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二维剪切波弹性成像和血清学模型在慢性乙型肝炎患者肝纤维化分期中的应用价值
DOI: 10.12449/JCH240312
伦理学声明：本研究方案于2022年3月1日经由福建医科大学孟超肝胆医院伦理委员会审批，批号：科审2022-028-01，所纳入患者均签署知情同意书。
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：黄玉洁负责课题设计，资料分析，撰写论文；冯斯奕指导撰写文章并最后定稿。
Application value of two-dimensional shear wave elastography and serological models in the staging of liver fibrosis in patients with chronic hepatitis B
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摘要:
目的 探讨二维剪切波弹性成像和血清学模型及其联合应用在慢性乙型肝炎患者肝纤维化分期中的诊断价值。 方法 回顾性分析2020年8月—2022年8月在福建医科大学孟超肝胆医院进行过二维剪切波弹性成像（2D-SWE）与肝组织病理学检查的327例慢性乙型肝炎患者的临床资料，提取患者的性别、年龄、血清学指标和2D-SWE结果，根据肝纤维化程度分为S0～S1组、S≥2组、S≥3组和S=4组，根据血清学指标计算血清学模型。采用Spearman相关分析法对2D-SWE和血清学模型与肝纤维化分期进行相关分析，以肝组织病理结果为标准，绘制受试者工作特征曲线，比较各参数及其联合应用诊断肝纤维化分期的效能，并采用Delong检验比较不同方法间的差异。 结果 2D-SWE检测LSM值与肝纤维化分期呈强相关性（r=0.741，P<0.001），血清学模型中除了AAR外的其他6种（APRI、FIB-4、GPR、GP、RPR、S指数）与肝纤维化分期均存在正相关（P值均<0.001）。2D-SWE诊断S≥2、S≥3和S=4肝纤维化的AUC值分别为0.878、0.932、0.942，显著高于血清学模型（P值均<0.001），其最佳截断值分别为6.9 kPa、7.9 kPa、9.4 kPa。血清学模型中APRI在诊断S≥2、S=4的AUC值最高（0.788、0.875），S指数在诊断S≥3的AUC值最高（0.846）。在诊断S≥2、S≥3、S=4时2D-SWE和APRI联合能将AUC值分别提高到0.887、0.938、0.950，诊断S≥2、S≥3、S=4时2D-SWE和S指数联合诊断的AUC值分别为0.879、0.935、0.941；但单独使用2D-SWE与上述联合诊断并无统计学差异（P值均>0.05）。 结论 2D-SWE对肝纤维化分期的诊断效能显著优于7种血清学模型；血清学模型具有一定的诊断价值，其中APRI、S指数的价值较高；单独使用2D-SWE与指标联合并无明显差异，联合并不能显著提高诊断效能，新的联合诊断方法仍有待探索。 Abstract:Objective To investigate the value of two-dimensional shear wave elastography （2D-SWE） or serological models used alone or in combination in determining the stage of liver fibrosis in patients with chronic hepatitis B. Methods A retrospective analysis was performed for the clinical data of 327 patients with chronic hepatitis B who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from August 2020 to August 2022 and underwent 2D-SWE and liver histopathological examination， including sex， age， serological markers， and 2D-SWE results. According to the degree of liver fibrosis， they were divided into S0-S1， S≥2， S≥3， and S=4 groups， and the serological models were calculated based on serological markers. A Spearman correlation analysis was used to investigate the correlation of 2D-SWE and serological models with liver fibrosis stage； the receiver operating characteristic curve was plotted with the results of liver histopathology as the standard to compare the efficiency of each parameter used alone or in combination in determining the stage of liver fibrosis； the Delong test was used to investigate the difference between different methods. Results Liver stiffness measurement measured by 2D-SWE was strongly correlated with the stage of liver fibrosis （r=0.741， P<0.001）， and as for the serological model， six markers （APRI， FIB-4， GPR， GP， RPR， and S index）， other than AAR， were positively correlated with the stage of liver fibrosis （all P<0.001）. 2D-SWE had an area under the ROC curve （AUC） of 0.878， 0.932， and 0.942， respectively， in the diagnosis of S≥2， S≥3， and S=4 liver fibrosis （all P<0.001）， with an optimal cut-off value of 6.9 kPa， 7.9 kPa， and 9.4 kPa， respectively. Among the serological models， APRI had the largest AUC of 0.788 and 0.875， respectively， in the diagnosis of S≥2 and S=4 liver fibrosis， and S index had the largest AUC of 0.846 in the diagnosis of S≥3 liver fibrosis. In the diagnosis of S≥2， S≥3， and S=4 liver fibrosis， 2D-SWE combined with APRI increased the AUC values to 0.887， 0.938， and 0.950， respectively， and 2D-SWE combined with S index increased the AUC values to 0.879， 0.935， and 0.941， respectively， while there were no significant differences between 2D-SWE and the above combinations （P>0.05）. Conclusion 2D-SWE has a better diagnostic efficacy than the above seven serological models in determining liver fibrosis stage. The serological models have a certain diagnostic value， among which APRI and S index have a relatively high diagnostic value. There is no significant difference between 2D-SWE and 2D-SWE combined with serological models， and such combinations cannot significantly improve diagnostic efficiency. Therefore， further studies are needed to explore new combinations of diagnostic methods. -
Key words:
- Chronic Hepatitis B /
- Liver Fibrosis /
- Elasticity Imaging Techniques /
- Biopsy， Needle
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图 2 2D-SWE和血清学模型单独诊断肝纤维化的ROC曲线
注： a，S≥2期；b，S≥3期；c，S=4期。
Figure 2. ROC curves of 2D-SWE and serological models for the diagnosis of liver fibrosis
图 3 2D-SWE联合APRI诊断肝纤维化的ROC曲线
注： a，S≥2期；b，S≥3期；c，S=4期。
Figure 3. ROC curve of 2D-SWE combined with APRI in diagnosis of liver fibrosis
图 4 2D-SWE联合S指数诊断肝纤维化的ROC曲线
注： a，S≥2期；b，S≥3期；c，S=4期。
Figure 4. ROC curve of 2D-SWE combined with S index in diagnosis of liver fibrosis
表 1 患者基础情况
Table 1. Patient basic information table
项目 数值 性别（男/女，例） 199/128 年龄（岁） 37（31～46） LSM（kPa） 5.8（4.4～8.0） ALT（IU/L） 35（22～51） AST（IU/L） 28（22～39） GGT（U/L） 26（16～53） Alb（g/L） 43（40～45） Glo（g/L） 30（27～33） PLT（×109/L） 215（180～255） RDW 12.8（12.4～13.3） APRI 0.34（0.24～0.53） FIB-4 0.85（0.63～1.34） AAR 0.88（0.68～1.12） GPR 0.12（0.07～0.31） GP 13.73（11.81～17.26） PRP 0.06（0.05～0.07） S指数 0.07（0.04～0.18） 肝纤维化分期［例（%）］ S0～1 195（59.6） S2 67（20.5） S3 33（10.1） S4 32（9.8） 
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表 2 2D-SWE、各血清学模型与肝纤维化分期的相关性
Table 2. Correlation between 2D-SWE、serological models and hepatic fibrosis stage
项目 r值 P值 LSM 0.741 <0.001 APRI 0.498 <0.001 FIB-4 0.493 <0.001 GPR 0.348 <0.001 GP 0.509 <0.001 RPR 0.285 <0.001 S指数 0.329 <0.001 AAR 0.012 0.835
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表 3 2D-SWE和各血清学模型单独诊断肝纤维化S≥2的效能比较
Table 3. Comparison of the efficacy of 2D-SWE and each serological model in the diagnosis of liver fibrosis S≥2
项目 最佳截断值 AUC 95%CI 敏感度（%） 特异度（%） 2D-SWE 6.90 kPa 0.878 0.838～0.919 71.2 92.3 APRI 0.32 0.788 0.738～0.839 81.1 66.7 FIB-4 0.96 0.710 0.650～0.769 61.4 75.9 AAR 0.83 0.454 0.391～0.517 54.5 58.5 GPR 0.10 0.778 0.727～0.828 84.1 61.0 GP 15.4 0.735 0.677～0.792 61.4 79.0 PRP 0.07 0.694 0.635～0.753 40.9 88.2 S指数 0.08 0.776 0.725～0.826 66.7 76.4
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表 4 2D-SWE和各血清学模型单独诊断肝纤维化S≥3的效能比较
Table 4. Comparison of the efficacy of 2D-SWE and each serological model in the diagnosis of liver fibrosis S≥3
项目 最佳截断值 AUC 95%CI 敏感度（%） 特异度（%） 2D-SWE 7.90 kPa 0.932 0.896～0.968 86.2 90.5 APRI 0.42 0.825 0.765～0.885 78.5 75.2 FIB-4 1.13 0.801 0.737～0.866 70.8 77.5 AAR 1.63 0.516 0.436～0.596 12.3 96.6 GPR 0.16 0.841 0.793～0.890 83.1 72.5 GP 15.63 0.777 0.703～0.852 72.3 76.7 PRP 0.07 0.749 0.678～0.821 53.8 84.0 S指数 0.12 0.846 0.799～0.894 75.4 80.9
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表 5 2D-SWE和各血清学模型单独诊断肝纤维化S=4的效能比较
Table 5. Comparison of the efficacy of 2D-SWE and each serological model in the diagnosis of liver fibrosis S=4
项目 最佳截断值 AUC 95%CI 敏感度（%） 特异度（%） 2D-SWE 9.40 kPa 0.942 0.902～0.982 84.4 93.6 APRI 0.44 0.875 0.820～0.929 90.6 74.6 FIB-4 1.13 0.864 0.792～0.936 87.5 73.9 AAR 1.73 0.550 0.444～0.656 15.6 99.3 GPR 0.22 0.837 0.782～0.891 81.2 74.6 GP 15.79 0.885 0.819～0.952 90.6 74.9 PRP 0.09 0.844 0.767～0.920 78.1 82.4 S指数 0.12 0.835 0.779～0.891 81.2 75.3
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表 6 2D-SWE联合血清学模型诊断肝纤维化的效能比较
Table 6. Comparison of efficacy of 2D-SWE combined serological model in the diagnosis of liver fibrosis
项目 肝纤维化分期 AUC 95%CI 2D-SWE联合APRI S≥2 0.887 0.847～0.927 S≥3 0.938 0.904～0.972 S=4 0.950 0.915～0.985 2D-SWE联合S指数 S≥2 0.879 0.838～0.919 S≥3 0.935 0.900～0.971 S=4 0.941 0.902～0.980
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