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基线HBV血清标志物联合评分对核苷(酸)类似物抗病毒治疗慢性乙型肝炎患者HBeAg血清学转换的预测价值

王扬 廖昊 邓中平 赵景 卞丹丹 任艳 蒋莹莹 刘霜 陈煜 鲁凤民 段钟平 郑素军

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Citation:

基线HBV血清标志物联合评分对核苷(酸)类似物抗病毒治疗慢性乙型肝炎患者HBeAg血清学转换的预测价值

DOI: 10.3969/j.issn.1001-5256.2023.05.011
基金项目: 

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10302201-004)

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10202203-006)

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10201201)

国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治” (2017ZX10203201-005)

伦理学声明:本研究方案于2019年5月20日经由首都医科大学附属北京佑安医院伦理委员会审批,批号:LL2018-003K。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:王扬负责整理、统计数据并撰写稿件;廖昊、邓中平给予试验平台及负责试验操作;赵景、卞丹丹、任艳、蒋莹莹负责临床数据及血清样本的收集和整理;刘霜、陈煜负责管理项目实施;鲁凤民、段钟平、郑素军负责课题设计,严格审阅及修订稿件并最后定稿。
详细信息
    通信作者:

    郑素军,zhengsujun@ccmu.edu.cn (ORCID: 0000-0002-6367-5764)

Value of combined baseline serum HBV markers in predicting HBeAg seroconversion in chronic hepatitis B patients treated by nucleos(t)ide analogues

Research funding: 

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10302201-004);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10202203-006);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10201201);

National Science and Technology Key Project on "Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment" (2017ZX10203201-005)

More Information
  • 摘要:   目的  评估基线血清指标HBV DNA、HBV RNA、HBsAg和HBcrAg联合对HBeAg阳性慢性乙型肝炎患者(CHB)核苷(酸)类似物治疗过程中HBeAg血清学转换的预测能力。  方法  以2007年6月—2008年7月首都医科大学附属北京佑安医院疑难肝病及人工肝中心组建的CHB前瞻性随访队列中83例HBeAg阳性患者为研究对象,回顾性分析基线血清HBV DNA、HBV RNA、HBsAg和HBcrAg水平。计量资料两组间比较采用成组t检验或Mann-Whitney U检验。计数资料两组间比较采用χ2检验。采用Spearman法进行相关性分析。构建Cox回归模型并计算HBeAg转换预测评分,时间依赖性受试者工作特征曲线评估病毒学标志物联合对HBeAg血清学转换的预测能力。不同组别累积转换率的计算使用Kaplan-Meier分析,差异比较采用Log-rank检验。  结果  83例HBeAg阳性患者中位随访108个月,其中44.58%(37/83)的患者发生HBeAg血清学转换。HBeAg转换组患者基线血清HBV DNA[6.23(1.99~9.28) log10IU/mL vs 7.69(2.05~8.96) log10IU/mL,Z=-2.345,P=0.019]和HBV RNA[4.81(1.40~7.53) log10拷贝/mL vs 6.22(2.00~8.49) log10拷贝/mL,Z=-1.702,P=0.010]水平显著低于未转换组;HBsAg和HBcrAg水平两组间比较,差异均无统计意义(P值均>0.05)。基于以上血清标志物构建Cox回归方程,计算联合预测HBeAg血清学转换评分中位数为0.95(范围0.37~3.45)。在总体患者中,联合评分与HBsAg、HBV DNA、HBV RNA和HBcrAg呈负相关,相关系数分别为-0.697、-0.787、-0.990和-0.819(P值均<0.001)。基于联合预测评分中位值,将患者分为高HBeAg转换组和低HBeAg转换组,预测36个月、60个月及84个月时HBeAg血清学转换率,高HBeAg转换组分别为43.90%、51.20%和63.10%,低HBeAg转换组分别为9.60%、17.00%和19.80%,两组间差异有统计学意义(χ2=11.6,P<0.001)。  结论  基于基线血清HBV标志物构建的联合预测评分可以预测CHB患者核苷(酸)类似物治疗过程中HBeAg的血清学转换。

     

  • 表  1  患者基线临床特征

    Table  1.   The baseline characteristics of patients

    指标 总数(n=83) HBeAg转换组(n=37) HBeAg未转换组(n=46) 统计值 P
    年龄(岁) 36.42±9.78 37.84±10.51 35.28±9.12 t=-1.186 0.239
    男性[例(%)] 68(81.93) 28(75.68) 40(86.96) χ2=1.762 0.184
    ETV/ADV治疗(例) 46/37 18/19 28/18 χ2=1.240 0.266
    初治/LAM经治(例) 36/47 16/21 20/26 χ2<0.001 0.983
    BMI(kg/m2) 23.89±3.71 24.24±3.18 23.61±4.10 t=-0.765 0.446
    ALT(U/L) 68.50(12.60~681.90) 69.50(14.90~681.90) 68.00(112.60~520.10) Z=-0.050 0.960
    AST(U/L) 44.00(10.90~358.80) 46.00(10.90~358.80) 41.55(12.90~249.30) Z=-0.366 0.714
    AST/ALT 0.66(0.25~2.32) 0.78(0.25~1.48) 0.74(0.26~2.32) Z=-0.788 0.431
    TBil(μmol/L) 15.00(6.70~59.40) 15.90(6.70~36.40) 14.70(7.90~59.40) Z=-0.316 0.752
    ALP(U/L) 88.15(45.00~412.20) 87.45(46.90~252.90) 88.50(45.00~412.20) Z=-0.229 0.819
    HBsAg(log10IU/mL) 3.77(-0.07~4.95) 3.48(2.15~4.74) 4.00(-0.07~4.95) Z=-1.162 0.098
    HBV DNA(log10IU/mL) 6.79(1.99~9.28) 6.23(1.99~9.28) 7.69(2.05~8.96) Z=-2.345 0.019
    HBV RNA(log10拷贝/mL) 5.45(1.40~8.49) 4.81(1.40~7.53) 6.22(2.00~8.49) Z=-1.702 0.010
    HBcrAg(log10U/mL) 7.15±1.12 6.75±1.25 7.71±0.96 t=1.981 0.054
    注:ETV,恩替卡韦;ADV,阿德福韦酯;LAM,拉米夫定。
    下载: 导出CSV

    表  2  基线病毒学标志物联合预测36、60和84个月HBeAg血清学转换的时间依赖性AUC分析

    Table  2.   The time-dependent area under the curve analysis of combined indicator for HBeAg seroconversion at month 36, 60 and 84

    时间点 AUC(95%CI) cut-off值 敏感度 特异度 阳性预测值 阴性预测值
    36个月 0.86(0.74~0.99) 1.17 0.86 0.70 0.40 0.95
    60个月 0.79(0.64~0.94) 1.09 0.82 0.71 0.52 0.91
    84个月 0.84(0.70~0.98) 0.82 0.93 0.63 0.59 0.94
    下载: 导出CSV
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  • 收稿日期:  2022-09-23
  • 录用日期:  2022-12-22
  • 出版日期:  2023-05-20
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