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慢性乙型肝炎免疫耐受期患者显著肝损伤的列线图模型及其预测价值分析

王春艳 杨武才 谭文辉 邓亚 郭畅 张珊 王建军 陈国凤 纪冬

王春艳, 杨武才, 谭文辉, 等. 慢性乙型肝炎免疫耐受期患者显著肝损伤的列线图模型及其预测价值分析[J]. 临床肝胆病杂志, 2021, 37(7): 1529-1533. DOI: 10.3969/j.issn.1001-5256.2021.07.010
引用本文: 王春艳, 杨武才, 谭文辉, 等. 慢性乙型肝炎免疫耐受期患者显著肝损伤的列线图模型及其预测价值分析[J]. 临床肝胆病杂志, 2021, 37(7): 1529-1533. DOI: 10.3969/j.issn.1001-5256.2021.07.010
WANG CY, YANG WC, TAN WH, et al. Value of a nomogram model in predicting significant liver injury in patients with immune-tolerant phase chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(7): 1529-1533. DOI: 10.3969/j.issn.1001-5256.2021.07.010
Citation: WANG CY, YANG WC, TAN WH, et al. Value of a nomogram model in predicting significant liver injury in patients with immune-tolerant phase chronic hepatitis B[J]. J Clin Hepatol, 2021, 37(7): 1529-1533. DOI: 10.3969/j.issn.1001-5256.2021.07.010

慢性乙型肝炎免疫耐受期患者显著肝损伤的列线图模型及其预测价值分析

DOI: 10.3969/j.issn.1001-5256.2021.07.010
基金项目: 

解放军总医院医疗大数据与人工智能研发项目 2019MBD-024

首都临床特色应用研究特色课题 Z181100001718034

菊梅肝胆病防治能力建设专项基金重点项目 2018JM12603003

详细信息
    通讯作者:

    纪冬,jidg302@126.com

  • 中图分类号: R512.62;R575.2

Value of a nomogram model in predicting significant liver injury in patients with immune-tolerant phase chronic hepatitis B

Funds: 

Medical Big Data and Artificial Intelligence Development Fund of Chinese PLA General Hospital 2019MBD-024

the Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission Z181100001718034

Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment 2018JM12603003

  • 摘要:   目的  分析慢性HBV感染免疫耐受期(IT-CHB)患者显著肝损伤的高危因素并建立列线图预测模型。  方法  回顾性分析2002年8月—2017年12月在解放军总医院第五医学中心接受肝活检的382例慢性HBV感染者的资料,按照肝组织是否存在显著肝损伤分为2组,显著肝损伤组(≥G2或S2,n=82)和非显著肝损伤组(n=300)。正态分布的计量数据2组间比较采用独立样本t检验;非正态分布数据2组间比较采用Mann- Whitney U检验; 多组比较采用Kruskal-Wallis H检验;计数资料2组间比较采用χ2检验。相关性分析采用Spearman秩相关。采用单/多因素logistic回归方法筛选高危因素,并建立列线图模型,用C-指数、ROC曲线、校准曲线以及Bootstrap法来评价列线图的区分度及校准度。  结果  2组年龄、HBV DNA载量、ALT、AST、PLT比较差异均有统计学意义(t=-7.071,Z值别为-4.924、-3.693、-6.945、-0.585、-5.723,P值均<0.001)。Logistic回归分析显示年龄(OR=1.074,95%CI: 1.043~1.107,P<0.001),HBV DNA载量(OR=0.442,95%CI: 0.314~0.624,P<0.001),AST(OR=1.096,95%CI: 1.051~1.142,P<0.001),PLT(OR=0.992,95%CI: 0.986~0.998,P=0.006)是显著肝损伤的高危因素。基于以上因素建立列线图模型,预测显著肝损伤的C-指数为0.845,并且有拟合度高的校正曲线,其ROC曲线下面积(AUC)为0.845(95%CI: 0.795~0.895),显著优于APRI(AUC=0.781,95%CI: 0.723~0.840)以及FIB-4 (AUC=0.802,95%CI: 0.746~0.859)。  结论  免疫耐受期具有显著肝损伤的患者比例并不少见,基于年龄、HBV DNA、AST、PLT构建的列线图模型具有良好的预测准确性,可用于个体化预测IT-CHB患者的显著肝损伤,减少肝活检,为抗病毒的精准治疗提供参考。

     

  • 图  1  不同年龄段与肝组织病理炎症及纤维化的关系

    图  2  HBV DNA载量与不同阶段肝组织病理炎症及纤维化的关系

    图  3  预测IT-CHB患者显著肝损伤的列线图

    表  1  患者基线的一般资料

    指标 总体(n=382) 非显著肝损伤组(n=300) 显著肝损伤组(n=82) 统计值 P
    男性[例(%)] 261(68.3) 201(67.0) 60(73.2) χ2=1.133 0.287
    年龄(岁) 33.3±10.2 31.5±9.1 39.9±11.2 t=-7.071 <0.001
    年龄段[例(%)] χ2=56.472 <0.001
      <30岁 161(42.1) 147(49.0) 14(17.1)
      30~39岁 130(34.0) 106(35.3) 24(29.3)
      40~49岁 64(16.8) 35(11.7) 29(35.4)
      ≥50岁 27(7.1) 12(4.0) 15(18.3)
    乙型肝炎家族史[例(%)] 221(57.9) 173(57.7) 48(58.5) χ2=0.020 0.888
    BMI(kg/m2) 23.2±3.53 23.0±3.4 23.7±3.9 t=-1.021 0.308
    HBV DNA(log10IU/ml) 8.4(7.8~8.8) 8.4(8.0~8.8) 7.9(6.9~8.5) Z=-4.924 <0.001
    ALT(U/L) 23.0(18.0~28.0) 23.0(18.0~28.0) 25.5(21.0~32.0) Z=-3.693 <0.001
    AST(U/L) 23.0(19.0~27.0) 21.0(19.0~26.0) 28.0(23.0~34.0) Z=-6.945 <0.001
    TBil(μmol/L) 11.1(8.3~15.3) 10.9(8.3~15.3) 11.5(8.6~15.4) Z=-0.585 0.559
    PLT(×109/L) 202(164~234) 208(176~239) 161(137~209) Z=-5.723 <0.001
    下载: 导出CSV

    表  2  显著肝损伤的logistic回归分析

    因素 单因素分析 多因素分析
    OR(95%CI) P OR(95%CI) P
    年龄 1.084 (1.057~1.113) <0.001 1.074(1.043~1.107) <0.001
    HBV DNA 0.437 (0.324~0.589) <0.001 0.442(0.314~0.624) <0.001
    ALT 1.076(1.036~1.119) <0.001 1.009(0.959~1.060) 0.736
    AST 1.132 (1.089~1.177) <0.001 1.096(1.051~1.142) <0.001
    PLT 0.985 (0.98~0.991) <0.001 0.992(0.986~0.998) 0.006
    下载: 导出CSV

    表  3  列线图、APRI、FIB-4诊断显著肝损伤的效能比较

    诊断参数 AUC 95%CI 界值 敏感度(%) 特异度(%) 阳性预测值(%) 阴性预测值(%) Youden指数
    列线图 0.845 0.795 ~ 0.895 141.4 74.4 84.7 57.0 92.4 0.59
    APRI 0.781 0.723 ~ 0.840 0.338 70.7 77.7 46.4 90.7 0.48
    FIB-4 0.802 0.746 ~ 0.859 0.882 78.1 72.3 43.5 92.3 0.50
    下载: 导出CSV
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