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直接抗病毒药物治疗慢性丙型肝炎合并血小板减少患者的效果分析

王涛 李凤惠 梁静 向慧玲 刘芳 吕洪敏 钱宝鑫 田佳骏

引用本文:
Citation:

直接抗病毒药物治疗慢性丙型肝炎合并血小板减少患者的效果分析

DOI: 10.3969/j.issn.1001-5256.2022.01.014
基金项目: 

天津2019科技重大专项与工程重大疾病防治科技重大专项 (19ZXDBSY00030)

利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明:王涛负责课题设计,资料分析,撰写论文;李凤惠、向慧玲、刘芳、吕洪敏参与收集数据,修改论文;钱宝鑫、田佳骏提供统计学支持;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

Clinical effect of direct-acting antiviral agents in treatment of chronic hepatitis C patients with thrombocytopenia

Research funding: 

Tianjin Science and Technology Major Project and Critical Disease Prevention and Control Project 2019 (19ZXDBSY00030)

  • 摘要:   目的  探讨慢性丙型肝炎(CHC)合并血小板(PLT)减少患者应用直接抗病毒药物(DAA)的临床疗效及对PLT的影响。  方法  回顾分析2018年4月—2019年3月在天津市第三中心医院接受DAA治疗合并PLT减少(PLT<150×109/L)的CHC患者83例,应用无干扰素方案的DAA治疗12~24周,评估治疗结束(EOT)及结束后第12周患者病毒学应答、肝功能指标、PLT、肝硬度(LSM)的变化。正态分布的计量资料组间比较采用重复测量资料的方差分析。非正态分布的计量资料组间比较前进行正态转换,后行重复测量资料的方差分析。logistic回归分析影响PLT升高的预测因素。绘制受试者工作特征曲线(ROC曲线)评价基线LSM对治疗后PLT升高的预测价值。  结果  83例CHC合并PLT减少的患者中,肝硬化患者占61.4%,治疗结束后12周持续病毒学应答(SVR12)率为98.8%。与基线相比较,EOT及SVR12时,患者血清AST、ALT、GGT、TBil、Glo水平下降,Alb水平升高,LSM明显下降,差异均有统计学意义(P值均<0.05)。患者PLT在EOT[(110.4±44.6)×109/L]和SVR12[(109.0±47.7)×109/L]时均较基线[(97.8±33.2)×109/L]显著升高(P值均<0.01)。获得SVR12时,PLT升高与无升高组患者肝硬化比例、基线LSM及基线WBC水平差异均有统计学意义(P值均<0.05);多因素logistic回归分析表明,基线LSM是DAA治疗后PLT明显升高的独立预测因子(OR=0.929, 95%CI: 0.864~0.999, P<0.05)。基线LSM水平预测PLT升高的ROC曲线下面积为0.644,cut-off值为20.15 kPa,其灵敏度和特异度分别为81.0%和48.6%。基线PLT大于100×109/L组PLT升高幅度更明显(P<0.05)。  结论  CHC合并PLT减少患者在DAA治疗及获得SVR12后,肝功能、LSM有明显改善,基线LSM是PLT升高的独立预测因素,与基线相比较,PLT在EOT及SVR12有明显提升。

     

  • 图  1  患者纳入流程

    图  2  LSM预测DAA治疗结束后12周时PLT升高的ROC曲线

    表  1  纳入83例患者的基线临床特征

    项目 数值
    BMI(kg/m2) 23.4±3.2
    肝硬化基础[例(%)] 51(61.4)
    HCV RNA(log10IU/ml) 6.3(5.7~6.7)
    PLT(×109/L) 97.8±33.0
    WBC(×109/L) 4.4(3.9~5.4)
    Cr(μmol/L) 64.0(53.0~73.0)
    Alb(g/L) 44.4(40.5~46.8)
    ALT(U/L) 41.0(26.0~82.3)
    AST(U/L) 51.5(32.8~75.3)
    TBil(μmol/L) 17.2(13.0~25.3)
    GGT(U/L) 48.0(26.0~72.0)
    Glo(g/L) 34.4(29.7~36.8)
    LSM(kPa) 15.5(11.1~23.6)
    APRI 1.4(0.8~2.5)
    初治[例(%)] 68(81.9)
    HCV基因型[例(%)]
      1b 68(81.9)
      2a 12(14.5)
      3a 2(2.4)
      6a 1(1.2)
    下载: 导出CSV

    表  2  82例患者DAA治疗后肝功能、LSM、APPRI比较

    项目 基线 EOT SVR12
    AST(U/L) 53.0(33.0~76.5) 24.0(19.0~30.0)1) 24.0(20.0~31.0)1)
    ALT(U/L) 42.0(26.5~84.5) 18.0(14.0~26.3)1) 20.0(15.0~28.3)1)
    GGT(U/L) 47.5(25.8~73.8) 21.5(15.8~34.0)1) 21.0(15.5~30.0)1)
    Alb(g/L) 44.4(40.4~46.8) 46.8(43.8~49.3)1) 48.0(43.8~49.8)1)
    Glo(g/L) 34.1(29.7~36.8) 32.3(28.0~34.7)1) 31.4(28.3~33.5)1)
    TBil(μmol/L) 17.1(13.0~24.3) 16.8(11.6~22.4)1) 14.1(10.6~17.5)1)
    LSM(kPa) 15.2(11.0~22.8) 15.0(11.9~20.5)1) 13.1(9.9~17.4)1)2)
    APRI 1.40(0.85~2.53) 0.60(0.36~0.87)1) 0.60(0.39~1.04)1)
    注:1)与基线比较,P<0.05;2)与EOT比较,P<0.01。
    下载: 导出CSV

    表  3  PLT升高组与无升高组基线特征对比

    项目 PLT升高组(n=43) PLT无升高组(n=39) 统计值 P
    年龄(岁) 60.7±9.2 61.1±9.9 t=-0.479 0.632
    男性[例(%)] 14(32.6) 15(38.5) χ2=0.312 0.577
    肝硬化[例(%)] 21(48.8) 29(74.4) χ2=5.598 0.018
    初治[例(%)] 6(14.0) 9(23.1) χ2=1.139 0.286
    Alb(g/L) 44.7(42.2~47.4) 43.3(39.8~46.8) Z=-1.030 0.303
    Glo(g/L) 33.4(29.5~36.3) 34.8(29.6~38.1) Z=-0.730 0.465
    AST(U/L) 46(26~100) 57(35~69) Z=-0.383 0.702
    ALT(U/L) 49.5(22.8~102.3) 39.0(29.0~72.0) Z=-0.662 0.508
    ALP(U/L) 92(65~108) 86(70~99) Z=-0.430 0.667
    GGT(U/L)) 48(29~85) 42(22~72) Z=-1.109 0.267
    TBil(μmol/L) 16.9(13.1~27.0) 17.2(12.0~23.8) Z=-0.076 0.940
    AFP(ng/mL) 6.0(3.8~13.6) 6.7(3.2~14.6) Z=-0.306 0.759
    APRI 1.30(0.70~2.80) 1.41(1.04~1.91) Z=-0.482 0.630
    LSM(kPa) 13.6(10.4~19.7) 19.2(11.6~26.3) Z=-2.191 0.028
    HCV RNA(log10IU/mL) 6.4(5.7~6.8) 6.1(5.7~6.5) Z=-1.393 0.164
    WBC(×109/L) 4.8(4.1~5.8) 4.2(3.5~4.9) Z=-1.996 0.046
    PLT(×109/L) 99(79~136) 93(67~115) Z=-1.458 0.145
    HGB(g/L) 138(128~152) 136(127~149) Z=-0.683 0.495
    Cr(μmol/L) 64(52~77) 64(53~71) Z=-0.245 0.806
    下载: 导出CSV

    表  4  logistic回归分析PLT升高的预测因素

    参数 OR 95%CI P
    基线肝硬化 0.440 0.126~1.533 0.197
    基线WBC 1.225 0.809~1.853 0.337
    基线PLT 0.989 0.970~1.009 0.275
    基线LSM 0.929 0.864~0.999 0.046
    基线ALT 1.004 0.995~1.013 0.378
    基线GGT 1.012 0.997~1.028 0.122
    下载: 导出CSV
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