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肝纤维化-4指数(FIB-4)联合预后营养指数(PNI)对早期肝癌射频消融术后复发及生存期的预测价值

张旭 哈福双 李凤惠 高艳颖 梁静

引用本文:
Citation:

肝纤维化-4指数(FIB-4)联合预后营养指数(PNI)对早期肝癌射频消融术后复发及生存期的预测价值

DOI: 10.3969/j.issn.1001-5256.2023.11.015
基金项目: 

‍天津市医学重点学科(专科)建设项目 (TJYXZDXK-034A)

伦理学声明: 本研究方案于2019年1月经由天津市第三中心医院伦理委员会审批,批号:IRB2018-030-03。
利益冲突声明:本研究不存在任何利益冲突。
作者贡献声明:张旭负责课题设计,资料分析,撰写论文;哈福双、李凤惠、高艳颖等参与收集数据,修改论文;梁静负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    ‍梁静, haolele77@sina.com (ORCID: 0000-0001-5114-9030)

Value of fibrosis-4 combined with prognostic nutritional index in predicting recurrence and survival time after radiofrequency ablation for early-stage hepatocellular carcinoma

Research funding: 

‍Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-034A)

More Information
    Corresponding author: LIANG Jing, haolele77@sina.com (ORCID: 0000-0001-5114-9030)
  • 摘要:   目的  探讨术前肝纤维化-4指数(FIB-4)联合预后营养指数(PNI)对于早期肝癌射频治疗(RFA)术后复发的预测价值。  方法  回顾性分析2013年1月—2017年12月于天津市第三中心医院行RFA的365例初诊为早期肝癌患者的临床资料,统计患者的复发及生存情况。以术后肿瘤复发为阳性事件绘制FIB-4、PNI的ROC曲线,选取最佳cut-off值,进行FIB-4和PNI的分级,组合为FIB-4-PNI评分,据此分为FIB-4-PNI 0分组(n=207)、1分组(n=93)和2分组(n=65)。计数资料组间比较采用χ2检验。采用Kaplan-Meier生存分析及Log-rank检验分析不同FIB-4-PNI等级组无复发生存率(RFS)及总生存率(OS)的差异。采用Cox回归模型筛选影响患者RFS、OS的相关因素。  结果  所有患者的1、3和5年RFS率分别为79.2%、49.8%和34.3%,中位RFS为35个月,1、3和5年OS率分别为98.9%、86.9%和77.3%。不同FIB-4、PNI、FIB-4-PNI水平患者累积RFS率(χ2值分别为17.890、29.826、32.397,P值均<0.001)、OS率(χ2值分别为16.896、21.070、26.121,P值均<0.001)差异均有统计学意义。多因素Cox回归分析显示,糖尿病史(HR=1.418,95%CI:1.046~1.922,P=0.024),肿瘤数目2个(HR=1.516,95%CI:1.094~2.101,P=0.012)、3个(HR=2.146,95%CI:1.278~3.604,P=0.004),FIB-4-PNI 1分(HR=1.875,95%CI:1.385~2.539,P<0.001)、2分(HR=2.350,95%CI:1.706~3.236,P<0.001)是RFS的独立危险因素;肿瘤数目2个(HR=1.732,95%CI:1.005~2.983,P=0.048)、3个(HR=3.511,95%CI:1.658~7.433,P=0.001),FIB-4-PNI 1分(HR=2.094,95%CI:1.230~3.565,P=0.006)、2分(HR=3.908,95%CI:2.306~6.624,P<0.001)是影响OS的独立危险因素。  结论  FIB-4-PNI评分可作为早期肝癌RFA术后复发及总生存期的独立预测因素,可联合肿瘤特征预测患者术后的复发及生存情况。

     

  • 图  1  患者入组流程图

    Figure  1.  Flowchart retrospective selection process of patients

    图  2  FIB-4、PNI诊断患者RFS的ROC曲线

    Figure  2.  The ROC curve for recurrence of HCC diagnosed with FIB-4 and PNI

    图  3  不同FIB-4、PNI、FIB-4-PNI水平患者RFS生存曲线

    注: a,总体RFS;b,不同FIB-4分级组RFS比较;c,不同PNI分级组RFS比较;d,不同FIB-4-PNI分级组RFS比较。

    Figure  3.  Kaplan–Meier curves of RFS with different FIB-4, PNI and FIB-4-PNI grades

    图  4  不同FIB-4、PNI、FIB-4-PNI水平患者OS生存曲线

    注: a,OS;b,不同FIB-4分级OS比较;c,不同PNI分级OS比较;d,不同FIB-4-PNI分级OS比较。

    Figure  4.  Kaplan-Meier curves of OS with different FIB-4, PNI and FIB-4-PNI grades

    表  1  FIB-4和PNI联合作为预后指标分组标准

    Table  1.   Combination of FIB-4 and PNI as recurrence indices

    变量 评分(分)
    FIB-4
    ≤6.25 0
    >6.25 1
    PNI
    ≤46.20 1
    >46.20 0
    FIB-4-PNI
    FIB-4=0和PNI=0 0
    FIB-4=1和PNI=1 1
    FIB-4=2和PNI=2 2
    下载: 导出CSV

    表  2  不同FIB-4-PNI水平组临床资料比较

    Table  2.   Comparison of clinical data between different FIB-4-PNI grades

    指标 FIB-4-PNI 0分组 (n=207) FIB-4-PNI 1分组 (n=93) FIB-4-PNI 2分组 (n=65) χ2 P
    年龄[例(%)] 2.771 0.250
    <55岁 46(22.2) 29(31.2) 17(26.2)
    ≥55岁 161(77.8) 64(68.8) 48(73.8)
    性别[例(%)] 1.352 0.509
    46(22.2) 26(28.0) 14(21.5)
    161(77.8) 67(72.0) 51(78.5)
    肝硬化[例(%)] 174(84.1) 91(97.8) 60(92.3) 13.373 0.001
    肝癌家族史[例(%)] 28(13.5) 7(7.5) 11(16.9) 3.437 0.179
    糖尿病病史[例(%)] 46(22.2) 19(20.4) 11(16.9) 0.854 0.652
    肝病原因[例(%)] 6.968 0.314
    乙型肝炎 170(82.1) 76(81.7) 47(72.3)
    丙型肝炎 14(6.8) 10(10.8) 9(13.8)
    酒精肝 13(6.3) 3(3.2) 3(4.6)
    其他 10(4.8) 4(4.3) 6(9.2)
    ALT[例(%)] 6.708 0.035
    ≤45 U/L 176(85.0) 76(81.7) 46(70.8)
    >45 U/L 31(15.0) 17(18.3) 19(29.2)
    AST[例(%)] 89.514 <0.001
    ≤45 U/L 188(90.8) 78(83.9) 24(36.9)
    >45 U/L 19(9.2) 15(16.1) 41(63.1)
    Alb[例(%)] 111.260 <0.001
    ≥35 g/L 207(100.0) 72(77.4) 31(47.7)
    <35 g/L 0(0) 21(22.6) 34(52.3)
    TBil[例(%)] 48.447 <0.001
    ≤20 μmol/L 165(79.7) 64(68.8) 22(33.8)
    >20 μmol/L 42(20.3) 29(31.2) 43(66.2)
    PLT[例(%)] 100.611 <0.001
    ≥100×109/L 160(77.3) 42(45.2) 6(9.2)
    <100×109/L 47(22.7) 51(54.8) 59(90.8)
    淋巴细胞计数[例(%)] 76.494 <0.001
    ≤1.18×109/L 63(30.4) 66(71.0) 54(83.1)
    >1.18×109/L 144(69.6) 27(29.0) 11(16.9)
    AFP[例(%)] 8.285 0.016
    ≤15 ng/mL 123(59.4) 46(49.5) 26(40.0)
    >15 ng/mL 84(40.6) 47(50.5) 39(60.0)
    ALBI分级[例(%)] 229.489 <0.001
    1级 191(92.3) 31(33.3) 4(6.2)
    2级 16(7.7) 62(66.7) 54(83.1)
    3级 0(0) 0(0) 7(10.8)
    肿瘤数目[例(%)] 0.765 0.954
    1个 164(79.2) 72(77.4) 51(78.5)
    2个 32(15.5) 17(18.3) 10(15.4)
    3个 11(5.3) 4(4.3) 4(6.2)
    肿瘤直径[例(%)] 8.699 0.013
    ≤2.5 cm 102(49.3) 55(59.1) 45(69.2)
    >2.5 cm 105(50.7) 38(40.9) 20(30.8)
    BCLC分期[例(%)] 2.609 0.271
    0期 52(25.1) 26(28.0) 23(35.4)
    A期 155(74.9) 67(72.0) 42(64.6)
    下载: 导出CSV

    表  3  影响患者RFS的Cox回归模型分析

    Table  3.   Analysis of Cox proportional hazards model affecting RFS

    因素 单因素分析 多因素分析
    HR(95%CI χ2 P HR(95%CI χ2 P
    年龄(<55岁/≥55岁) 1.123(0.834~1.511) 0.580 0.446
    性别(女/男) 1.107(0.816~1.502) 0.426 0.514
    肝硬化(无/有) 1.468(0.929~2.321) 2.704 0.100
    肝病原因 1.294 0.730
    乙型肝炎 1.000
    丙型肝炎 0.790(0.499~1.252) 1.008 0.315
    酒精肝 0.981(0.547~1.758) 0.004 0.949
    其他 0.835(0.466~1.496) 0.368 0.544
    肝癌家族史(无/有) 1.128(0.777~1.637) 0.401 0.527
    糖尿病史(无/有) 1.392(1.029~1.882) 4.614 0.032 1.418(1.046~1.922) 5.068 0.024
    AFP(≤15 ng/mL/>15 ng/mL) 1.255(0.974~1.616) 3.089 0.079
    ALBI分级 22.179 <0.001
    1级 1.000
    2级 1.856(1.434~2.402) 22.105 <0.001
    3级 1.500(0.613~3.667) 0.790 0.374
    肿瘤数目 12.565 0.002 12.856 0.002
    1个 1.000 1.000
    2个 1.515(1.095~2.096) 6.291 0.012 1.516(1.094~2.101) 6.245 0.012
    3个 2.088(1.251~3.487) 7.925 0.005 2.146(1.278~3.604) 8.340 0.004
    肿瘤直径(≤2.5 cm/>2.5 cm) 1.055(0.817~1.361) 0.167 0.683
    BCLC分期(0期/A期) 1.245(0.933~1.663) 2.210 0.137
    FIB-4-PNI 30.337 <0.001 32.828 <0.001
    0分 1.000 1.000
    1分 1.764(1.306~2.384) 13.668 <0.001 1.875(1.385~2.539) 16.530 <0.001
    2分 2.308(1.678~3.176) 26.395 <0.001 2.350(1.706~3.236) 27.339 <0.001
    下载: 导出CSV

    表  4  影响患者OS的Cox回归模型分析

    Table  4.   Analysis of Cox proportional hazards model affecting OS

    因素 单因素分析 多因素分析
    HR(95%CI χ2 P HR(95%CI χ2 P
    年龄(<55岁/≥55岁) 0.688(0.432~1.096) 2.481 0.115
    性别(女/男) 0.884(0.538~1.452) 0.236 0.627
    肝硬化(无/有) 3.188(1.006~10.099) 3.883 0.049
    肝病原因 0.335 0.953
    乙型肝炎 1.000
    丙型肝炎 1.207(0.601~2.424) 0.281 0.596
    酒精肝 1.150(0.418~3.163) 0.074 0.786
    其他 1.005(0.366~2.760) 0.000 0.993
    肝癌家族史(无/有) 1.247(0.689~2.255) 0.531 0.466
    糖尿病史(无/有) 1.065(0.624~1.817) 0.053 0.817
    AFP(≤15 ng/mL/>15 ng/mL) 1.577(1.018~2.443) 4.166 0.041
    ALBI分级 18.443 <0.001
    1级 1.000
    2级 2.522(1.617~3.936) 16.609 <0.001
    3级 3.762(1.152~12.286) 4.813 0.028
    肿瘤数目 9.839 0.007 12.787 0.002
    1个 1.000 1.000
    2个 1.647(0.958~2.833) 3.258 0.071 1.732(1.005~2.983) 3.913 0.048
    3个 2.922(1.392~6.132) 8.033 0.005 3.511(1.658~7.433) 10.768 0.001
    肿瘤直径(≤2.5 cm/>2.5 cm) 1.323(0.858~2.040) 1.602 0.206
    BCLC分期(0期/A期) 1.703(0.986~2.940) 3.645 0.056
    FIB-4-PNI 23.400 <0.001 25.812 <0.001
    0分 1.000 1.000
    1分 2.060(1.211~3.504) 7.118 0.008 2.094(1.230~3.565) 7.411 0.006
    2分 3.606(2.139~6.081) 23.159 <0.001 3.908(2.306~6.624) 25.640 <0.001
    下载: 导出CSV
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