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富马酸丙酚替诺福韦治疗首次失代偿期乙型肝炎肝硬化患者的效果和安全性分析

荣欣欣 徐缘媛 杨广德 王霞 傅涓涓 李丽 潘修成

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富马酸丙酚替诺福韦治疗首次失代偿期乙型肝炎肝硬化患者的效果和安全性分析

DOI: 10.12449/JCH241013
基金项目: 

国家科技重大专项 (2018ZX10302206-001-003)

伦理学声明:本研究方案于2023年7月27日经由徐州医科大学附属医院伦理委员会审批,批号:XYFY2023-KL258-01。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:荣欣欣负责课题设计,资料分析,撰写论文;徐缘媛、杨广德、王霞参与收集及分析数据;傅涓涓、李丽修改论文;潘修成负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    潘修成, xzpxc68@126.com (ORCID: 0000-0001-9706-9458)

Efficacy and safety of tenofovir alafenamide fumarate in patients with first-time hepatitis B virus-related decompensated cirrhosis

Research funding: 

National Science and Technology Major Projects (2018ZX10302206-001-003)

More Information
    Corresponding author: PAN Xiucheng, xzpxc68@126.com (ORCID: 0000-0001-9706-9458)
  • 摘要:   目的  探讨富马酸丙酚替诺福韦(TAF)在首次失代偿期乙型肝炎肝硬化患者中的应用价值,明确其对肾功能和脂代谢的影响。  方法  选取2020年1月1日—2022年12月31日在徐州医科大学附属医院接受TAF抗病毒治疗的首次失代偿期乙型肝炎肝硬化住院患者57例,所有患者接受TAF抗病毒治疗。收集患者基线、治疗12、24和48周时病毒学、血清学、肝功能、肾功能、血清磷及血脂等指标。符合正态分布的计量资料组间比较采用配对t检验或单组重复测量方差分析,符合偏态分布的计量资料组间比较采用Friedman检验;计数资料采用χ2检验或Fisher确切概率法。  结果  共52例患者完成了48周随访。治疗12、24、48周后,实现HBV DNA阴转的比例分别为38.5%、63.5%、84.6%,ALT复常率分别为71.2%、82.7%、82.7%,Child-Pugh A级患者占比分别升至55.8%、73.1%、92.3%。治疗48周内,胱抑素-C(χ2=35.163, P<0.001)、血清磷水平(F=8.600,P<0.001)显著升高。血脂分析中LDL-C水平显著升高(χ2=10.064,P=0.018),TC/HDL-C比值从基线3.61(2.61~5.84)持续下降至3.27(2.70~4.36)(χ2=5.000, P=0.172)。  结论  TAF可以快速抑制失代偿期乙型肝炎肝硬化患者HBV复制和显著改善肝功能,对肾功能无明显影响,但需密切监测血脂水平。

     

  • 图  1  TAF治疗48周患者Child-Pugh评分及分级变化

    注: a,Child-Pugh评分变化;b,Child-Pugh分级占比变化。

    Figure  1.  Changes in Child-Pugh scores and status at 48 weeks of TAF treatment

    表  1  入组患者基线特征

    Table  1.   Baseline characteristics of patients

    指标 数值
    男[例(%)] 38(73.1)
    年龄(岁) 46.1±11.5
    HBeAg阳性[例(%)] 30(57.7)
    HBV DNA(log10 IU/mL) 5.82±1.18
    ALT(U/L) 109(55~415)
    TBil(μmol/L) 27.25(18.78~46.68)
    Alb(g/L) 34.34±6.73
    PT(s) 15.00(13.33~18.05)
    PLT(×109/L) 97±44
    Child-Pugh分级[例(%)]
    A级 13(25.0)
    B级 27(51.9)
    C级 12(23.1)
    Child-Pugh评分 8.37±2.23
    首次失代偿事件[例(%)]
    腹水 48(92.3)
    肝性脑病 2(3.8)
    消化道出血 2(3.8)
    SCr(μmol/L) 64(51~74)
    Cys-C(mg/L) 0.92(0.81~1.02)
    eGFR(mL·min-1·1.73m-2 108.60±18.73
    eGFR[例(%)]
    <90 mL·min-1·1.73m-2 10(19.2)
    ≥90 mL·min-1·1.73m-2 42(80.8)
    血清磷(mmol/L) 1.06±0.18
    TC(mmol/L) 3.70(3.07~4.29)
    TG(mmol/L) 1.15(0.80~1.47)
    HDL-C(mmol/L) 1.01±0.46
    LDL-C(mmol/L) 2.06(1.46~2.55)
    TC/HDL-C 3.61(2.61~5.84)
    乙型肝炎家族史[例(%)] 7(13.5)
    高血压[例(%)] 7(13.5)
    糖尿病[例(%)] 9(17.3)

    注:SCr,血肌酐;Cys-C,胱抑素-C;eGFR,估算肾小球滤过率。

    下载: 导出CSV

    表  2  TAF治疗48周患者病毒学应答和ALT变化

    Table  2.   Changes in the virological response and ALT levels at 48 weeks of TAF treatment

    指标 12周 24周 48周
    HBV DNA阴转[例(%)] 20(38.5) 33(63.5) 44(84.6)
    HBV DNA变化值(log10IU/mL) -3.83±1.24 -4.16±1.19 -4.43±1.18
    HBeAg阴转[例(%)] 6(20.0) 9(30.0) 11(36.7)
    HBeAg血清学转换[例(%)] 1(3.3) 2(6.7) 4(13.3)
    ALT复常[例(%)] 37(71.2) 43(82.7) 43(82.7)
    下载: 导出CSV

    表  3  TAF治疗48周患者肾功能和血清磷水平变化

    Table  3.   Changes in renal function and serum phosphate levels at 48 weeks of TAF treatment

    时间 SCr(μmol/L) eGFR(mL·min-1·1.73m-2 Cys-C(mg/L) 血清磷(mmol/L)
    基线 64(51~74) 108.60±18.73 0.92(0.81~1.02) 1.06±0.18
    12周 65(56~73) 108.77±19.59 0.99(0.91~1.14)1) 1.15±0.193)
    24周 65(56~82)1) 105.59±21.19 0.99(0.90~1.19)1) 1.15±0.181)
    48周 64(52~73) 108.52±18.45 1.01(0.82~1.14)2) 1.14±0.174)
    统计值 χ2=17.222 F=1.601 χ2=35.163 F=8.600
    P 0.001 0.201 <0.001 <0.001

    注:与基线比,1)P<0.001;2)P=0.003;3)P=0.001;4)P<0.001。

    下载: 导出CSV

    表  4  TAF治疗48周患者血脂变化

    Table  4.   Changes in lipid profiles levels at 48 weeks of TAF treatment

    时间 TC(mmol/L) TG(mmol/L) HDL-C(mmol/L) LDL-C(mmol/L) TC/HDL-C
    基线 3.70(3.07~4.29) 1.15(0.80~1.47) 1.01±0.46 2.06(1.46~2.55) 3.61(2.61~5.84)
    12周 3.68(3.30~4.33) 0.96(0.81~1.48) 1.13±0.36 2.22(1.71~2.61) 3.55(2.53~4.50)
    24周 3.70(3.40~4.32) 1.04(0.78~1.34) 1.22±0.351) 2.26(1.76~2.65)3) 3.21(2.70~4.16)
    48周 4.07(3.55~4.64) 1.14(0.82~1.48) 1.22±0.322) 2.39(1.96~2.94)4) 3.27(2.70~4.36)
    统计值 χ2=7.015 χ2=0.750 F=5.201 χ2=10.064 χ2=5.000
    P 0.071 0.861 0.005 0.018 0.172

    注:与基线比,1)P=0.005;2)P=0.002;3)P=0.019;4)P=0.003。

    下载: 导出CSV
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