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老年HBV相关慢加急性肝衰竭预后的危险因素及风险预测列线图模型构建

张仕华 柏承志 李春燕 徐理茂 徐华谦 汤善宏

引用本文:
Citation:

老年HBV相关慢加急性肝衰竭预后的危险因素及风险预测列线图模型构建

DOI: 10.12449/JCH241009
基金项目: 

四川省卫健委科研课题 (20PJ180)

伦理学声明:本研究方案于2020年7月9日由西部战区总医院伦理委员会审批,批号:2020ky005。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:张仕华、柏承志、李春燕负责研究设计,数据收集与分析,稿件撰写;张仕华、柏承志、徐理茂、徐华谦负责数据分析,稿件修改;汤善宏负责研究设计与指导,并最终定稿。
详细信息
    通信作者:

    汤善宏, tangshanhong@swjtu.edu.cn (ORCID: 0000-0001-6652-2942)

Risk factors for the prognosis of elderly patients with hepatitis B virus-related acute-on-chronic liver failure and construction of a nomogram model for risk prediction

Research funding: 

The Science Foundations of Health Commission of Sichuan Provincial (20PJ180)

More Information
  • 摘要:   目的  探讨老年HBV相关慢加急性肝衰竭(HBV-ACLF)患者的临床特点,以及影响患者近期预后的危险因素。  方法  选取2015年1月—2023年1月在西部战区总医院收治的417例HBV-ACLF患者进行回顾性研究。收集患者一般情况、血常规、生化指标、肝硬化及失代偿事件情况(腹水及分级,肝性脑病及分级)等临床资料。随访患者90天生存情况。根据年龄将患者分为老年组(≥60岁,n=106)和非老年组(<60岁,n=311),老年组中根据90天生存情况分为生存组(n=41)和死亡或移植组(n=65)。定量资料两组间比较采用成组t检验或Mann-Whitney U检验,定性资料两组间比较采用χ2检验。采用二元Logistic回归分析确定老年HBV-ACLF患者90天死亡风险的独立影响因素,构建老年HBV-ACLF患者死亡风险预测列线图模型。使用受试者工作特征曲线(ROC曲线)分别评价训练集与验证集中模型对于HBV-ACLF患者转归预测价值。绘制训练集与验证集中所构建模型的校准曲线与决策曲线,判断模型拟合程度与预测收益。  结果  老年患者的90天病死率显著高于非老年患者(P<0.05),其中老年组女性发生率、肝硬化基础发生率、肝性脑病发生率及分级、腹水发生率、肝纤维化指标水平(APRI、FIB-4)显著高于非老年组(P值均<0.05);而总胆固醇、高密度脂蛋白、白蛋白、甲胎蛋白、淋巴细胞等方面显著低于非老年组(P值均<0.05)。在老年HBV-ACLF患者中,生存组与死亡或移植组在总胆固醇、TBil、国际化标准比值(INR)、甲胎蛋白、血小板、肌酐、血清钠、单核细胞数量、肝性脑病发生率及分级等方面存在显著性差异(P值均<0.05)。此外,多因素Logistic回归分析提示INR(OR=11.351,95%CI:1.942~66.362)、单核细胞(OR=23.636,95%CI:1.388~402.529)、TBil(OR=1.007,95%CI:1.001~1.013)、血小板(OR=0.968,95%CI:0.945~0.993)为HBV-ACLF老年患者90天预后的独立影响因素(P值均<0.05),由此构建的列线图模型具有较高预测价值(ROC曲线下面积为0.915,敏感度为88.0%,特异度为86.7%),且在验证集中同样具有较高效能与拟合度,决策曲线提示获益较好,该模型与常用预测模型(MELD评分、COSSH-ACLFⅡ评分等)相比,仍具有较高预测效能。  结论  老年HBV-ACLF患者可能因肝脏合成、储备功能、再生能力下降、免疫功能紊乱等原因而表现为短期高病死率。INR、单核细胞、TBil、血小板在预测老年HBV-ACLF患者死亡风险方面具有较高价值,由此构建的列线图模型具有较高预测效能。

     

  • 图  1  老年HBV-ACLF患者90天预后的列线图模型

    Figure  1.  A 90-day prognosis model for elderly HBV-ACLF patients

    图  2  训练集与验证集模型的ROC曲线

    注: a,训练集;b,验证集。

    Figure  2.  ROC curves of training set and verification set models

    图  3  训练集与验证集模型的校准曲线

    注: a,训练集;b,验证集。

    Figure  3.  Calibration curves of training set and verification set models

    图  4  训练集与验证集模型的决策曲线

    注: a,训练集;b,验证集。

    Figure  4.  Decision curves of training set and verification set models

    图  5  列线图与其他模型评估老年HBV-ACLF预后的ROC曲线

    Figure  5.  ROC curves of the prognosis of HBV-ACLF in elderly patients with TIPM and other mode

    表  1  老年组和非老年组临床特征比较

    Table  1.   Comparison of clinical features between elderly group and non-elderly group

    指标 非老年组(n=311) 老年组(n=106) 统计值 P
    男性[例(%)] 270(81.817) 79(74.528) χ2=8.747 0.003
    90天病死率[例(%)] 100(32.154) 65(61.320) χ2=28.124 <0.001
    白细胞(×109/L) 6.175(4.592~8.198) 5.720(4.580~7.805) Z=-0.965 0.335
    血小板(×109/L) 98.766±75.747 83.248±39.374 t=2.017 0.044
    中性粒细胞(×109/L) 4.365(3.035~6.420) 4.370(3.137~5.798) Z=0.154 0.878
    淋巴细胞(×109/L) 0.980(0.740~1.412) 0.705(0.487~1.070) Z=-4.885 <0.001
    单核细胞(×109/L) 0.545(0.390~0.780) 0.540(0.360~0.780) Z=-0.699 0.485
    TBil(μmol/L) 321.370±152.156 353.437±155.964 t=-1.862 0.063
    ALT(U/L) 445.250(157.600~1 085.325) 430.900(142.675~784.125) Z=-0.751 0.453
    AST(U/L) 341.850(145.675~801.100) 388.500(182.050~953.900) Z=1.412 0.158
    白蛋白(g/L) 31.600±5.204 30.262±3.705 t=2.442 0.015
    总胆固醇(mmol/L) 2.030(1.497~2.683) 1.785(1.337~2.423) Z=-2.583 0.010
    HDL-C(mmol/L) 0.330(0.210~0.552) 0.270(0.137~0.465) Z=-2.268 0.023
    AFP(ng/mL) 76.295(19.105~217.312) 22.120(11.992~67.895) Z=-4.485 <0.001
    INR 1.780(1.570~2.170) 1.880(1.607~2.273) Z=1.065 0.287
    肌酐(μmol/L) 74.900(64.900~89.000) 78.00(63.000~104.000) Z=1.350 0.177
    血钠(mmol/L) 135.500(132.515~138.055) 134.950(131.675~138.025) Z=-1.590 0.122
    APRI 9.925(4.572~21.755) 12.435(5.362~27.358) Z=2.502 0.012
    FIB-4 8.885(5.055~16.795) 18.835(9.200~30.403) Z=7.308 <0.001
    MELD评分 22.195(19.467~25.513) 23.345(19.117~27.300) Z=1.896 0.058
    COSSH-ACLFⅡ评分 6.810(6.217~7.353) 7.725(7.192~8.588) Z=8.859 <0.001
    肝硬化基础[例(%)] 185(59.486) 87(82.075) χ2=17.787 <0.001
    上消化道出血[例(%)] 28(9.000) 7(6.604) χ2=0.592 0.442
    腹水[例(%)] 263(84.566) 99(93.396) χ2=5.384 0.020
    肝性脑病[例(%)] 62(19.936) 42(39.623) χ2=16.367 <0.001
    肝性脑病分级[例(%)] χ2=16.898 <0.001
    249(80.064) 64(60.377)
    1~2级 39(12.540) 29(27.359)
    3~4级 23(7.396) 13(12.264)
    下载: 导出CSV

    表  2  老年HBV-ACLF生存组和死亡或移植组临床特征比较

    Table  2.   Comparison of clinical features between survival group and death/transplantation group in HBV-ACLF

    指标 生存组(n=41) 死亡或移植组(n=65) 统计值 P
    男性[例(%)] 30(73.170) 49(75.385) χ2=0.065 0.799
    白细胞(×109/L) 5.320(4.230~6.860) 5.730(4.995~8.755) Z=1.606 0.108
    血小板(×109/L) 97.220±42.658 74.435±34.674 t=3.011 0.003
    中性粒细胞(×109/L) 4.250(2.995~5.480) 4.440(3.570~6.695) Z=1.284 0.199
    单核细胞(×109/L) 0.440(0.340~0.585) 0.600(0.385~0.845) Z=2.492 0.013
    TBil(μmol/L) 286.556±114.221 395.623±164.562 t=-3.714 <0.001
    ALT(U/L) 399.700(148.950~738.950) 424.700(136.900~807.000) Z=-0.204 0.838
    AST(U/L) 393.300(174.750~1 034.650) 383.300(194.250~969.800) Z=-0.139 0.889
    GGT(U/L) 119.800(76.600~174.150) 87.900(63.900~151.900) Z=-1.495 0.135
    总胆汁酸(μmol/L) 210.800(135.900~251.200) 220.800(163.700~277.900) Z=1.064 0.293
    白蛋白(g/L) 30.406±3.890 30.172±3.612 t=0.315 0.754
    前白蛋白(mg/L) 45.056±20.667 37.363±24.712 t=1.660 0.100
    总胆固醇(mmol/L) 2.223±0.817 1.740±0.742 t=3.136 0.002
    HDL-C(mmol/L) 0.372±0.205 0.308±0.207 t=1.571 0.119
    AFP(ng/mL) 55.830(12.670~115.040) 18.100(10.810~48.650) Z=-2.163 0.031
    INR 1.678±0.285 2.351±0.943 t=-4.439 <0.001
    血红蛋白(g/L) 121.000(110.500~131.000) 121.000(104.000~136.000) Z=-0.133 0.894
    肌酐(μmol/L) 79.998±29.715 101.932±62.634 t=-2.096 0.039

    续表

    下载: 导出CSV

    表  3  训练集与验证集老年HBV-ACLF患者临床特征比较

    Table  3.   Comparison of clinical features of elderly HBV-ACLF patients in training and verification

    指标 训练集(n=80) 验证集(n=26) 统计值 P
    白细胞(×109/L) 5.700(4.770~7.768) 5.795(3.735~8.428) Z=-0.389 0.697
    血小板(×109/L) 83.741±36.086 81.731±48.922 t=0.225 0.822
    中性粒细胞(×109/L) 4.395(3.510~5.730) 4.240(2.915~6.275) Z=-0.272 0.786
    单核细胞(×109/L) 0.550(0.390~0.810) 0.510(0.278~0.680) Z=-1.091 0.275
    TBil(μmol/L) 352.883±155.048 355.143±161.844 t=-0.064 0.949
    ALT(U/L) 404.600(136.425~942.525) 492.100(169.975~673.475) Z=0.073 0.941
    AST(U/L) 382.150(190.700~1 003.820) 473.200(209.325~917.600) Z=0.206 0.837
    GGT(U/L) 94.750(64.675~170.250) 104.550(67.325~168.525) Z=0.268 0.789
    总胆汁酸(μmol/L) 222.250(167.625~274.375) 200.655(146.030~280.350) Z=-0.720 0.472
    白蛋白(g/L) 30.240±3.899 30.333±3.102 t=-0.111 0.912
    前白蛋白(mg/L) 39.067±23.811 44.251±22.216 t=-0.980 0.329
    总胆固醇(mmol/L) 1.930±0.820 1.934±0.769 t=-0.045 0.964
    HDL-C(mmol/L) 0.320(0.153~0.478) 0.265(0.198~0.375) Z=-0.672 0.502
    AFP(ng/mL) 28.700(11.998~68.845) 17.295(8.303~65.988) Z=-0.977 0.329
    INR 2.147±0.927 1.918±0.330 t=1.229 0.222
    血红蛋白(g/L) 121.500(110.000~135.700) 120.500(103.500~131.500) Z=-0.551 0.582
    肌酐(μmol/L) 79.000(64.225~102.500) 78.500(61.825~108.050) Z=0.099 0.921
    血清钠(mmol/L) 134.614±5.044 133.488±4.582 t=1.011 0.315
    血清钾(mmol/L) 3.780(3.508~4.128) 3.885(3.453~4.378) Z=0.712 0.460
    血清磷(mmol/L) 0.280(0.200~0.520) 0.515(0.250~0.723) Z=1.884 0.060
    APRI 13.575(5.675~27.343) 14.325(6.045~38.193) Z=0.378 0.705
    FIB-4 18.360(9.603~31.123) 24.130(11.355~42.863) Z=1.138 0.255
    MELD评分 24.625±7.116 24.215±5.960 t=0.265 0.792
    COSSH-ACLFⅡ评分 7.927±1.073 8.102±1.093 t=-0.722 0.472
    肝性脑病[例(%)] 30(37.500) 12(46.154) χ2=0.614 0.433
    腹水[例(%)] 75(93.750) 24(92.308) χ2=0.066 0.797
    上消化道出血[例(%)] 6(7.500) 1(3.846) χ2=0.425 0.515
    肝性脑病分级[例(%)] χ2=2.124 0.346
    51(63.750) 13(50.000)
    1~2级 21(26.250) 8(30.769)
    3~4级 8(10.000) 5(19.231)
    下载: 导出CSV

    表  4  老年HBV-ACLF患者90天预后Logistic回归分析

    Table  4.   Logistic regression analysis of 90-day prognosis in elderly HBV-ACLF patients

    指标 单因素Logistic分析 多因素Logistic分析
    β OR(95%CI) P β OR(95%CI) P
    白细胞(×109/L) 0.079 1.082(0.951~1.232) 0.232
    血小板(×109/L) -0.021 0.979(0.965~0.994) 0.006 -0.032 0.968(0.945~0.993) 0.011
    中性粒细胞(×109/L) 0.081 1.084(0.942~1.248) 0.258
    淋巴细胞(×109/L) 0.066 1.068(0.483~2.363) 0.871
    单核细胞(×109/L) 1.672 5.324(1.037~27.340) 0.045 3.163 23.636(1.388~402.529) 0.029
    TBil(μmol/L) 0.008 1.008(1.003~1.013) 0.001 0.007 1.007(1.001~1.013) 0.020
    ALT(U/L) 0.001 1.000(0.999~1.001) 0.809
    AST(U/L) 0.001 1.000(0.999~1.001) 0.647
    GGT(U/L) -0.003 0.997(0.993~1.001) 0.104
    总胆汁酸(μmol/L) 0.004 1.004(0.998~1.009) 0.182
    白蛋白(g/L) 0.005 1.005(0.894~1.130) 0.931
    前白蛋白(mg/L) -0.015 0.985(0.966~1.005) 0.140
    总胆固醇(mmol/L) -1.34 0.262(0.119~0.577) 0.001
    HDL-C(mmol/L) -3.454 0.032(0.003~0.383) 0.007
    AFP(ng/mL) -0.002 0.998(0.996~1.001) 0.201
    INR 3.179 24.029(4.055~142.377) <0.001 2.429 11.351(1.942~66.362) 0.007
    血红蛋白(g/L) 0.008 1.008(0.984~1.032) 0.515
    肌酐(μmol/L) 0.013 1.013(0.998~1.029) 0.079
    血清钠(mmol/L) -0.194 0.824(0.723~0.938) 0.003
    血钾(mmol/L) 0.714 2.042(0.846~4.928) 0.112
    血磷(mmol/L) 0.853 2.346(0.488~11.268) 0.287
    肝性脑病[例(%)] 1.952 7.042(2.142~23.145) 0.001
    下载: 导出CSV
    指标 生存组(n=41) 死亡或移植组(n=65) 统计值 P
    血清钠(mmol/L) 136.588±3.510 132.919±5.197 t=3.981 <0.001
    血钾(mmol/L) 3.720(3.440~4.060) 3.890(3.550~4.215) Z=1.048 0.295
    血磷(mmol/L) 0.310(0.215~0.560) 0.300(0.195~0.700) Z=0.136 0.872
    APRI 10.205(4.855~27.389) 16.765(6.905~31.566) Z=1.268 0.205
    FIB-4 16.917(8.513~29.942) 21.098(11.827~34.941) Z=1.703 0.089
    MELD评分 20.734±4.164 26.915±7.113 t=-5.041 <0.001
    COSSH-ACLFⅡ评分 7.337±0.560 8.370±1.132 t=-5.431 <0.001
    腹水[例(%)] 36(87.805) 63(96.923) χ2=2.072 0.150
    上消化道出血[例(%)] 2(4.878) 5(7.692) χ2=0.028 0.868
    肝性脑病[例(%)] 6(14.634) 36(55.385) χ2=17.452 <0.001
    肝性脑病分级[例(%)] χ2=19.072 <0.001
    35(85.366) 29(44.615)
    1~2级 6(14.634) 23(35.385)
    3~4级 0(0.000) 13(20.000)
    下载: 导出CSV

    表  5  列线图与其他模型对老年HBV-ACLF患者预后的预测价值比较

    Table  5.   Comparison of the predictive value of TIPM and other models in elderly HBV-ACLF patients

    评分模型 AUC 截断值 敏感度 特异度 95%CI P
    列线图 0.915 0.597 0.880 0.867 0.849~0.980 <0.001
    MELD评分 0.825 25.015 0.560 0.967 0.735~0.914 <0.001
    COSSH-ACLFⅡ评分 0.853 7.725 0.680 0.900 0.771~0.935 <0.001
    TACIA评分 0.580 5.535 0.840 0.400 0.443~0.717 <0.001
    下载: 导出CSV
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