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失代偿期肝硬化患者再代偿的影响因素及预后分析

许丹青 李海雯 木唤 张映媛 撒采芬 刘立 杨永锐

引用本文:
Citation:

失代偿期肝硬化患者再代偿的影响因素及预后分析

DOI: 10.12449/JCH260111
基金项目: 

云南省科技计划项目 (2017FH001-088);

昆明市科技计划项目 (2025-NS-028);

昆明市卫生科研项目 (2025-03-08-002)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:许丹青负责课题设计,资料分析,撰写论文;李海雯、 张映媛、木唤、撒采芬参与收集数据,修改论文;刘立、杨永锐负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    刘立,liuli197210@163.com (ORCID: 0000-0001-7712-4931)

    杨永锐,595144613@qq.com (ORCID: 0009-0002-4707-2557)

Influencing factors for recompensation and its impact on the prognosis in patients with decompensated liver cirrhosis

Research funding: 

Science and Technology Program Fund of Yunnan Province (2017FH001-088);

Project of the Science and Technology Plan of Kunming City (2025-NS-028);

Kunming Municipal Health Science Research Project (2025-03-08-002)

More Information
  • 摘要:   目的  探讨失代偿期肝硬化患者再代偿发生的影响因素,评估再代偿发生对预后的影响,为临床早期识别中高危患者提供依据。  方法  回顾性收集2016年1月—2022年12月就诊于昆明市第三人民医院诊断为乙型肝炎、丙型肝炎、酒精性肝炎及自身免疫性肝炎相关失代偿期肝硬化患者的临床资料,将患者分为再代偿组和持续失代偿组。为控制混杂因素,以是否发生再代偿作为分组变量,以体重指数、饮酒史、人类免疫缺陷病毒感染史、甘油三酯、总胆固醇、低密度脂蛋白、高密度脂蛋白为协变量,计算倾向性评分,并采用卡钳值0.1进行1∶1最邻近匹配,经倾向性评分匹配(PSM)后,得到协变量相对均衡的再代偿组与持续失代偿组。采用单因素及多因素Cox比例风险回归模型分析再代偿影响因素,使用“rms”程序包构建列线图,绘制受试者操作特征曲线并计算曲线下面积,使用Hosmer-Lemeshow检验评估模型的拟合度,使用“Calibration Curves”程序包绘制校准曲线对模型进行评价。Kaplan-Meier法绘制生存曲线,采用Log-rank法进行组间比较。  结果  863例失代偿期肝硬化患者有305例发生再代偿,发生率为35.3%。PSM后,610例配对成功,再代偿组与持续失代偿组各305例。单因素及多因素Cox回归分析结果显示,病因[丙型肝炎(HR=0.288,P=0.002)]、男性(HR=0.701,P=0.016)、年龄(HR=0.988,P=0.047)、血红蛋白(HGB)(HR=1.006,P=0.017)、CD4 T淋巴细胞(HR=1.001,P=0.047)、经颈静脉肝内门体分流术(TIPS)(HR=1.808,P=0.024)是失代偿期肝硬化患者再代偿的独立影响因素。随访期间,116例患者发生肝病相关死亡,其中,再代偿组27例(8.85%),持续失代偿组89例(15.95%);109例患者发生肝细胞癌(HCC),其中,再代偿组23例(7.54%),持续失代偿组86例(15.41%)。Kaplan-Meier生存曲线显示,不同代偿状态患者肝病相关病死率及HCC发生率曲线明显分离,Log-rank检验提示两组患者肝病相关病死率(χ2=9.023,P=0.003)及HCC发生率(χ2=10.526,P=0.001)差异均有统计学意义。  结论  病因、性别、年龄、TIPS史、HGB、CD4 T淋巴细胞是失代偿期肝硬化患者再代偿的独立影响因素,不同病因的失代偿期肝硬化患者再代偿的发生率存在显著差异,有TIPS史、女性、低年龄、高HGB水平及高CD4 T淋巴细胞水平的失代偿期肝硬化患者更容易出现再代偿。实现再代偿是改善患者长期预后的关键,可明显降低患者长期肝病相关病死率及HCC发生率。

     

  • 注: TIPS,经颈静脉肝内门体分流术;HGB,血红蛋白;CD4+,CD4 T淋巴细胞计数。

    图  1  失代偿期肝硬化患者再代偿的列线图模型

    Figure  1.  The Nomogram for recompensation of patients with decompensated cirrhosis

    图  2  失代偿期肝硬化患者再代偿发生的ROC曲线

    Figure  2.  ROC curve of recompensation of patients with decompensated cirrhosis

    图  3  列线图模型预测失代偿期肝硬化患者再代偿的校准曲线

    Figure  3.  Calibration curve for the recompensation of patients with decompensated cirrhosis predicted by a nomogram model

    图  4  肝硬化不同代偿状态患者肝病相关病死率比较

    Figure  4.  Comparison of liver disease-related mortality among patients with different stages of liver cirrhosis compensation

    图  5  肝硬化不同代偿状态患者HCC发生率比较

    Figure  5.  Comparison of HCC incidence among patients with different degrees of liver cirrhosis compensation status

    表  1  PSM前再代偿组与持续失代偿组患者的基线资料比较

    Table  1.   Comparison of baseline data between patients with recovered compensation and those with persistent decompensated before DSM

    指标 再代偿组(n=305) 持续失代偿组(n=558) 统计值 P
    男性[例(%)] 205(67.2) 407(72.9) χ2=3.135 0.077
    2型糖尿病史[例(%)] 47(15.4) 83(14.9) χ2=0.044 0.834
    高血压病史[例(%)] 44(14.4) 69(12.4) χ2=0.736 0.391
    饮酒史[例(%)] 116(38.0) 271(48.6) χ2=8.847 0.003
    吸烟史[例(%)] 117(38.4) 244(43.7) χ2=2.334 0.127
    HIV感染史[例(%)] 8(2.6) 32(5.7) χ2=4.320 0.038
    TIPS史[例(%)] 17(5.6) 7(1.3) χ2=13.608 <0.001
    PSE史[例(%)] 33(10.8) 32(5.7) χ2=7.321 0.007
    内镜治疗史[例(%)] 48(15.7) 90(16.1) χ2=0.022 0.881
    口服NSBB[例(%)] 38(12.5) 36(6.5) χ2=9.078 0.003
    HE[例(%)] 10(3.3) 41(7.3) χ2=5.872 0.015
    感染[例(%)] 94(30.8) 221(39.6) χ2=6.568 0.010
    病因治疗[例(%)] 288(93.8) 446(79.9) χ2=29.348 <0.001
    失代偿事件[例(%)] χ2=2.999 0.083
    1种 279(91.5) 488(87.6)
    ≥2种 26(8.5) 69(12.4)
    病因[例(%)] χ2=12.592 0.006
    乙型肝炎 207(67.9) 310(55.6)
    丙型肝炎 63(20.7) 154(27.6)
    酒精性肝炎 25(8.2) 66(11.8)
    自身免疫性肝病 10(3.3) 28(5.0)
    腹水分级[例(%)] χ2=25.743 <0.001
    51(16.7) 59(10.6)
    少量 153(50.2) 236(42.3)
    中量 76(24.9) 153(27.4)
    大量 25(8.2) 110(19.7)
    Child-Pugh分级[例(%)] χ2=38.966 <0.001
    A级 75(24.6) 54(9.7)
    B级 147(48.2) 279(50.0)
    C级 83(27.2) 225(40.3)
    MELD评分[例(%)] χ2=2.128 0.345
    低危 108(35.4) 203(36.4)
    中危 64(21.0) 137(24.6)
    高危 133(43.6) 218(39.1)
    年龄(岁) 51.00(44.00~57.00) 51.00(44.75~58.25) Z=-1.346 0.178
    BMI(kg/m2 22.56(21.44~24.28) 22.77(21.69~24.51) Z=-1.362 0.173
    WBC(×109/L) 3.93(3.02~5.56) 4.06(2.86~5.68) Z=-0.101 0.919
    HGB(g/L) 127.00(107.50~142.00) 115.00(91.00~133.25) Z=-6.005 <0.001
    PLT(×109/L) 83.00(55.00~116.20) 73.00(52.00~106.25) Z=-2.502 0.012
    TBil(mmol/L) 31.80(21.45~53.55) 35.25(21.48~66.63) Z=-0.940 0.347
    AST(U/L) 58.00(37.00~109.50) 56.50(38.75~109.50) Z=-0.123 0.902
    ALT(U/L) 39.00(25.00~52.80) 37.00(25.00~65.00) Z=-1.754 0.080
    TP(g/L) 63.63±8.94 61.72±9.16 t=2.956 0.597
    Alb(g/L) 32.00(28.05~37.15) 28.50(24.70~32.90) Z=-7.964 <0.001
    TG(mmol/L) 0.82(0.60~1.15) 0.80(0.55~1.13) Z=-1.075 0.282
    CHOL(mmol/L) 3.38(2.72~3.97) 3.12(2.39~3.79) Z=-3.807 <0.001
    HDL(mmol/L) 0.95(0.61~1.25) 0.81(0.46~1.15) Z=-3.799 <0.001
    LDL(mmol/L) 1.90(1.45~2.30) 1.73(1.24~2.25) Z=-3.146 <0.001
    hs-CRP(mg/L) 3.46(1.22~10.11) 5.79(1.74~14.67) Z=-3.774 <0.001
    IL-6(pg/mL) 12.61(8.72~23.60) 18.50(10.38~34.37) Z=-4.791 <0.001
    PT (s) 16.70(15.30~18.50) 17.20(15.60~19.40) Z=-3.145 0.002
    CD4+(个/μL) 461.90(313.30~620.73) 405.05(278.37~562.80) Z=-3.419 0.001

    注:HIV,人类免疫缺陷病毒;TIPS,经颈静脉肝内门体静脉分流术;PSE,部分脾动脉栓塞术;NSBB,β受体阻滞剂;HE,肝性脑病;Child-Pugh分级,蔡尔德-皮尤分级;MELD,终末期肝病模型;BMI,体重指数;WBC,白细胞;HGB,血红蛋白;PLT,血小板;TBil,总胆红素;AST,天冬氨酸氨基转移酶;ALT,丙氨酸氨基转移酶;TP,总蛋白;Alb,白蛋白;TG,甘油三酯;CHOL,总胆固醇;HDL,高密度脂蛋白;LDL,低密度脂蛋白;hs-CRP,超敏C反应蛋白;IL-6,白细胞介素6;PT,凝血酶原时间;CD4+,CD4 T淋巴细胞计数。

    下载: 导出CSV

    表  2  PSM 后再代偿组与持续失代偿组患者的基线资料比较

    Table  2.   Comparison of baseline data between pateints with recovered compensation and those with persistent decompensation after PSM

    指标 再代偿组(n=305) 持续失代偿组(n=305) 统计值 P
    男性[例(%)] 205(67.2) 232(76.1) χ2=5.882 0.015
    2型糖尿病史[例(%)] 47(15.4) 42(13.8) χ2=0.329 0.566
    高血压病史[例(%)] 44(14.4) 25(8.2) χ2=5.899 0.015
    饮酒史[例(%)] 116(38.0) 110(36.1) χ2=0.253 0.615
    吸烟史[例(%)] 117(38.4) 100(32.8) χ2=2.067 0.151
    HIV感染史[例(%)] 8(2.6) 3(1.0) χ2=2.314 0.128
    TIPS史[例(%)] 17(5.6) 2(0.7) 0.001
    PSE史[例(%)] 33(10.8) 19(6.2) χ2=4.120 0.059
    内镜治疗史[例(%)] 48(15.7) 56(18.4) χ2=0.742 0.389
    口服NSBB[例(%)] 38(12.5) 22(7.2) χ2=4.732 0.030
    HE[例(%)] 10(3.3) 22(7.2) χ2=4.749 0.029
    感染[例(%)] 94(30.8) 135(44.3) χ2=11.753 0.001
    病因治疗[例(%)] 286(93.8) 277(90.8) χ2=1.867 0.172
    失代偿事件[例(%)] χ2=1.475 0.224
    1种 279(91.5) 270(88.5)
    ≥2种 26(8.5) 35(11.5)
    病因[例(%)] χ2=130.442 <0.001
    乙型肝炎 207(67.9) 303(99.3)
    丙型肝炎 63(20.7) 2(0.7)
    酒精性肝炎 25(8.2) 0(0.0)
    自身免疫性肝病 10(3.3) 0(0.0)
    腹水分级[例(%)] χ2=32.418 <0.001
    51(16.7) 14(4.6)
    少量 153(50.2) 158(51.8)
    中量 76(24.9) 78(25.6)
    大量 25(8.2) 55(18.0)
    Child-Pugh分级[例(%)] χ2=24.283 <0.001
    A级 75(24.6) 34(11.1)
    B级 147(48.2) 145(47.5)
    C级 83(27.2) 126(41.3)
    MELD评分[例(%)] χ2=47.261 <0.001
    低危 108(35.4) 36(11.8)
    中危 64(21.0) 83(27.2)
    高危 133(43.6) 186(61.0)
    年龄(岁) 50.71±10.04 52.70±11.27 t=-0.230 0.042
    BMI(kg/m2 22.56(21.45~24.25) 22.84(21.88~24.24) Z=-1.572 0.116
    WBC(×109/L) 3.93(3.02~5.55) 3.96(2.87~5.11) Z=-0.800 0.424
    HGB(g/L) 127.00(108.00~142.00) 117.00(96.00~134.00) Z=-4.380 <0.001
    PLT(×109/L) 83.00(55.00~116.00) 73.00(53.00~105.00) Z=-2.408 0.016
    TBil(mmol/L) 31.80(21.50~53.50) 34.00(21.00~62.70) Z=-0.331 0.741
    AST(U/L) 58.00(37.00~109.00) 54.00(38.00~100.00) Z=-0.795 0.427
    ALT(U/L) 39.00(25.00~82.00) 39.000(26.00~66.00) Z=-0.711 0.477
    TP(g/L) 63.63±8.94 61.11±8.29 t=3.615 0.364
    Alb(g/L) 32.00(28.10~37.10) 28.80(25.30~33.30) Z=-5.999 <0.001
    TG(mmol/L) 0.82(0.60~1.14) 0.72(0.52~1.01) Z=-2.831 0.005
    CHOL(mmol/L) 3.38(2.72~3.96) 3.19(2.51~3.85) Z=-2.379 0.017
    HDL(mmol/L) 0.95(0.61~1.24) 0.88(0.50~1.23) Z=-1.841 0.066
    LDL(mmol/L) 1.90(1.45~2.30) 1.76(1.32~2.25) Z=-2.395 0.017
    hs-CRP(mg/L) 3.46(1.24~10.10) 5.88(1.93~15.11) Z=-3.539 <0.001
    IL-6(pg/mL) 12.61(8.72~23.60) 16.81(8.65~30.61) Z=-2.733 0.006
    PT(s) 16.70(15.30~18.50) 17.50(15.70~19.70) Z=-3.374 0.001
    CD4+(个/μL) 461.90(313.30~620.73) 359.70(263.16~517.81) Z=-4.902 <0.001

    注:HIV,人类免疫缺陷病毒;TIPS,经颈静脉肝内门体静脉分流术;PSE,部分脾动脉栓塞术;NSBB,β受体阻滞剂;HE,肝性脑病;Child-Pugh分级,蔡尔德-皮尤分级;MELD,终末期肝病模型;BMI,体重指数;WBC,白细胞;HGB,血红蛋白;PLT,血小板;TBil,总胆红素;AST,天冬氨酸氨基转移酶;ALT,丙氨酸氨基转移酶;TP,总蛋白;Alb,白蛋白;TG,甘油三酯;CHOL,总胆固醇;HDL,高密度脂蛋白;LDL,低密度脂蛋白;hs-CRP,超敏C反应蛋白;IL-6,白细胞介素6;PT,凝血酶原时间;CD4+,CD4 T淋巴细胞计数。

    下载: 导出CSV

    表  3  PSM后肝硬化失代偿期患者再代偿影响因素的Cox单因素回归分析

    Table  3.   Univariate risk factor analysis of recompensation in decompensated liver cirrhosis patients after PSM using Cox regression

    变量 HR 95%CI P 变量 HR 95%CI P
    年龄(岁) 0.989 0.979~1.000 0.041 Child-Pugh分级
    男性 1.305 1.028~1.658 0.032 A级 1.000
    2型糖尿病史 0.921 0.675~1.257 0.604 B级 0.652 0.493~0.861 0.003
    高血压病史 0.707 0.514~0.973 0.033 C级 0.494 0.361~0.676 <0.001
    饮酒史 0.941 0.747~1.186 0.607 MELD评分
    吸烟史 0.849 0.674~1.069 0.164 低危 1.000
    HIV感染史 0.612 0.303~1.235 0.171 中危 0.480 0.352~0.655 <0.001
    TIPS史 0.480 0.294~0.784 0.003 高危 0.457 0.345~0.590 <0.001
    PSE史 0.738 0.514~1.059 0.099 BMI(kg/m2 0.981 0.936~1.028 0.420
    内镜治疗史 1.157 0.850~1.574 0.355 WBC(×109/L) 1.003 0.971~1.036 0.876
    口服NSBB 0.760 0.541~1.068 0.113 HGB(g/L) 1.008 1.004~1.012 <0.001
    HE 1.811 0.964~3.401 0.065 PLT(×109/L) 1.003 1.001~1.005 0.006
    感染 1.423 1.116~1.815 0.004 TBil(mmol/L) 1.000 0.998~1.001 0.489
    病因治疗 0.746 0.409~1.188 0.217 AST(U/L) 1.000 1.000~1.001 0.204
    失代偿事件 0.792 0.530~1.183 0.254 ALT(U/L) 1.001 1.000~1.001 0.017
    病因 TP(g/L) 1.023 1.009~1.036 0.001
    乙型肝炎 1.000 Alb(g/L) 1.043 1.027~1.061 <0.001
    丙型肝炎 3.702 2.767~4.951 <0.001 TG(mmol/L) 1.288 1.089~1.523 0.003
    酒精性肝炎 3.545 2.329~5.394 <0.001 CHOL(mmol/L) 1.114 1.025~1.210 0.011
    自身免疫性肝病 4.627 2.431~8.810 <0.001 HDL(mmol/L) 1.201 0.970~1.487 0.092
    腹水分级 LDL(mmol/L) 1.150 1.018~1.300 0.025
    1.000 hs-CRP(mg/L) 0.986 0.976~0.995 0.003
    少量 0.508 0.369~0.689 <0.001 IL-6(pg/mL) 0.995 0.992~0.999 0.012
    中量 0.507 0.355~0.724 <0.001 PT(s) 0.945 0.907~0.985 0.007
    大量 0.295 0.183~0.478 <0.001 CD4+(个/μL) 1.001 1.001~1.002 <0.001

    注:HIV,人类免疫缺陷病毒;TIPS,经颈静脉肝内门体静脉分流术;PSE,部分脾动脉栓塞术;NSBB,β受体阻滞剂;HE,肝性脑病;Child-Pugh分级,蔡尔德-皮尤分级;MELD,终末期肝病模型;BMI,体重指数;WBC,白细胞;HGB,血红蛋白;PLT,血小板;TBil,总胆红素;AST,天冬氨酸氨基转移酶;ALT,丙氨酸氨基转移酶;TP,总蛋白;Alb,白蛋白;TG,甘油三酯;CHOL,总胆固醇;HDL,高密度脂蛋白;LDL,低密度脂蛋白;hs-CRP,超敏C反应蛋白;IL-6,白细胞介素6;PT,凝血酶原时间;CD4+,CD4 T淋巴细胞计数;HR,风险比;CI,置信区间。

    下载: 导出CSV

    表  4  PSM后肝硬化失代偿期患者再代偿影响因素的Cox多因素回归分析

    Table  4.   Multivariate risk factor analysis of recompensation in decompensated liver cirrhosis patients after PSM using Cox regression

    变量 HR 95%CI P
    男性 0.701 0.524~0.937 0.016
    病因
    乙型肝炎 1.000
    丙型肝炎 0.288 0.131~0.634 0.002
    酒精性肝炎 1.139 0.539~2.407 0.733
    自身免疫性肝病 0.862 0.378~1.962 0.723
    年龄(岁) 0.988 0.976~1.000 0.047
    HGB(g/L) 1.006 1.001~1.011 0.017
    CD4+(个/μL) 1.001 1.000~1.001 0.047
    TIPS史 1.808 1.080~3.026 0.024

    注:血红蛋白;CD4+,CD4 T淋巴细胞计数;TIPS,经颈静脉肝内门体分流术;HR,风险比;CI,置信区间。

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