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熊去氧胆酸对慢性乙型肝炎患者新型冠状病毒感染的预防和治疗效果分析

崔心宇 李彦彦 朱娜 林颖莹 李鑫

引用本文:
Citation:

熊去氧胆酸对慢性乙型肝炎患者新型冠状病毒感染的预防和治疗效果分析

DOI: 10.12449/JCH240309
基金项目: 

北京市自然科学基金 (7212053)

伦理学声明:本研究于2023年2月23日经由首都医科大学附属北京地坛医院伦理委员会审批,批号:DTEC-KT2023-001-01。所纳入患者均获得知情同意。
利益冲突声明:本研究不存在任何利益冲突。
作者贡献声明:崔心宇与李彦彦为本文共同第一作者,对本文贡献等同。崔心宇、李彦彦负责课题设计,资料分析,撰写论文;李彦彦、朱娜、林颖莹参与收集样本和临床数据;李鑫、李彦彦、崔心宇负责拟定写作思路,修改论文,指导撰写文章并最后定稿。
详细信息
    通信作者:

    李鑫, leaxin@ccmu.edu.cn (ORCID: 0000-0002-2460-8753)

Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B

Research funding: 

Natural Science Foundation of Beijing (7212053)

More Information
  • 摘要:   目的  探讨慢性乙型肝炎患者服用熊去氧胆酸后对新型冠状病毒感染(COVID-19)的潜在防治效果。  方法  收集2022年1月—12月首都医科大学附属北京地坛医院324例慢性乙型肝炎患者的临床资料,根据是否服用熊去氧胆酸,分为熊去氧胆酸组和对照组。利用倾向性评分匹配法(PSM)平衡两组患者年龄、性别和慢性并发症等混杂因素,观察两组间SARS CoV-2感染率、COVID-19后症状和恢复时间的差异。对白细胞、血红蛋白、血小板、ALT、AST、Alb、ALP、TBil、甘油三酯(TG)、总胆固醇(TC)等实验室指标、疫苗接种情况和COVID-19后肝病症状的发生情况进行对比。计量资料符合正态性分布的两组间比较采用成组t检验;偏态分布两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ2检验和连续校正χ2检验。采用二元Logistic回归进行单因素分析和多因素分析,分析匹配后影响COVID-19的因素。  结果  熊去氧胆酸组87例患者,对照组237例患者,PSM后熊去氧胆酸组为78例,对照组为137例,两组间平衡性良好。熊去氧胆酸组SARS CoV-2感染率为82.1%(64/78),对照组感染率为95.6%(131/137),差异有统计学意义(χ2=10.847,P=0.001)。COVID-19后熊去氧胆酸组发生寒战(10.9% vs 38.9%,χ2=16.124,P<0.001)、咳嗽(56.3% vs 74.8%,χ2=6.889,P=0.009)的患者比例均小于对照组,差异具有统计学意义。COVID-19后熊去氧胆酸组患者恢复时间≤7天者比例达79.7%,对照组为61.1%,两组间差异具有统计学意义(χ2=6.760,P=0.009)。单因素和多因素Logistic回归分析均显示熊去氧胆酸是COVID-19的独立影响因素(OR值分别为0.21、0.17,P值均<0.05)。  结论  在慢性乙型肝炎患者中,服用熊去氧胆酸是COVID-19的保护因素,可一定程度上减轻相关症状,缩短恢复时间,在防治COVID-19方面具有重要价值。

     

  • 图  1  UDCA组和对照组恢复时间对比

    Figure  1.  Comparison of recovery time between UDCA group and control group

    表  1  UDCA组和对照组匹配前后基线特征

    Table  1.   Baseline characteristics before and after matching between UDCA group and control group

    变量 匹配前 匹配后
    UDCA组(n=87) 对照组(n=237) P UDCA组(n=78) 对照组(n=137) P
    年龄(岁) 54.6±11.4 50.3±11.3 0.003 54.0±11.7 54.0±11.5 0.895
    BMI(kg/m2 23.8±3.3 24.1±3.2 0.565 24.0±3.5 24.0±3.4 0.897
    男性[例(%)] 44(50.6) 124(52.3) 0.780 42(53.8) 72(52.6) 0.855
    吸烟[例(%)] 30(34.5) 84(35.4) 0.873 28(35.9) 48(35.0) 0.899
    饮酒[例(%)] 27(31.0) 75(31.6) 0.916 25(32.1) 44(32.1) 0.992
    慢性并发症[例(%)]
    高血压 25(28.7) 55(23.2) 0.306 21(26.9) 38(27.7) 0.898
    糖尿病 17(19.5) 42(17.7) 0.707 17(21.8) 28(20.4) 0.814
    心血管疾病 10(11.5) 18(7.6) 0.268 9(11.5) 16(11.7) 0.975
    肝硬化 39(44.8) 48(20.3) <0.001 30(38.5) 43(31.4) 0.292
    下载: 导出CSV

    表  2  匹配后UDCA组和对照组实验室指标和疫苗接种情况

    Table  2.   Laboratory indicators and vaccination status of UDCA administration group and control group after matching

    项目 UDCA组(n=78) 对照组(n=137) 统计值 P
    实验室指标
    ALT(U/L) 20.0(15.8~33.0) 23.0(16.5~36.0) Z=-1.180 0.238
    AST(U/L) 29.0(21.0~41.2) 25.0(19.0~38.0) Z=-1.532 0.126
    Alb(g/L) 40.5(33.8~45.0) 44.0(37.5~47.0) Z=-2.820 0.005
    ALP(U/L) 100.5(80.8~130.5) 75.0(58.0~108.0) Z=-4.848 <0.001
    TBil(μmol/L) 19.0(12.0~42.2) 16.0(12.0~27.5) Z=-1.796 0.072
    TC(mmol/L) 4.0±1.3 4.2±1.2 t=0.702 0.484
    TG(mmol/L) 1.1(0.8~1.6) 1.1(0.7~1.6) Z=-0.472 0.637
    WBC(×109/L) 4.9(3.6~6.3) 4.9(3.8~6.4) Z=-0.310 0.756
    Hb(g/L) 132.0(113.0~150.3) 135.0(116.5~148.0) Z=-0.445 0.567
    PLT(×109/L) 142.0(69.8~228.8) 158.0(105.0~213.5) Z=-1.215 0.224
    疫苗接种情况[例(%)] Z=-3.158 0.002
    0针 49(62.8) 56(40.9)
    1针 0(0.0) 5(3.6)
    2针 8(10.3) 11(8.0)
    3针 21(26.9) 64(46.7)
    4针 0(0.0) 1(0.7)
    下载: 导出CSV

    表  3  UDCA组与对照组COVID-19情况

    Table  3.   COVID-19 infection in UDCA group and control group

    项目 UDCA组(n=78) 对照组(n=137) χ2 P
    COVID-19[例(%)] 64(82.1) 131(95.6) 10.847 0.001
    COVID-19症状
    发热[例(%)] 62(96.9) 126(96.2) 0.059 0.807
    最高温度(℃) 38.6(38.1~39.0) 38.8(38.5~39.0) -3.081 0.078
    发热时长(d) 2.0(1.0~2.0) 2.0(1.5~3.0) -3.364 0.039
    寒战[例(%)] 7(10.9) 51(38.9) 16.124 <0.001
    咳嗽[例(%)] 36(56.3) 98(74.8) 6.889 0.009
    鼻塞[例(%)] 2(3.1) 10(7.6) 1.513 0.219
    头痛[例(%)] 11(17.2) 10(7.6) 4.084 0.043
    咽痛[例(%)] 31(48.4) 82(62.6) 3.537 0.060
    肌肉痛[例(%)] 24(37.5) 58(44.3) 0.810 0.368
    嗅觉障碍[例(%)] 19(29.7) 52(39.7) 1.860 0.173
    疲乏[例(%)] 36(56.3) 64(48.9) 0.941 0.332
    呼吸困难[例(%)] 1(1.6) 7(5.3) 1.562 0.211
    恶心[例(%)] 3(4.7) 3(2.3) 0.829 0.363
    腹泻[例(%)] 2(3.1) 1(0.8) 1.583 0.208
    下载: 导出CSV

    表  4  Logistic回归分析乙型肝炎患者COVID-19的影响因素

    Table  4.   Logistic regression analysis of hepatitis B patients infected with COVID-19

    变量 单因素分析 多因素分析
    OR(95%CI P OR(95%CI P
    UDCA 0.21(0.08~0.57) 0.002 0.17(0.06~0.49) 0.001
    年龄(≥50岁) 0.77(0.28~2.10) 0.600 0.52(0.17~1.55) 0.239
    BMI 0.96(0.85~1.10) 0.573
    男性 0.58(0.22~1.51) 0.264
    吸烟 1.02(0.39~2.67) 0.973
    饮酒 0.87(0.33~2.28) 0.770
    高血压 3.72(0.84~16.55) 0.085 4.17(0.90~19.26) 0.067
    糖尿病 5.54(0.72~42.52) 0.100
    心血管疾病 0.72(0.20~2.66) 0.623
    肝硬化 0.75(0.29~1.93) 0.550
    疫苗接种情况
    全程接种 1.60(0.19~13.44) 0.663 1.62(0.18~14.68) 0.666
    加强针 0.68(0.26~1.75) 0.421 0.42(0.14~1.21) 0.109
    注:OR,优势比;疫苗接种情况,以部分接种为参照。
    下载: 导出CSV

    表  5  UDCA组和对照组中COVID-19患者的肝病症状比较

    Table  5.   Comparison of liver disease symptoms in patients with COVID-19 in UDCA group and control group

    症状 UDCA组(n=64) 对照组(n=131) χ2 P
    肝区痛[例(%)] 2(3.1) 7(5.3) 0.481 0.488
    腹水[例(%)] 2(3.1) 4(3.1) 0.001 0.978
    水肿[例(%)] 1(1.6) 4(3.1) 0.383 0.536
    下载: 导出CSV
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  • 收稿日期:  2023-06-06
  • 录用日期:  2023-07-21
  • 出版日期:  2024-03-20
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