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代谢相关因素对HBV相关慢加急性肝衰竭患者短期预后的影响及预测模型构建

罗文苓 曾玉 张雪媚 盛云建

引用本文:
Citation:

代谢相关因素对HBV相关慢加急性肝衰竭患者短期预后的影响及预测模型构建

DOI: 10.12449/JCH241010
伦理学声明:本研究方案于2023年12月29日经由西南医科大学附属医院临床试验伦理委员会审批,批号:KY2023415。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:罗文苓负责课题设计,资料分析,撰写论文;曾玉、张雪媚参与收集数据,修改论文;盛云建负责拟定研究方向及写作思路,指导文章撰写、修改及定稿。
详细信息
    通信作者:

    盛云建, sheng200410@163.com (ORCID: 0000-0003-0772-5971)

Influence of metabolism-related factors on the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure and establishment of a predictive model

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    Corresponding author: SHENG Yunjian, sheng200410@163.com (ORCID: 0000-0003-0772-5971)
  • 摘要:   目的  本研究旨在评估代谢相关因素(超重和/或肥胖、高血糖、高血压及血脂紊乱)对HBV相关慢加急性肝衰竭(HBV-ACLF)患者90天预后的影响及预测模型构建。  方法  回顾性纳入2018年6月—2022年6月西南医科大学附属医院感染科收治的365例HBV-ACLF患者,根据90天随访结果分为生存组(n=273)和死亡组(n=92);收集患者的一般资料及相关实验室检查指标。符合正态分布的计量资料两组间比较采用成组t检验,非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ2检验。采用Logistic回归分析代谢相关因素是否为HBV-ACLF患者90天预后的独立危险因素,Kaplan-Meier法分析检验代谢相关因素与HBV-ALCF患者90天生存率的关系。采用受试者工作特征曲线下面积(AUC)比较不同评分模型对HBV-ACLF患者90天预后的预测价值。  结果  多因素Logistic回归分析结果显示,高血压(OR=4.698,95%CI:1.904~11.593,P=0.001)、ALT(OR=0.999,95%CI:0.999~1.000,P=0.010)、TG(OR=4.979,95%CI:2.433~10.189,P<0.001)、HDL-C(OR=0.258,95%CI:0.087~0.762,P=0.012)、载脂蛋白B(OR=0.118,95%CI:0.026~0.547,P=0.006)、CLIF-C OF评分(OR=2.275,95%CI:1.150~4.502,P<0.001)为HBV-ACLF短期预后的独立影响因素。代谢相关因素的联合预测模型AUC较单一预测模型增大,其中以高血压+TG+CLIF-C OF评分预测模型的AUC最大(AUC=0.886),合并代谢相关因素的患者肝脏相关并发症发生率更高,且30天病死率及90天病死率更高。  结论  高血压和血脂异常等代谢相关因素的存在会增加HBV-ACLF的严重程度并增加其短期死亡风险,高血压+TG+CLIF-C OF评分预测模型对HBV-ACLF患者短期预后有较好的预测价值。

     

  • 图  1  高血压/TG及联合评分预测HBV-ACLF患者90天病死率的ROC曲线

    Figure  1.  ROC curve of hypertension/TG and combined score in predicting 90 day mortality of patients with HBV-ACLF

    图  2  MS组和非MS组HBV-ACLF患者短期累积生存率分析

    Figure  2.  Analysis of short-term cumulative survival rate of HBV-ACLF patients in MS and non MS groups

    表  1  CLIF-C OF评分

    Table  1.   CLIF-C OF score

    项目 1分 2分 3分
    TBil(mg/dL) <6 6~12 >12
    Cr(mg/dL) <2 2~3.5 ≥3.5或肾脏替代
    肝性脑病分级 0 Ⅰ~Ⅱ Ⅲ~Ⅳ
    INR <2 2~2.5 ≥2.5
    平均动脉压(mmHg) ≥70 <70 应用血管活性药物
    SPO2/FiO2 >357 215~357 ≤214

    注:SPO2/FiO2,血氧饱和度/氧浓度。

    下载: 导出CSV

    表  2  生存组和死亡组基线特征的比较

    Table  2.   Comparison of baseline characteristics between the survivor group and death group

    指标 生存组(n=273) 死亡组(n=92) 统计值 P
    年龄(岁) 49.85±12.35 53.96±11.35 t=-2.279 0.023
    男/女(例) 217/56 77/15 χ2=0.778 0.378
    BMI(kg/m²) 22.83(20.77~24.98) 23.88(21.86~25.88) Z=-2.524 0.012
    合并糖尿病[例(%)] 87(31.9) 38(41.3) χ2=2.721 0.099
    合并高血压[例(%)] 21(7.7) 27(29.3) χ2=28.254 <0.001
    白细胞(×109/L) 6.41(4.90~8.42) 7.26(5.84~9.71) Z=-2.587 0.010
    中性粒细胞(×109/L) 4.38(3.21~6.19) 5.49(4.04~7.91) Z=-3.541 <0.001
    血红蛋白(g/L) 132.00(117.00~147.00) 129.00(111.00~142.75) Z=-2.115 0.034
    红细胞(×1012/L) 4.20±0.79 4.04±0.86 t=1.592 0.112
    红细胞压积(%) 0.39(0.34~0.43) 0.38(0.34~0.42) Z=-1.583 0.113
    血小板(×109/L) 110.00(74.00~153.50) 94.50(65.25~129.00) Z=-2.242 0.025
    ALT(U/L) 762.30(230.70~1 406.15) 463.35(168.98~1 047.35) Z=-2.643 0.008
    AST(U/L) 510.50(200.05~1 090.74) 359.15(186.03~954.98) Z=-1.285 0.199
    白蛋白(g/L) 33.03±4.77 30.65±4.79 t=4.133 <0.001
    总蛋白(g/L) 67.20(62.60~72.40) 66.45(61.43~70.40) Z=-1.187 0.235
    前白蛋白(g/L) 53.40(34.80~71.30) 42.55(26.45~63.85) Z=-2.697 0.007
    DBil(μmol/L) 235.40(150.35~350.50) 313.30(235.33~449.28) Z=-4.760 <0.001
    TBil(μmol/L) 173.50(102.10~254.85) 223.25(159.48~304.20) Z=-4.041 <0.001
    总胆汁酸(μmol/L) 202.21±84.72 210.44±74.89 t=-0.828 0.408
    GGT(U/L) 114.90(83.05~185.70) 104.10(72.30~170.18) Z=-1.376 0.169
    ALP(U/L) 152.00(120.25~187.35) 150.15(118.58~189.88) Z=-0.055 0.956
    Cr(μmol/L) 65.90(56.80~75.90) 67.70(54.88~87.00) Z=-1.281 0.200
    肾小球滤过率(mL/min) 107.90(94.60~119.25) 102.60(77.15~115.70) Z=-2.218 0.027
    血钾(mmol/L) 3.94±0.51 3.98±0.64 t=-0.574 0.567
    血钠(mmol/L) 139.00(136.60~141.50) 136.30(133.58~139.95) Z=-4.890 <0.001
    凝血酶原时间(s) 20.70(18.35~23.85) 25.85(21.65~32.58) Z=-6.986 <0.001
    凝血酶原时间活动度(%) 44.00(36.00~54.00) 32.50(23.00~42.00) Z=-6.745 <0.001
    INR 1.77(1.51~2.11) 2.33(1.89~3.17) Z=-7.010 <0.001
    降钙素原(ng/mL) 0.92(0.57~1.54) 1.05(0.67~2.31) Z=-1.969 0.049
    总胆固醇(mmol/L) 2.68(1.98~3.62) 2.79(2.14~3.85) Z=-1.369 0.171
    TG(mmol/L) 1.32(0.98~1.70) 1.62(1.20~2.30) Z=-3.932 <0.001
    HDL-C(mmol/L) 0.45(0.23~0.99) 0.22(0.07~0.45) Z=-5.944 <0.001
    LDL-C(mmol/L) 1.53(1.17~2.03) 1.31(1.00~1.86) Z=-2.474 0.013
    载脂蛋白B(g/L) 0.77(0.59~1.03) 0.68(0.54~0.93) Z=-2.525 0.012
    载脂蛋白A1(g/L) 0.49(0.34~0.70) 0.40(0.19~0.57) Z=-3.578 <0.001
    MELD-Na评分 23.19(20.50~26.59) 28.86(25.32~32.79) Z=-7.799 <0.001
    CLIF-C OF评分 8(7~9) 10(9~12) Z=-9.655 <0.001
    COSSH-ACLF评分 4.89(4.53~5.33) 6.05(5.35~6.93) Z=-9.309 <0.001
    下载: 导出CSV

    表  3  HBV-ACLF患者预后的Logistic回归分析

    Table  3.   Logistic regression analysis of prognosis in HBV-ACLF patients

    因素 单因素分析 多因素分析
    OR(95%CI P OR(95%CI P
    年龄 1.022(1.003~1.042) 0.024
    BMI 1.092(1.014~1.177) 0.021
    高血压 4.985(2.649~9.379) <0.001 4.698(1.904~11.593) 0.001
    白细胞 1.075(1.003~1.152) 0.041
    血红蛋白 0.987(0.976~0.998) 0.018
    血小板 0.995(0.990~1.000) 0.032
    白蛋白 0.901(0.855~0.949) 0.001
    TBil 1.004(1.002~1.006) <0.001
    ALT 0.999(0.999~1.000) 0.002 0.999(0.999~1.000) 0.010
    肾小球滤过率 0.989(0.980~0.998) 0.017
    凝血酶原时间活动度 0.939(0.920~0.958) <0.001
    INR 3.063(2.152~4.361) <0.001
    TG 2.100(1.515~2.910) <0.001 4.979(2.433~10.189) <0.001
    HDL-C 0.117(0.053~0.259) <0.001 0.258(0.087~0.762) 0.012
    LDL-C 0.646(0.445~0.938) 0.022
    载脂蛋白B 0.194(0.075~0.499) 0.001 0.118(0.026~0.547) 0.006
    载脂蛋白A1 0.326(0.145~0.735) 0.007
    MELD-Na评分 1.126(1.083~1.171) <0.001
    CLIF-C OF评分 2.226(1.849~2.680) <0.001 2.275(1.150~4.502) <0.001
    COSSH-ACLF评分 3.545(2.581~4.869) <0.001
    下载: 导出CSV

    表  4  各模型预测HBV-ACLF患者90天病死率的效能分析

    Table  4.   Efficacy analysis of various models in predicting 90 day mortality rate of HBV-ACLF patients

    评分模型 AUC 95%CI P cut-off值 敏感度 特异度
    高血压 0.608 0.537~0.680 0.002 0.5 0.293 0.923
    TG 0.637 0.569~0.705 <0.001 1.575 0.554 0.700
    MELD-Na评分 0.772 0.718~0.826 <0.001 25.027 6 0.804 0.667
    CLIF-C OF评分 0.830 0.784~0.875 <0.001 9.5 0.674 0.835
    COSSH-ACLF评分 0.824 0.777~0.872 <0.001 5.433 4 0.750 0.773
    高血压+TG+MELD-Na评分 0.831 0.785~0.877 <0.001 0.220 87 0.772 0.762
    高血压+TG+CLIF-C OF评分 0.886 0.849~0.923 <0.001 0.332 412 0.750 0.872
    高血压+TG+COSSH-ACLF评分 0.868 0.825~0.911 <0.001 0.188 104 0.837 0.758

    注:AUC,ROC曲线下面积。

    下载: 导出CSV

    表  5  HBV-ACLF患者非MS组和MS组临床资料比较

    Table  5.   Comparison of clinical data of HBV-ACLF patients between non MS group and MS group

    指标 非MS组(n=277) MS组(n=88) 统计值 P
    年龄(岁) 49.49±12.13 55.44±12.76 t=-3.419 0.001
    男[例(%)] 225(81.23) 69(78.41) χ2=0.339 0.561
    住院时间(天) 16.00(12.00~22.00) 15.00(10.25~19.00) Z=-2.071 0.038
    30天病死率[例(%)] 41(14.80) 28(31.82) χ2=12.614 <0.001
    90天病死率[例(%)] 57(20.58) 35(39.77) χ2=13.052 <0.001
    并发症[例(%)]
    细菌感染 159(57.40) 63(71.59) χ2=5.643 0.018
    肝硬化 157(56.68) 61(69.32) χ2=4.435 0.035
    腹水[例(%)] χ2=-0.721 0.471
    136(49.10) 40(45.45)
    1级 54(19.49) 17(19.32)
    2级 53(19.13) 18(20.45)
    3级 34(12.27) 13(14.77)
    肝性脑病[例(%)] χ2=-1.163 0.048
    0期 229(82.67) 69(78.41)
    1期 10(3.61) 3(3.41)
    2期 18(6.50) 2(2.27)
    3期 14(5.05) 7(7.95)
    4期 6(2.17) 7(7.95)
    白细胞(×109/L) 6.44(4.94~8.48) 7.11(5.43~9.50) Z=-1.982 0.047
    血红蛋白(g/L) 132(115~146) 132(117~144) Z=-0.176 0.861
    血小板(×109/L) 107.00(71.50~145.00) 102.00(72.25~148.50) Z=-0.249 0.804
    ALT(U/L) 692.30(204.80~1 347.75) 577.00(248.45~1 209.53) Z=-0.473 0.636
    AST(U/L) 504.20(190.25~1 054.60) 435.80(211.83~1 044.88) Z=-0.263 0.793
    白蛋白(g/L) 32.70±5.02 31.59±4.32 t=1.873 0.620
    TBil(μmol/L) 251.30(163.40~373.45) 264.25(176.90~370.25) Z=-0.510 0.610
    Cr(μmol/L) 65.80(54.75~76.55) 69.65(61.33~83.65) Z=-2.565 0.010
    肾小球滤过率(mL/min) 108.50(96.90~120.25) 98.50(81.08~113.85) Z=-3.800 <0.001
    血清钠(mmol/L) 137.60(135.20~139.75) 137.20(135.43~138.90) Z=-0.712 0.476
    凝血酶原时间(s) 21.00(18.40~25.45) 22.35(20.00~28.60) Z=-2.868 0.004
    凝血酶原活动度(%) 43.44±15.21 38.13±13.05 t=2.949 0.003
    INR 1.83(1.51~2.29) 1.97(1.70~2.64) Z=-2.849 0.004
    MELD-Na评分 24.21(21.13~28.04) 25.06(22.29~30.31) Z=-2.040 0.041
    CLIF-C OF评分 8(8~10) 9(8~10) Z=-2.141 0.032
    COSSH-ACLF评分 4.50(4.56~5.71) 5.51(4.97~6.20) Z=-4.114 <0.001
    下载: 导出CSV
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  • 收稿日期:  2024-01-02
  • 录用日期:  2024-02-22
  • 出版日期:  2024-10-25
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