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熊去氧胆酸治疗1个月后的碱性磷酸酶水平和基线红细胞分布宽度对原发性胆汁性胆管炎治疗应答的预测价值

王楠 胡蓉 卞石惠 仲威 张鹏飞 谭友文

引用本文:
Citation:

熊去氧胆酸治疗1个月后的碱性磷酸酶水平和基线红细胞分布宽度对原发性胆汁性胆管炎治疗应答的预测价值

DOI: 10.12449/JCH240310
基金项目: 

国家自然科学基金 (82000261)

中国公共卫生项目 (GWLM202002)

江苏大学医教协同创新基金重点项目 (JDY2023020)

伦理学声明:本研究方案于2023年9月30日经由江苏大学附属人民医院伦理委员会审批,批号:K-20230124-W。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王楠、张鹏飞负责课题设计,资料分析,撰写论文;卞石惠、仲威参与收集数据,修改论文;胡蓉、谭友文负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    张鹏飞, 316959714@qq.com (ORCID: 0009-0007-4358-886X)

    谭友文, tyw915@sina.com (ORCID: 0000-0002-5464-1407)

Value of alkaline phosphatase level after ursodeoxycholic acid treatment for one month and baseline red blood cell distribution width in predicting the treatment response of primary biliary cholangitis

Research funding: 

National Natural Science Foundation of China (82000261);

China Public Health Program (GWLM202002);

Key Project of Medical Education Collaborative Innovation Fund of Jiangsu University (JDY2023020)

More Information
    Corresponding author: ZHANG Pengfei, 316959714@qq.com (ORCID: 0009-0007-4358-886X); TAN Youwen, tyw915@sina.com (ORCID: 0000-0002-5464-1407)
  • 摘要:   目的  研究基线红细胞分布宽度(RDW)和熊去氧胆酸(UDCA)治疗1个月后的ALP水平预测原发性胆汁性胆管炎(PBC)患者对UDCA治疗的应答情况。  方法  回顾性分析2015年1月—2022年7月于江苏大学附属第三人民医院肝病中心确诊的127例PBC患者资料,收集基线指标、治疗1个月后以及1年后随访数据。根据巴黎-‍Ⅰ标准将患者分为应答良好组和应答欠佳组,分析2组患者临床及实验室特征,以及与UDCA应答之间的相关性,利用Logistic回归法分析与UDCA治疗应答相关的独立危险因素。利用ROC曲线下面积(AUC)确定相关指标的最佳临界值,根据界值将患者再次分组,分析两组间基线指标、应答情况的差异。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。计数资料组间比较则采用χ2检验。  结果  UDCA应答欠佳组患者基线TBil、AST/ALT、ALP、RDW、RDW-CV以及UDCA治疗1个月后的ALP水平明显高于应答良好组(Z值分别为-4.792、-3.697、-2.399、-4.102、-3.220、-4.236,P值均<0.05);应答欠佳组患者基线Alb、Hb、淋巴细胞数、红细胞比容及BMI水平明显低于应答良好组(Z值分别为-3.592、-3.603、-2.602、-3.829、-2.432,P值均<0.05);应答欠佳组患者基线前白蛋白、白球比、载脂蛋白A、游离三碘甲状腺原氨酸水平明显低于应答良好组(t值分别为4.530、3.402、3.485、3.639,P值均<0.001)。应答良好组患者存在肝硬化、合并胆囊结石胆囊炎以及贫血占比较低,两组间差异均有统计学意义(χ2值分别为20.815、3.892、12.283,P值均<0.05)。与UDCA应答相关的独立危险因素为基线RDW(OR=1.157,95%CI:1.028~1.301,P=0.015)及治疗1个月后的ALP水平(OR=1.012,95%CI:1.005~1.020,P=0.002),其AUC分别为0.713、0.720。基线RDW≥正常值上限且UDCA治疗1个月后ALP≥2.2倍正常值上限组患者UDCA应答率更低(42.6% vs 8.2%χ2=20.813,P<0.001)。  结论  基线RDW≥正常值上限同时UDCA治疗1个月后ALP≥2.2倍正常值上限的患者对UDCA的生化应答率更低。

     

  • 图  1  相关指标预测 PBC患者UDCA治疗应答欠佳的ROC曲线

    Figure  1.  ROC curve of PBC patient-related indicators predicting poor response to UDCA therapy

    表  1  PBC患者基线特征

    Table  1.   Baseline characteristics of PBC patients

    指标 数值
    性别 [例(%)]
    17(13.4)
    110(86.6)
    年龄(岁) 57±9
    BMI(kg/m2 22.3(20.7~24.2)
    TBil(μmol/L) 20.2(13.7~38.5)
    DBil(μmol/L) 9.4(5.5~23.7)
    Alb(g/L) 39.8(34.5~43.8)
    A/G 1.10±0.34
    PA(mg/L) 161.7±68.9
    ALT(U/L) 86(50~121)
    AST(U/L) 91(55~134)
    AST/ALT 1.01(0.76~1.37)
    ALP(U/L) 304(165~487)
    GGT(U/L) 301(144~534)
    a-HBDH(U/L) 147±33
    TC(mmol/L) 4.82(3.73~5.97)
    TG(mmol/L) 1.26(0.88~1.80)
    HDL(mmol/L) 1.57±0.72
    APOA(g/L) 1.38±0.48
    Hb(g/L) 121(106~130)
    Neu(×109/L) 2.57(2.02~3.45)
    Lym(×109/L) 1.29(0.95~1.64)
    PCV(% 0.36(0.32~0.39)
    RDW(fL) 46.4(43.7~49.6)
    RDW-CV(% 14.0(12.9~15.5)
    MPV(fL) 11.75±1.54
    P-LCR(% 38.9±11.4
    ANA 127(56~302)
    T3(nmol/L) 4.22±0.83
    注:A/G,白球比;PA,前白蛋白;a-HBDH,a-羟丁酸脱氢酶;APOA,载脂蛋白A;Neu,中性细胞数;Lym,淋巴细胞数;PCV,红细胞比容;RDW-CV,红细胞分布宽度变异系数;MPV,平均血小板体积;P-LCR,大型血小板比率;ANA,抗核抗体;T3,游离三碘甲状腺原氨酸。
    下载: 导出CSV

    表  2  UDCA应答良好组与UDCA应答欠佳组的临床特征比较

    Table  2.   Comparative analysis of the clinical characteristics of the good UDCA response group and the poor UDCA response group

    组别 例数 脂肪肝[例(%)] 肝硬化[例(%)] 胆囊结石胆囊炎[例(%)] 贫血[例(%)] SS-A/Ro52KD阳性[例(%)] CENP-B着丝点抗体阳性[例(%)]
    应答良好组 73 9(12.3) 27(37.0) 10(13.7) 16(21.9) 14(19.2) 16(21.9)
    应答欠佳组 54 6(11.1) 42(77.8) 15(27.8) 28(51.9) 14(25.9) 13(24.1)
    χ2 0.044 20.815 3.892 12.283 0.822 0.082
    P 0.834 P<0.001 P<0.05 P<0.001 0.364 0.775
    下载: 导出CSV

    表  3  UDCA应答良好组与UDCA应答欠佳组的实验室指标比较

    Table  3.   Comparative analysis of the laboratory test indices of the good UDCA response group and the poor UDCA response group

    指标 UDCA应答良好组(n=73) UDCA应答欠佳组(n=54) 统计值 P
    年龄(岁) 56±9 57±9 t=-0.281 0.780
    BMI(kg/m2 22.6(21.4~24.8) 21.9(20.1~23.3) Z=-2.432 0.015
    TBil(μmol/L) 15.4(11.6~22.9) 32.6(19.8~54.4) Z=-4.972 <0.001
    DBil(μmol/L) 6.8(4.6~10.4) 15.9(8.7~31.5) Z=-4.480 <0.001
    Alb(g/L) 41.2(37.7~44.3) 37.4(29.0~41.3) Z=-3.592 <0.001
    A/G 1.19±0.31 0.99±0.35 t=3.402 <0.001
    PA(mg/L) 183.9±61.6 131.8±67.3 t=4.530 <0.001
    ALT(U/L) 88(54~144) 76(42~114) Z=-1.600 0.110
    AST(U/L) 81(52~141) 103(70~125) Z=-0.744 0.457
    AST/ALT 0.92(0.71~1.23) 1.26(0.92~1.63) Z=-3.697 <0.001
    ALP(U/L) 265(162~452) 377(197~717) Z=-2.399 0.016
    GGT(U/L) 286(145~472) 410(130~566) Z=-0.744 0.457
    a-HBDH(U/L) 143±28 152±38 t=-1.435 0.154
    TC(mmol/L) 4.79(3.90~5.88) 5.07(3.56~6.61) Z=-0.268 0.789
    TG(mmol/L) 1.19(0.89~1.81) 1.29(0.88~1.68) Z=-0.263 0.792
    HDL(mmol/L) 1.68±0.69 1.44±0.75 t=1.860 0.065
    APOA(g/L) 1.50±0.43 1.21±0.49 t=3.485 <0.001
    Hb(g/L) 123(114~133) 110(94~128) Z=-3.603 <0.001
    Neu(109/L) 2.48(1.91~3.30) 2.70(2.09~3.80) Z=-1.680 0.093
    Lym(109/L) 1.36(1.02~1.87) 1.13(0.90~1.51) Z=-2.602 0.009
    PCV(%) 0.37(0.35~0.40) 0.33(0.30~0.37) Z=-3.829 <0.001
    RDW(fL) 45.0(43.0~47.9) 48.2(44.9~53.7) Z=-4.102 <0.001
    RDW-CV(%) 13.6(12.7~14.8) 14.7(13.4~16.4) Z=-3.220 <0.001
    MPV(fL) 11.56±1.45 12.01±1.63 t=-1.333 0.185
    P-LCR(%) 37.4±11.1 40.9±11.7 t=-1.702 0.091
    ANA 129(53~310) 112(58~270) Z=-0.159 0.874
    T3(nmol/L) 4.44±0.83 3.92±0.75 t=3.639 <0.001
    1月后ALP(U/L) 150(107~220) 253(164~423) Z=-4.236 <0.001
    下载: 导出CSV

    表  4  PBC患者UDCA应答欠佳的影响因素分析

    Table  4.   Analysis of factors associated with poor UDCA response in patients with PBC

    指标 OR 95%CI P
    BMI(kg/m2 0.841 0.676~1.046 0.119
    TBil(μmol/L) 1.020 0.982~1.058 0.310
    DBil(μmol/L) 0.959 0.913~1.006 0.086
    Alb(g/L) 1.004 0.860~1.172 0.964
    A/G 2.046 0.207~20.243 0.540
    PA(mg/L) 0.992 0.980~1.004 0.207
    AST/ALT 2.107 0.922~4.811 0.077
    ALP(U/L) 0.998 0.994~1.002 0.279
    APOA(g/L) 0.402 0.062~2.617 0.340
    Hb(g/L) 1.046 0.963~1.135 0.287
    Lym(109/L) 1.120 0.497~2.523 0.785
    RDW(fL) 1.157 1.028~1.301 0.015
    RDW-CV(%) 1.106 0.962~1.272 0.158
    T3(nmol/L) 0.835 0.374~1.861 0.659
    1个月后ALP(U/L) 1.012 1.005~1.020 0.002
    下载: 导出CSV

    表  5  相关指标预测UDCA治疗1年后应答欠佳的AUC值

    Table  5.   PBC patient-related indicators predict AUC for poor response after 1 year of UDCA therapy

    指标 AUC 95%CI P
    TBil 0.759 0.672~0.854 <0.001
    DBil 0.733 0.641~0.825 <0.001
    AST/ALT 0.692 0.599~0.786 <0.001
    基线ALP 0.625 0.525~0.725 0.016
    RDW 0.713 0.623~0.803 <0.001
    RDW-CV 0.667 0.572~0.763 0.001
    UDCA治疗1个月后ALP 0.720 0.631~0.810 <0.001
    下载: 导出CSV
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