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甲胎蛋白和甲胎蛋白异质体比率(AFP-L3%)对HBV相关早期肝细胞癌的诊断效能分析

唐宇雁 谢仕斌 朱建芸

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甲胎蛋白和甲胎蛋白异质体比率(AFP-L3%)对HBV相关早期肝细胞癌的诊断效能分析

DOI: 10.3969/j.issn.1001-5256.2023.11.014
伦理学声明:本研究方案于2023年1月11日经由中山大学附属第三医院伦理委员会审批,批号:Ⅱ2022-008-01。所有患者均知情同意。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:唐宇雁负责课题设计,收集数据,资料分析,撰写论文;谢仕斌负责课题设计,修改论文;朱建芸负责拟定写作思路,指导撰写文章并最后定稿。
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    ‍朱建芸, 13719366255@139.com (ORCID: 0000-0002-2875-7932)

Diagnostic efficacy of alpha-fetoprotein and alpha-fetoprotein L3% in hepatitis B virus-related early-stage hepatocellular carcinoma

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  • 摘要:   目的  探讨甲胎蛋白(AFP)、AFP异质体L3(AFP-L3)在HBV相关早期肝细胞癌(HCC)中的诊断效能及最佳截断值。  方法  纳入2019年1月—2022年7月在中山大学附属第三医院就诊的首次诊断且尚未治疗的HBV相关HCC患者(HCC组)共1 080例(其中中国肝癌分期Ⅰ‍a~Ⅱa期肝癌620例),346例慢性乙型肝炎患者(CHB组)和293例HBV相关肝硬化患者(LC组)为对照组,分析AFP和AFP-L3%筛查HBV相关早期HCC的诊断效能,包括灵敏度、特异度、受试者工作特征曲线下面积(AUC)等。偏态分布的计量资料两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni法。  结果  HCC组AFP、AFP-L3%水平显著高于CHB组和LC组(H分别为542.479、418.974,P值均<0.001)。在早期HCC中,AFP和AFP-L3%最佳截断值分别为8.7 ng/mL和5%,AFP单用时AUC最高,为0.816,灵敏度和特异度分别为66.9%、85.1%;联合使用AFP-L3%与单用AFP的AUC无明显差异(Z=0.609,P=0.543),但均显著高于单用AFP-L3%(AFP vs AFP-L3%:Z=8.173,P<0.001;AFP+AFP-L3% vs AFP-L3%:Z=8.802,P<0.001)。  结论  AFP对HBV相关早期HCC有较好的诊断价值,并且优于AFP-L3%,为了提高早期HCC的检出率,应该下调AFP的筛查截断值。

     

  • 图  1  AFP、AFP-L3%单独及联合诊断总体HCC的ROC曲线

    Figure  1.  ROC curve of AFP, AFP-L3% alone and combined about the diagnosis of total HCC

    图  2  AFP、AFP-L3%单独及联合诊断早期HCC的ROC曲线

    Figure  2.  ROC curve of AFP, AFP-L3% alone and combined about diagnosis of CNLC early stage HCC

    表  1  3组患者临床基线特点及AFP、AFP-L3、AFP-L3%的比较

    Table  1.   Comparison of clinical baseline characteristics and distribution of AFP, AFP-L3 and AFP-L3% in three groups

    项目 CHB组(n=346) LC组(n=293) HCC组(n=1 080) 统计值 P
    年龄(岁) 43.0(34.8~50.0) 52.0(45.0~59.0) 55.5(48.0~63.0) H=248.327 <0.001
    男/女(例) 249/97 236/57 969/111 χ2=67.783 <0.001
    HBeAg阳性1)[例(%)] 86/333(25.8) 47/283(16.6) 229/1 068(21.4) χ2=20.143 <0.001
    HBV DNA≥100 IU/mL1)[例(%)] 110/341(32.3) 68/290(23.4) 569/1 029(55.3) χ2=136.770 <0.001
    ALT(U/L) 24.0(18.0~30.0) 25.0(19.0~31.0) 33.0(24.0~51.0) H=208.268 <0.001
    Child-Pugh分级(A/B/C,例) 333/13/0 183/86/24 848/195/37 χ2=115.502 <0.001
    AFP(ng/mL) 3.2(2.4~4.7) 3.9(2.4~7.2) 25.8(6.7~176.6) H=542.497 <0.001
    AFP-L3(ng/mL) 0.6(0.6~0.6) 0.6(0.6~0.6) 2.7(0.6~23.4) H=456.749 <0.001
    AFP-L3(%) 5.0(5.0~5.0) 5.0(5.0~5.0) 9.0(5.0~14.2) H=418.974 <0.001
    注:1)部分指标的观察例数有缺失,原因为部分患者住院期间未能完善相关检查。
    下载: 导出CSV

    表  2  对照组与早期HCC组AFP、AFP-L3、AFP-L3%水平比较

    Table  2.   Comparison of AFP, AFP-L3 and AFP-L3% levels between the control group and the early stage HCC

    项目 对照组(n=639) 早期HCC组(n=620) Z P
    AFP(ng/mL) 3.5(2.4~5.9) 18.7(5.5~121.4) -19.381 <0.001
    AFP-L3(ng/mL) 0.6(0.6~0.6) 1.9(0.6~14.7) -18.352 <0.001
    AFP-L3(%) 5.0(5.0~5.0) 8.0(5.0~13.1) -17.475 <0.001
    下载: 导出CSV

    表  3  ALT正常对照组与ALT正常HCC组的AFP、AFP-L3、AFP-L3%水平比较

    Table  3.   Comparison of AFP, AFP-L3 and AFP-L3% levels between the control group with normal ALT and the HCC group with normal ALT

    项目 ALT正常对照组(n=597) ALT正常HCC组(n=598) Z P
    AFP(ng/mL) 3.4(2.4~5.7) 19.6(5.2~162.4) -18.654 <0.001
    AFP-L3(ng/mL) 0.6(0.6~0.6) 2.3(0.6~23.5) -18.512 <0.001
    AFP-L3(%) 5.0(5.0~5.0) 8.7(5.0~14.2) -17.816 <0.001
    下载: 导出CSV

    表  4  不同ALT水平的HCC组的AFP、AFP-L3、AFP-L3%水平比较

    Table  4.   Comparison of AFP, AFP-L3 and AFP-L3% levels among HCC groups with different ALT levels

    项目 ALT正常HCC组(n=598) ALT升高HCC组(n=482) Z P
    AFP(ng/mL) 19.6(5.2~162.4) 32.7(9.1~190.4) -2.961 0.003
    AFP-L3(ng/mL) 2.3(0.6~23.5) 3.2(0.6~22.8) -1.854 0.064
    AFP-L3(%) 8.7(5.0~14.2) 9.4(5.0~14.2) -1.499 0.134
    下载: 导出CSV

    表  5  AFP、AFP-L3%在总体HCC中的诊断效能分析

    Table  5.   Analysis of the diagnostic efficacy of AFP and AFP-L3% in overall HCC

    指标 AUC(95%CI 截断值 敏感度(%) 特异度(%) 约登指数 阳性预测值(%) 阴性预测值(%)
    AFP(ng/mL) 0.834(0.815~0.853) 8.5 70.4 85.0 0.554 88.8 62.9
    AFP-L3%(%) 0.766(0.748~0.785) 5.0 62.4 88.4 0.508 90.1 58.2
    AFP+AFP-L3% 0.833(0.814~0.852) NA 71.1 84.5 0.556 88.6 63.4
    注:NA,无确切截断值。
    下载: 导出CSV

    表  6  AFP、AFP-L3%在早期HCC中的诊断性能及截断值比较

    Table  6.   Diagnostic performance analysis of AFP and AFP-L3% in early stage HCC and comparison of different cut-off points

    项目 截断值 敏感度(%) 特异度(%) 阳性预测值 (%) 阴性预测值 (%) Kappa值 AUC(95%CI
    AFP(ng/mL) 8.7 66.9 85.1 81.4 72.6 0.522 0.816(0.792~0.839)
    20 48.5 94.5 89.6 65.4 0.434
    200 20.2 99.2 96.2 56.2 0.196
    400 11.6 99.5 96.0 53.7 0.113
    AFP-L3%(%) 5 58.1 88.4 82.9 68.5 0.467 0.741(0.718~0.764)
    10 40.3 93.4 85.6 61.7 0.340
    15 17.9 99.2 95.7 55.5 0.173
    AFP+AFP-L3% AFP 8.7+AFP-L3% 5 67.7 84.7 81.1 73.0 0.525 0.814(0.790~0.838)
    AFP 20+AFP-L3% 10 56.9 90.6 85.5 68.4 0.478
    AFP 20+AFP-L3% 15 51.5 94.1 89.4 66.6 0.458
    AFP 200+AFP-L3% 10 46.3 93.0 86.4 64.1 0.395
    AFP 200+AFP-L3% 15 29.4 98.6 95.3 59.0 0.282
    AFP 400+AFP-L3% 10 43.5 93.1 86.0 63.0 0.369
    AFP 400+AFP-L3% 15 24.2 98.9 95.5 57.4 0.234
    下载: 导出CSV
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