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肝硬化食管胃底静脉曲张破裂出血患者再出血预测模型的建立

张群 时克 王宪波

引用本文:
Citation:

肝硬化食管胃底静脉曲张破裂出血患者再出血预测模型的建立

DOI: 10.3969/j.issn.1001-5256.2022.11.011
基金项目: 

国家自然科学基金 81774234;

北京市科学技术委员会资助 Z191100006619033

伦理学声明:本研究方案于2018年4月28日经由首都医科大学附属北京地坛医院伦理委员会审批,批号:京地伦科字[2018]第(017)-01号。
利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明:张群、时克参与数据收集,分析数据;张群负责论文撰写及修改;王宪波负责课题设计,拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    王宪波,wangxianbo638@163.com

Developing the prediction model of esophagogastric variceal rebleeding in patients with liver cirrhosis based on artificial neural network

Research funding: 

National Natural Science Foundation of China 81774234;

Beijing Municipal Science & Technology Commission Z191100006619033

More Information
  • 摘要:   目的  构建可以用来预测肝硬化食管胃底静脉曲张破裂出血患者1年内再出血风险的预测模型。  方法  选取2008年8月—2017年10月于首都医科大学附属北京地坛医院住院的肝硬化食管胃底静脉曲张破裂出血患者441例,并对其进行为期1年的随访观察。以再出血作为研究终点,根据1年内是否发生再出血事件将患者分为再出血组(249例)和未再出血组(192例)。计数资料采用Fisher精确检验或者χ2检验。计量资料符合正态分布两组间比较采用t检验,不符合正态分布的两组间比较采用Mann-Whitney U检验。采用Cox单因素和多因素回归分析影响食管胃底静脉曲张破裂出血患者1年内再出血的独立影响因素,并构建预测模型,利用ROC曲线下面积评估该模型的预测性能。  结果  有249例(56.5%)患者在1年内发生食管胃底静脉曲张破裂再出血事件,Cox多因素分析显示:INR(AHR=1.566,95%CI:1.023~2.398,P=0.039)、NLR(AHR=1.033,95%CI:1.009~1.058,P=0.006)是1年内再出血的独立危险因素;而CHB(AHR=0.769,95%CI:0.597~0.991,P=0.042)、Na(AHR=0.967,95%CI:0.936~0.999,P=0.044)、内镜(AHR=0.829,95%CI:0.743~0.926,P=0.001)及手术治疗(AHR=0.246,95%CI:0.120~0.504,P<0.001)是保护因素。利用上述6个独立影响因素,成功构建了一个人工神经网络模型(https://wangxianbo.math.ink/PoRiEV-zq/index.html),其预测1年内再出血的ROC曲线下面积为0.782(95%CI:0.740~0.825),明显优于Cox回归模型的0.672(95%CI:0.622~0.722,P<0.001)、Child-Pugh评分的0.557(95%CI:0.504~0.610,P<0.001)和MELD评分的0.562(95%CI:0.509~0.616,P<0.001)。  结论  人工神经网络模型具有良好的个体化预测性能,可以作为临床食管胃底静脉曲张破裂再出血的风险评估工具。

     

  • 图  1  自变量对ANN模型构建的重要性排序

    Figure  1.  Independent variables rank the importance to ANN model construction

    图  2  ANN模型

    Figure  2.  ANN model

    图  3  ANN模型、回归模型、Child-Pugh评分和MELD评分的ROC曲线

    Figure  3.  ROC curve of ANN model, regression model, Child-Pugh scores and MELD scores

    表  1  肝硬化EVB患者基线特征

    Table  1.   Baseline characteristics of cirrhotic patients with EVB

    指标 所有患者
    (n=441)
    未再出血组
    (n=192)
    再出血组
    (n=249)
    统计值 P
    年龄(岁) 52.46±10.51 52.43±10.81 52.48±10.28 t=0.446 0.505
    男/女(例) 309/132 136/56 173/76 χ2=0.095 0.758
    病因[例(%)]
      CHB 251(56.9) 124(64.6) 127(51.0) χ2=8.152 0.004
      CHC 44(10.0) 15(7.8) 29(11.6) χ2=1.774 0.183
      ALD 122(27.7) 41(21.4) 81(32.5) χ2=6.766 0.009
      AIH 26(5.9) 14(7.3) 12(4.8) χ2=1.194 0.274
    细菌感染[例(%)] 245(55.6) 100(52.1) 145(58.2) χ2=1.660 0.198
    Child-Pugh分级[例(%)] χ2=3.948 0.047
      A/B(5~9) 377(85.5) 171(89.1) 206(82.7)
      C(10~13) 60(13.6) 19(9.9) 41(16.5)
    MELD评分 10.00(9.00~13.00) 10.00(9.00~12.00) 11.00(9.00~14.00) Z=-2.238 0.025
    ALT(U/L) 24.40(17.20~39.40) 24.35(17.23~39.93) 24.40(17.20~39.30) Z=-0.273 0.785
    AST(U/L) 30.20(21.65~49.55) 28.75(21.20~48.08) 31.50(22.15~49.75) Z=-0.676 0.499
    TBil(μmol/L) 19.50(12.75~31.25) 18.90(12.55~29.75) 20.30(12.85~33.05) Z=-1.162 0.245
    GGT(U/L) 8.50(5.50~13.85) 23.10(13.60~46.10) 29.10(15.65~69.70) Z=-2.529 0.011
    Alb(g/L) 29.97±5.78 30.17±5.76 29.82±5.80 t=0.006 0.937
    Na(mmol/L) 139.0(136.7~141.2) 139.4(137.0~141.3) 138.5(136.2~141.2) Z=-2.056 0.040
    Cr(μmol/L) 65.30(52.65~77.50) 64.25(50.93~76.78) 66.00(54.00~78.55) Z=-1.234 0.217
    GLU(mmol/L) 8.43(6.72~11.27) 8.00(6.53~10.65) 8.83(6.91~11.63) Z=-2.241 0.217
    WBC(×109/L) 4.36(2.92~6.39) 4.19(2.88~6.29) 4.50(2.92~6.50) Z=-1.001 0.317
    NLR 4.15(2.71~6.78) 3.85(2.62~6.09) 4.50(2.80~7.42) Z=-2.402 0.016
    Hb(g/L) 76.20(59.20~96.00) 76.20(58.55~97.75) 76.20(60.45~95.00) Z=-0.159 0.874
    PLT(×109/L) 60.90(43.40~79.00) 59.50(43.25~79.98) 61.00(44.05~79.00) Z=-0.055 0.956
    PT(s) 15.30(14.05~17.20) 15.00(13.93~16.80) 15.40(14.15~17.45) Z=-1.721 0.085
    INR 1.29(1.18~1.45) 1.27(1.17~1.42) 1.31(1.19~1.49) Z=-2.478 0.013
    内镜治疗次数 1.0(1.0~2.0) 2.0(1.0~2.0) 1.0(1.0~3.0) Z=-0.836 0.403
    手术治疗[例(%)] 37(8.4) 29(15.1) 8(3.2) χ2=19.944 <0.001
    TIPS[例(%)] 6(1.4) 4(2.1) 2(0.8) χ2=1.324 0.411
    β受体阻滞剂[例(%)] 24(5.4) 14(7.3) 10(4.0) χ2=0.040 0.841
    注:GLU,葡萄糖;NLR,中性粒细胞与淋巴细胞比值;PT,凝血酶原时间;INR,国际标准化比值;TIPS,经颈静脉肝内门体分流术。
    下载: 导出CSV

    表  2  肝硬化EVB患者再出血的Cox单因素和多因素分析

    Table  2.   Univariate and multivariate Cox analysis with esophagogastric variceal rebleeding

    变量 单因素分析 多因素分析
    HR(95%CI) P AHR(95%CI) P
    年龄(岁) 1.001(0.989~1.013) 0.891
    男/女 1.094(0.835~1.433) 0.514
    CHB 0.686(0.535~0.880) 0.003 0.769(0.597~0.991) 0.042
    CHC 1.330(0.903~1.960) 0.149
    ALD 1.356(1.039~1.768) 0.025
    AIH 0.732(0.410~1.308) 0.293
    细菌感染 1.248(0.970~1.606) 0.084
    ALT(U/L) 1.001(1.000~1.002) 0.040
    AST(U/L) 1.000(1.000~1.001) 0.105
    TBil(μmol/L) 1.004(1.001~1.006) 0.002
    GGT(U/L) 1.001(1.000~1.003) 0.076
    Alb(g/L) 0.989(0.968~1.011) 0.313
    Na(mmol/L) 0.950(0.919~0.982) 0.003 0.967(0.936~0.999) 0.044
    Cr(μmol/L) 1.004(1.000~1.007) 0.030
    GLU(mmol/L) 1.023(0.999~1.046) 0.056
    WBC(×109/L) 1.035(1.012~1.057) 0.002
    NLR 1.029(1.009~1.049) 0.004 1.033(1.009~1.058) 0.006
    Hb(g/L) 1.000(0.996~1.005) 0.862
    PLT(×109/L) 1.001(0.998~1.004) 0.542
    PT(s) 1.050(1.012~1.089) 0.010
    INR 1.947(1.273~2.977) 0.002 1.566(1.023~2.398) 0.039
    内镜治疗次数 0.863(0.775~0.961) 0.007 0.829(0.743~0.926) 0.001
    手术治疗 0.261(0.129~0.527) <0.001 0.246(0.120~0.504) <0.001
    TIPS 0.422(0.105~1.698) 0.225
    β受体阻滞剂 0.998(0.582~1.711) 0.994
    下载: 导出CSV
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