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高敏PCR在HBV极低病毒载量的慢性乙型肝炎患者中检测的临床意义

邱功钦 谢丹 陈姿任 欧阳石

引用本文:
Citation:

高敏PCR在HBV极低病毒载量的慢性乙型肝炎患者中检测的临床意义

DOI: 10.12449/JCH240308
基金项目: 

国家自然科学基金 (81803884)

广东高校生物靶向诊治与康复重点实验室 (2021KSYS009)

广州市医学重点学科项目(2021—2023年) 

本科生创新能力提升计划项目 (2022JXA003)

广州医科大学科研能力提升项目 (02-410-2302092XM)

2022年广州医科大学学科建设项目 (02-410-2206013)

2023年市校(院)企联合资助项目 (2023A03J0421)

2023年北京肝胆相照公益基金会资助项目 (iGandanF-1082023-RGG023)

伦理学声明:本研究方案于2023年3月28日经由广州医科大学附属第五医院伦理委员会审批,批号:GYWY-L2023-60。
利益冲突声明:本研究不存在任何利益冲突。
作者贡献声明:邱功钦负责数据收集及分析,撰写论文,修改论文;谢丹、陈姿任负责修改和校对论文;欧阳石负责研究设计,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:

    欧阳石, ouyangshi@gzhmu.edu.cn (ORCID: 0000-0003-0173-3276)

Significance of high-sensitivity polymerase chain reaction in detecting hepatitis B virus in chronic hepatitis B patients with a very low viral load

Research funding: 

National Natural Science Foundation of China (81803884);

The Key Laboratory of Guangdong Higher Education Institutes (2021KSYS009);

The Key Medical Disciplines of Guangzhou Project (2021‍ ‍—‍ ‍2023) ;

Undergraduate Innovation Ability Enhancement Program Project (2022JXA003);

Plan on Enhancing Scientific Research in GMU (02-410-2302092XM);

2022 Guangzhou Medical University Discipline Construction Projects (02-410-2206013);

2023 City School (College) Enterprise Joint Funding Projects (2023A03J0421);

The 2023 Artificial Liver Special Fund (iGandanF-1082023-RGG023)

More Information
  • 摘要:   目的  探讨使用高敏PCR在HBV极低病毒载量(HBV DNA 10~99 IU/mL)人群检测中的意义。  方法  选取2019年9月—2022年2月在广州医科大学附属第五医院接受核苷(酸)类似物(NAs)治疗≥48周且经普敏HBV DNA检测(检测下限100 IU/mL)结果为低于检测下限的慢性乙型肝炎(CHB)患者,进一步行高敏HBV DNA检测(检测下限10 IU/mL),根据结果分为极低病毒载量(VLVL,HBV DNA 10~99 IU/mL)组和完全病毒学应答(CVR,HBV DNA<10 IU/mL或未检测到)组。比较两组患者的一般特征、血清病毒学指标、生化学指标、无创肝纤维化指标,评价相关血清病毒学指标对高敏HBV DNA高于检测下限的预测价值,并探讨未实现CVR的影响因素。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。计数资料两组间比较采用χ2检验或Fisher精确检验。采用受试者工作特征曲线(ROC曲线)评价相关血清病毒学指标对高敏HBV DNA高于检测下限的预测价值。采用二元Logistic回归分析探讨未实现CVR的影响因素。  结果  共纳入106例CHB患者,其中VLVL组24例、CVR组82例。VLVL组年龄小于CVR组(P=0.004),VLVL组qHBsAg水平(P=0.002)、HBeAg阳性率(P=0.002)、pgRNA阳性率(P=0.010)及ALT水平(P=0.017)高于CVR组。qHBsAg水平预测CHB患者采用高敏HBV DNA检查结果高于检测下限(>10 IU/mL)的ROC曲线下面积为0.717(P=0.002),最佳cut-off值为1 214.5 IU/mL,敏感度为95.5%,特异度为53.9%。HBeAg阳性(OR=3.654,95%CI:1.162~11.489,P=0.027)和qHBsAg(OR=2.985,95%CI:1.058~8.422,P=0.039)是未实现CVR的独立影响因素。  结论  CHB患者经普敏检测HBV DNA低于<100 IU/mL,但经高敏PCR检测实际仍存在VLVL。VLVL患者炎症损伤水平、pgRNA阳性率以及HBeAg阳性率均显著高于CVR者。HBeAg阳性和高qHBsAg水平是CHB患者未实现CVR的独立影响因素。临床医师不应忽视CHB患者中VLVL人群,需及时行高敏HBV DNA检测。

     

  • 图  1  qHBsAg水平预测高敏HBV DNA高于检测下限的ROC曲线

    Figure  1.  ROC curve of qHBsAg titer prediction for highly sensitive HBV DNA above the lower detection limit

    表  1  VLVL组和CVR组一般资料比较

    Table  1.   Comparison of general characteristics between VLVL group and CVR group

    指标 总计(n=106) VLVL组(n=24) CVR组(n=82) 统计值 P
    年龄(岁) 33.0(27.8~42.0) 30.0(26.0~32.8) 35.0(29.0~45.0) Z=2.892 0.004
    性别[例(%)] χ2=0.167 0.683
    30(28.3) 6(25.0) 24(29.3)
    76(71.7) 18(75.0) 58(70.7)
    BMI(kg/m2 21.9(19.7~24.0) 21.9(20.2~23.9) 21.9(19.6~24.1) Z=0.183 0.855
    乙型肝炎肝硬化[例(%)] χ2=1.310 0.252
    14(13.2) 1(4.2) 13(15.9)
    92(86.8) 23(95.8) 69(84.1)
    NAs治疗时长(年) 2.7(1.7~4.4) 2.4(1.2~3.2) 2.7(1.7~4.5) Z=1.638 0.101
    下载: 导出CSV

    表  2  VLVL组和CVR组临床特征比较

    Table  2.   Comparison of clinical characteristics between VLVL group and CVR group

    指标 总计(n=106) VLVL组(n=24) CVR组(n=82) 统计值 P
    血清生化学指标
    ALT(U/L) 19.8(16.2~30.5) 30.5(18.8~43.3) 19.6(15.0~28.1) Z=2.388 0.017
    AST(U/L) 21.2(17.4~25.6) 22.2(17.4~29.9) 20.9(17.4~24.8) Z=1.018 0.309
    TBil(μmol/L) 11.3(8.5~18.0) 10.4(8.2~13.2) 11.7(8.6~18.4) Z=0.843 0.399
    AFP(ng/mL) 2.7(2.1~3.4) 2.9(2.0~3.3) 2.7(2.1~3.5) Z=0.114 0.909
    肌酐(μmol/L) 80.3±16.8 85.2±15.6 79.0±17.0 t=1.520 0.136
    总胆固醇(mmol/L) 4.2±0.8 4.2±0.6 4.2±0.9 t=0.050 0.961
    TG(mmol/L) 1.0(0.8~1.5) 1.0(0.6~1.4) 1.0(0.9~1.5) Z=0.562 0.574
    HDL(mmol/L) 1.1(1.0~1.3) 1.1(1.0~1.3) 1.0(1.0~1.3) Z=0.433 0.665
    LDL(mmol/L) 2.6±0.6 2.6±0.4 2.6±0.7 t=0.103 0.918
    无创肝纤维化指标
    LSM(kPa) 7.2(6.3~7.8) 7.1(6.6~7.8) 7.2(6.2~7.8) Z=0.460 0.646
    FIB-4评分 0.6(0.5~0.9) 0.5(0.4~0.6) 0.7(0.5~1.0) Z=3.519 <0.001
    APRI评分 0.2(0.2~0.3) 0.2(0.2~0.3) 0.2(0.2~0.3) Z=0.500 0.617
    血清病毒学指标
    qHBsAg(IU/mL) 1 397.5(611.2~4 112.8) 2 572.5(1 672.8~5 890.5) 1 123.5(378.7~3 833.0) Z=3.082 0.002
    HBeAg[例(%)] χ2=9.642 0.002
    阳性 50(47.2) 18(75.0) 32(39.0)
    阴性 56(52.8) 6(25.0) 50(61.0)
    pgRNA[例(%)]1) χ2=6.603 0.010
    阳性 28(53.8) 11(84.6) 17(43.6)
    阴性 24(46.2) 2(15.4) 22(56.4)
    注:1),pgRNA检测共52例。
    下载: 导出CSV

    表  3  二元Logistic回归分析未实现CVR的影响因素

    Table  3.   Binary Logistic regression analysis of influencing factors of incomplete virology response

    项目 β SE Wald P OR 95%CI
    HBeAg阳性 1.296 0.584 4.915 0.027 3.654 1.162~11.489
    qHBsAg(log10 IU/mL) 1.094 0.529 4.270 0.039 2.985 1.058~8.422
    常量 -5.587 1.799 9.647 0.002 0.004
    下载: 导出CSV
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