[J]. 临床肝胆病杂志, 2019, 35(9): 1975-1979.

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