二维剪切波弹性成像测量脾硬度联合血小板/脾直径对乙型肝炎肝硬化患者中重度食管胃静脉曲张的评估价值

余敏睿; 杨杰; 王进勇; 周波; 姜镔; 邓宝成

doi:10.3969/j.issn.1001-5256.2021.07.019

二维剪切波弹性成像测量脾硬度联合血小板/脾直径对乙型肝炎肝硬化患者中重度食管胃静脉曲张的评估价值

DOI: 10.3969/j.issn.1001-5256.2021.07.019

余敏睿^1a,
杨杰²,
王进勇^1a,
周波^1b,
姜镔^1c, ,,
邓宝成^1a, ,

1a.
中国医科大学附属第一医院传染科，沈阳 110000
1b.
中国医科大学附属第一医院临床流行病教研室，沈阳 110000
1c.
中国医科大学附属第一医院超声科，沈阳 110000
2.
浙江大学医学院附属第四医院感染科，浙江义乌 322000

基金项目:

国家“十三五”科技重大专项 (2017ZX10103007-005)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：余敏睿负责整理分析数据，制订写作思路，撰写论文；杨杰、王进勇参与数据收集及分析；周波参与统计分析；姜镔参与数据收集，实施研究；邓宝成负责研究设计，指导撰写论文并最后定稿。

详细信息

通信作者:
姜镔，jiangbincmu@163.com

邓宝成，sydengbc@163.com

中图分类号: R575.2
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出版历程
- 收稿日期: 2020-12-09
- 录用日期: 2021-01-05
- 出版日期: 2021-07-20

Value of spleen stiffness measured by two-dimensional shear wave elastography combined with platelet count/spleen diameter ratio in evaluating moderate-to-severe gastroesophageal varices in patients with hepatitis B cirrhosis

Minrui YU^1a,
Jie YANG²,
Jinyong WANG^1a,
Bo ZHOU^1b,
Bin JIANG^{1c
, ,},
Baocheng DENG^{1a
, ,}

1a.
Department of Infectious Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110000, China
1b.
Department of Clinical Epidemiology, The First Affiliated Hospital of China Medical University, Shenyang 110000, China
1c.
Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang 110000, China
2.
Department of Infectious Diseases, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, China

Research funding:

The National Science and Technology Major Project (2017ZX10103007-005)

摘要

摘要: 目的建立乙型肝炎肝硬化患者中重度食管胃静脉曲张(GEV)的无创性诊断模型。方法选取2017年10月—2019年12月于中国医科大学附属第一医院就诊的乙型肝炎肝硬化患者。以胃镜检查结果为金标准，分为无/轻度GEV组和中重度GEV组。不符合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。采用logistic回归分析乙型肝炎肝硬化患者中重度食管胃静脉发生与二维剪切波弹性成像(2D-SWE)测量脾硬度、PLT/脾直径之间的关系，以后退法作为自变量筛选方法，建立回归方程即诊断模型并进行检验。绘制受试者工作特征曲线(ROC曲线)判断肝和脾硬度、PLT/脾直径以及诊断模型等无创性检查指标的诊断价值，得出最佳截断值，DeLong检验比较几种无创性检查指标的ROC曲线之间是否具有统计学意义。结果共纳入168例乙型肝炎肝硬化患者，其中有67例诊断为中重度GEV。肝硬化无/轻度和中重度GEV组PLT、ALT、Alb、WBC以及INR比较差异均有统计学意义(Z值分别为-6.508、-2.132、-2.470、-4.510、-5.298，P值均＜0.05)。2D-SWE测量的脾硬度、脾脏直径以及PLT/脾脏直径在两组间差异均有统计学意义(Z值分别为-7.264、-5.924、-7.028，P值均＜0.05)。PLT/脾直径ROC曲线下面积(AUC)为0.821(95%CI：0.754~0.875)，截断值为≤6.7，敏感度为83.58%，特异度为74.26%。脾硬度AUC为0.831(95%CI：0.766~0.885)，脾硬度截断值≥34.2 kPa，敏感度为85.07%，特异度为73.27%。肝硬度AUC为0.557(95%CI：0.479~0.634)，肝硬度的截断值≥10.8 kPa，特异度为79.10%，敏感度为40.59%。肝硬度与脾硬度、PLT/脾直径对GEV诊断价值的AUC比较，差异均有统计学意义(Z值分别为4.878、5.536，P值均＜0.001)。建立判断乙型肝炎肝硬化患者中重度GEV模型：Y=-0.682+0.068×脾硬度-0.225(PLT/脾直径)。诊断模型AUC为0.860(95%CI：0.799~0.909)，敏感度为79.10%，特异度为81.19%，准确度为79.1%。结论据2D-SWE测量的脾硬度联合PLT/脾直径建立的无创性诊断模型可用于辅助判断乙型肝炎肝硬化患者中重度GEV，准确度较单独使用肝硬度或脾硬度判断中重度GEV高。
- 乙型肝炎 /
- 肝硬化 /
- 食管和胃静脉曲张 /
- 弹性成像技术
Abstract: Objective To establish a noninvasive diagnostic model for moderate-to-severe gastroesophageal varices (GEV) in patients with hepatitis B cirrhosis. Methods The patients with hepatitis B cirrhosis who attended The First Affiliated Hospital of China Medical University from October 2017 to December 2019 were enrolled, and with the results of gastroscopy as the gold standard, the patients were divided into none-to-mild GEV group and moderate-to-severe GEV group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data. A logistic regression analysis was used to investigate the association of moderate-to-severe GEV with spleen stiffness measured by two-dimensional shear wave elastography (2D-SWE) and platelet count (PLT)/spleen diameter ratio in patients with hepatitis B cirrhosis, and with the backward method for independent variable screening, a regression equation, i.e., a diagnostic model, was established and validated. The receiver operating characteristic (ROC) curve was plotted to investigate the diagnostic value of noninvasive examination indices including liver and spleen stiffness, PLT/spleen diameter ratio, and the above diagnostic model and obtain their cut-off values, the DeLong test was used to compare whether there is a statistical significance between the ROC curves of the above noninvasive indices. Results A total of 168 patients with hepatitis B cirrhosis were enrolled, among whom 67 were diagnosed with moderate-to-severe GEV. There were significant differences in PLT, alanine aminotransferase, albumin, white blood cell count, and international normalized ratio between the none-to-mild GEV group and the moderate-to-severe GEV group (Z=-6.508, -2.132, -2.470, -4.510, and -5.298, all P < 0.05). There were also significant differences in spleen stiffness measured by 2D-SWE, spleen diameter, and PLT/spleen diameter ratio between the two groups (Z=-7.264, -5.924, and -7.028, all P < 0.05). The PLT/spleen diameter ratio had an area under the ROC curve (AUC) of 0.821 (95% confidence interval [CI]: 0.754-0.875) at the cut-off value of ≤6.7, with a sensitivity of 83.58% and a specificity of 74.26%; spleen stiffness had an AUC of 0.831 (95%CI: 0.766-0.885) at the cut-off value of ≥34.2 kPa, with a sensitivity of 85.07% and a specificity of 73.27%; liver stiffness had an AUC of 0.557 (95%CI: 0.479-0.634) at the cut-off value of ≥10.8 kPa, with a specificity of 79.10% and a sensitivity of 40.59%. There was a significant difference in AUC between liver stiffness and spleen stiffness, as well as between liver stiffness and PLT/spleen diameter ratio (Z=4.878 and 5.536, P < 0.001). The model of Y=-0.682+0.068×spleen stiffness-0.225 (PLT/spleen diameter ratio) was established for predicting moderate-to-severe GEV in patients with hepatitis B cirrhosis, which had an AUC of 0.860 (95%CI: 0.799-0.909), a sensitivity of 79.10%, a specificity of 81.19%, and an accuracy of 79.1%. Conclusion The noninvasive diagnostic model based on spleen stiffness measured by 2D-SWE and PLT/spleen diameter ratio can be used to assist the judgment of moderate-to-severe GEV in patients with hepatitis B cirrhosis, with a higher accuracy than liver stiffness or spleen stiffness alone.
- Hepatitis B /
- Liver Cirrhosis /
- Esophageal and Gastric Varices /
- Elasticity Imaging Techniques

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图 1 肝硬度、脾硬度及PLT/脾直径对GEV诊断价值的ROC曲线

注：a，PLT/脾直径的ROC曲线；b，脾硬度值的ROC曲线；c，肝硬度的ROC曲线；d，PLT/脾直径、脾硬度、肝硬度三者的ROC曲线。

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图 2 诊断模型预测概率的ROC曲线

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表 1 患者基本特征

项目	结果
男/女(例)	118/50
年龄(岁)	53.42(46.17~61.06)
实验室检查
WBC(×10⁹/L)	3.99(2.56~5.46)
AST(U/L)	37.43(25.33~60.50)
ALT(U/L)	30.71(20.14~58.50)
Alb(g/L)	32.40(28.16~39.00)
TBil(μmol/L)	21.65(13.00~39.95)
DBil(μmol/L)	7.90(4.66~18.55)
PLT(×10⁹/L)	87.00(60.00~134.50)
INR	1.19(1.05~1.41)
肌酐(μmol/L)	61.00(48.00~72.14)
GEV(例)
无/轻	101
中重	67
弹性成像结果
门静脉直径(cm)	1.47(1.29~1.65)
肝硬度(kPa)	15.20(9.05~20.35)
脾硬度(kPa)	34.35(22.80~40.20)
脾直径(cm)	12.86(10.79~14.94)

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表 2 无/轻度GEV与中重度GEV肝硬化患者临床特征比较

项目	无/轻度GEV(n=101)	中重度GEV(n=67)	统计值	P值
男/女(例)	72/29	46/21	χ²=0.133	0.716
年龄(岁)	53.00(44.50~61.00)	54.00(47.00~61.00)	Z=-0.905	0.365
实验室指标
WBC(×10⁹/L)	4.82(3.11~6.02)	3.19(2.02~4.04)	Z=-4.510	＜0.001
AST(U/L)	38.00(25.00~77.50)	33.00(25.00~55.00)	Z=-1.115	0.265
ALT(U/L)	37.00(21.00~81.00)	29.00(18.00~42.00)	Z=-2.132	0.033
Alb(g/L)	34.90(28.75~40.50)	30.30(27.60~35.40)	Z=-2.470	0.014
TBil(μmol/L)	19.70(11.20~45.20)	23.00(15.20~35.10)	Z=-1.095	0.274
DBil(μmol/L)	7.60(3.70~20.30)	8.70(5.70~18.20)	Z=-1.545	0.122
PLT(10⁹/L)	116.00(79.00~169.00)	64.00(51.00~83.00)	Z=-6.508	＜0.001
INR	1.07(1.00~1.29)	1.30(1.17~1.61)	Z=-5.298	＜0.001
肌酐(μmol/L)	61.00(49.00~74.00)	61.00(44.00~69.00)	Z=-0.987	0.324
门静脉主干(cm)	1.45(1.20~1.62)	1.50(1.39~1.66)	Z=-1.367	0.172
肝硬度(kPa)	14.00(8.45~20.20)	16.9(11.60~21.00)	Z=-1.261	0.207
脾硬度(kPa)	26.60(20.55~35.70)	39.90(35.70~43.30)	Z=-7.264	＜0.001
脾直径(cm)	11.60(10.00~13.94)	14.45(12.80~16.30)	Z=-5.942	＜0.001
PLT/脾直径	10.15(6.54~16.98)	4.78(2.99~6.19)	Z=-7.028	＜0.001

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表 3 肝硬度、脾硬度及PLT/脾直径对GEV诊断价值的ROC曲线比较

组别	AUC差异值	95%CI	Z值	P值
PLT/脾直径vs脾硬度	0.011	-0.066~0.088	0.274	0.784
PLT/脾直径vs肝硬度	0.263	0.157~0.369	4.878	＜0.001
脾硬度vs肝硬度	0.274	0.177~0.371	5.536	＜0.001

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表 4 乙型肝炎肝硬化患者中重度GEV的诊断模型

变量	B值	SE	Wald	P值	OR	95%CI
脾硬度	0.068	0.023	8.578	0.003	1.070	1.023~1.119
PLT/脾直径	-0.225	0.061	17.282	0.000	0.775	0.687~0.874
常量	-0.682	1.008	0.458	0.499	0.506

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表 5 诊断乙型肝炎肝硬化患者中重度GEV不同参数的正确百分比

参数	实测GEV	例数	预测GEV(例)		正确率(%)
参数	实测GEV	例数	无/轻度	中重度	正确率(%)
PLT/脾直径
	无/轻度	101	80	21	79.2
	中重度	67	17	50	74.6
脾硬度
	无/轻度	101	84	17	83.2
	中重度	67	22	45	67.2
诊断模型
	无/轻度	101	70¹⁾	21	76.9
	中重度	67	12	55	82.1
注：PLT/脾直径、脾硬度和诊断模型的总体正确率分别为77.4%、76.8%和79.1%。1)10例患者因数据缺失，未使用诊断模型。

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