Article(id=1317885736859324656, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, articleNumber=null, orderNo=null, doi=10.12449/JCH260816, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1770739200000, receivedDateStr=2026-02-11, revisedDate=null, revisedDateStr=null, acceptedDate=1774800000000, acceptedDateStr=2026-03-30, onlineDate=1792138044799, onlineDateStr=2026-10-16, pubDate=1787587200000, pubDateStr=2026-08-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792138044799, onlineIssueDateStr=2026-10-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792138044799, creator=13701087609, updateTime=1792138044799, updator=13701087609, issue=Issue{id=1317885672153797495, tenantId=1146029695717560320, journalId=1316781422847033486, year='2026', volume='42', issue='8', pageStart='1745', pageEnd='2000', issueExtLink='null', onlineDate='null', pubDate='1787587200000', pubDateStr='2026-08-25', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1792138029373, creator='13701087609', updateTime=1792138608261, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1317888100290900262, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1317888100290900263, tenantId=1146029695717560320, journalId=1316781422847033486, issueId=1317885672153797495, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1838, endPage=1844, ext={EN=ArticleExt(id=1317885737140343026, articleId=1317885736859324656, tenantId=1146029695717560320, journalId=1316781422847033486, language=EN, title=Value of two-dimensional shear wave elastography combined with serological markers in the differential diagnosis of primary biliary cholangitis and overlap syndrome, columnId=1317885737043874033, journalTitle=Journal of Clinical Hepatology, columnName=Autoimmune Liver Disease, runingTitle=null, highlight=null, articleAbstract=
Objective

To construct a machine learning model combining two-dimensional shear wave elastography (2D-SWE) and serological markers,and to investigate its clinical value in differentiating primary biliary cholangitis (PBC) from overlap syndrome (OS).

Methods

A total of 199 patients with pathologically confirmed PBC or OS in Nantong Third People’s Hospital from January 2021 to December 2025 were retrospectively enrolled,with 125 patients in the PBC group and 74 in the OS group. The patients were randomly divided into a training set with 139 patients and a test set with 60 patients at a ratio of 7∶3. Related data were collected,including serological markers,conventional two-dimensional ultrasound parameters,and 2D-SWE parameters (including velocity of shear wave [VS] and liver fibrosis index [LFI]). The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to identify independent predictive factors,which were then incorporated into six machine learning models,and 5-fold cross-validation was used for optimization of parameters. The indicators including the area under the receiver operating characteristic curve (AUC) were compared in the test set to determine the best model,and the SHapley additive exPlanations (SHAP) analysis was used for model interpretation.

Results

Female patients accounted for 87.8% in the OS group and 79.2% in the PBC group. Compared with the PBC group,the OS group had significantly higher age,VS,LFI,splenic area,aspartate aminotransferase,total bilirubin,prothrombin time,immunoglobulin G (IgG),and immunoglobulin M (Z=-2.883,-6.524,-4.000,-3.061,-2.194,-2.372,-4.079,-6.964,and -2.709,all P<0.05) and a significantly lower platelet count (Z=4.098,P<0.001),and there were also significant differences between the two groups in the proportion of patients with positive anti-nuclear antibody,fibrosis stage,and inflammation grade (χ2=3.458,63.198,and 101.038,all P<0.05). Variables without multicollinearity were included in the regression analysis,and the multivariate Logistic regression analysis showed that VS (odds ratio [OR]=4.503,95% confidence interval [CI]:1.698 — 11.943,P=0.003),LFI (OR=1.813,95%CI:1.050 — 3.132,P=0.033),and IgG (OR=1.121,95%CI:1.026 — 1.226,P=0.012) were independent predictive factors for differentiating PBC from OS. Six machine learning models were constructed based on these variables,among which the logistic regression model showed the best predictive performance in the test set,with an AUC of 0.881 (95%CI:0.788 — 0.974),a sensitivity of 0.731,and a specificity of 0.794. The SHAP analysis showed that IgG contributed the most to model prediction.

Conclusion

The noninvasive multimodal machine learning model combining 2D-SWE parameters (VS,LFI) and serum IgG can effectively differentiate PBC from OS,providing a reference for clinical decision-making regarding the need for liver biopsy.

, authors=Yanan Sun1, 2, Zixian Wang1, 2, Yichen Gu1, 2, Binbin Wu2, Shuhui Xie2, Jing Wu2, authorsList=Yanan Sun, Zixian Wang, Yichen Gu, Binbin Wu, Shuhui Xie, Jing Wu, authorCompany=null, correspAuthors=Jing Wu, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1317885740428677368, articleId=1317885736859324656, tenantId=1146029695717560320, journalId=1316781422847033486, language=CN, title=二维剪切波弹性成像联合血清学指标对原发性胆汁性胆管炎与重叠综合征的鉴别诊断价值, columnId=1317885737241006323, journalTitle=临床肝胆病杂志, columnName=自身免疫性肝病, runingTitle=null, highlight=null, articleAbstract=
目的

二维剪切波弹性成像(2D-SWE)联合血清学指标构建机器学习模型,探讨其鉴别原发性胆汁性胆管炎(PBC)与重叠综合征(OS)的临床价值。

方法

回顾性纳入2021年1月—2025年12月于南通市第三人民医院经病理证实的199例PBC或OS患者为研究对象,其中PBC组125例、OS组74例。按7∶3的比例随机分为训练集(n=139)与测试集(n=60)。收集血清学指标、常规二维超声及2D-SWE参数[剪切波速度(VS)、肝纤维化指数(LFI)等]。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。通过单因素和多因素Logistic回归筛选独立预测因子,将筛选出的变量纳入6种机器学习模型,通过5折交叉验证优化参数,在测试集中比较受试者操作特征曲线下面积(AUC)等指标确定最优模型,使用沙普利加性解释(SHAP)法分析评价模型。

结果

两组患者均以女性为主(OS组87.8%,PBC组79.2%)。OS组患者的年龄、VS、LFI、脾脏面积、天冬氨酸氨基转移酶、总胆红素、凝血酶原时间、免疫球蛋白(Ig)G及IgM水平均显著高于PBC组(Z值分别为-2.883、-6.524、-4.000、-3.061、-2.194、-2.372、-4.079、-6.964、-2.709,P值均<0.05),血小板计数低于PBC组(Z=4.098,P<0.001);抗核抗体比例、肝纤维化分期及炎症分级在两组间差异均有统计学意义(χ2值分别为3.458、63.198、101.038,P值均<0.05)。将不存在多重共线性的变量纳入回归分析,多因素Logistic回归分析显示,VS[比值比(OR)=4.503,95%置信区间(CI):1.698~11.943,P=0.003]、LFI(OR=1.813,95%CI:1.050~3.132,P=0.033)、IgG(OR=1.121,95%CI:1.026~1.226,P=0.012)是区分PBC与OS的独立预测因子。基于上述变量构建6种机器学习模型,其中逻辑回归模型在测试集中的预测效能最佳,AUC为0.881(95%CI:0.788~0.974),敏感度为0.731,特异度为0.794。SHAP分析显示,IgG对模型预测贡献度最大。

结论

联合2D-SWE参数(VS、LFI)与IgG构建的无创多模态机器学习模型可有效鉴别PBC与OS,为临床决策是否进一步行肝脏活组织检查提供参考依据。

, authors=孙亚楠1, 2, 王子弦1, 2, 顾依晨1, 2, 吴彬彬2, 谢淑慧2, 吴静2, authorsList=孙亚楠, 王子弦, 顾依晨, 吴彬彬, 谢淑慧, 吴静, authorCompany=null, correspAuthors=吴静, authorNote=

作者贡献声明

孙亚楠负责课题设计,数据分析,撰写论文;王子弦、顾依晨负责统计分析及数据采集;吴彬彬、谢淑慧负责数据采集,论文审阅;吴静负责指导和论文修改。

, correspAuthorsNote=
吴静, (ORCID:0000-0002-4037-3712)
Wu Jing, (ORCID:0000-0002-4037-3712)
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DOI: 10.1016/j.anndiagpath.2023.152178., articleTitle=Histology and clinical correlations in autoimmune hepatitis, primary biliary cholangitis, and autoimmune hepatitis-primary biliary cholangitis overlap syndrome, refAbstract=null), Reference(id=1317885749433848135, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, doi=null, pmid=null, pmcid=null, year=2020, volume=52, issue=5, pageStart=555, pageEnd=560, url=null, language=null, rfNumber=18, rfOrder=18, authorNames=Yan Y L, Xing X, Lu Q, journalName=Dig Liver Dis, refType=null, unstructuredReference=Yan Y L, Xing X, Lu Q, et al. Assessment of biopsy proven liver fibrosis by two-dimensional shear wave elastography in patients with primary biliary cholangitis[J]. Dig Liver Dis, 2020, 52(5): 555-560. DOI: 10.1016/j.dld.2020.02.002., articleTitle=Assessment of biopsy proven liver fibrosis by two-dimensional shear wave elastography in patients with primary biliary cholangitis, refAbstract=null), Reference(id=1317885749509345608, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, doi=null, pmid=null, pmcid=null, year=2025, volume=46, issue=7, pageStart=863, pageEnd=868, url=null, language=null, rfNumber=19, rfOrder=19, authorNames=陈蕊, 郑一君, 高志玲, journalName=海军军医大学学报, refType=null, unstructuredReference=陈蕊, 郑一君, 高志玲, 等. 超声联合弹性成像技术评估慢性肝病肝纤维化S2期患者炎症分级的价值[J]. 海军军医大学学报, 2025, 46(7): 863-868. 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DOI: 10.1155/2020/8460883., articleTitle=Predicting liver disease risk using a combination of common clinical markers: A screening model from routine health check-up, refAbstract=null), Reference(id=1317885749744226635, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, doi=null, pmid=null, pmcid=null, year=2022, volume=17, issue=1, pageStart=1550, pageEnd=1558, url=null, language=null, rfNumber=21, rfOrder=22, authorNames=Wang K L, Li Y, Pan J F, journalName=Open Med (Wars), refType=null, unstructuredReference=Wang K L, Li Y, Pan J F, et al. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models[J]. Open Med (Wars), 2022, 17(1): 1550-1558. DOI: 10.1515/med-2022-0526., articleTitle=Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1317885740634198265, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, xref=1, ext=[AuthorCompanyExt(id=1317885740646781178, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, companyId=1317885740634198265, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Medical School of Nantong University,Nantong,Jiangsu 226001,China), AuthorCompanyExt(id=1317885740650975483, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, companyId=1317885740634198265, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1南通大学医学院,江苏 南通 226001)]), AuthorCompany(id=1317885740718084348, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, xref=2, ext=[AuthorCompanyExt(id=1317885740722278653, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, companyId=1317885740718084348, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Department of Ultrasound,Nantong Third Hospital Affiliated to Nantong University (Nantong Third People’s Hospital),Nantong,Jiangsu 226006,China), AuthorCompanyExt(id=1317885740730667262, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, companyId=1317885740718084348, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2南通大学附属南通第三医院(南通市第三人民医院)超声科,江苏 南通 226006)])], figs=[ArticleFig(id=1317885744669118763, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=EN, label=Figure 1, caption=Performance comparison between LR model and other algorithms in distinguishing PBC and OS in the test set, figureFileSmall=lrT0O5DEbidg9iGL7HvjJA==, figureFileBig=PjPJXqa34jOSdZtP7GGsgg==, tableContent=null), ArticleFig(id=1317885744753004844, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=CN, label=图1, caption=测试集中LR模型与其他算法区分PBC和OS的性能比较

注:a,测试集的ROC曲线;b,测试集的决策曲线分析;c,测试集的校准曲线;d,LR模型测试集的混淆矩阵。LR,逻辑回归;SVM,支持向量机;RF,随机森林;ET,额外树;XGBoost,极端梯度提升;LightGBM,轻量梯度提升机;TN,真阴性;FP,假阳性;FN,假阴性;TP,真阳性;PBC,原发性胆汁性胆管炎;OS,重叠综合征;ROC,受试者操作特征曲线;AUC,ROC曲线下面积;CI,置信区间。

, figureFileSmall=lrT0O5DEbidg9iGL7HvjJA==, figureFileBig=PjPJXqa34jOSdZtP7GGsgg==, tableContent=null), ArticleFig(id=1317885745117909293, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=EN, label=Figure 2, caption=SHAP feature analysis of the LR model, figureFileSmall=4rVNT9ipEahIVzChc2UR1Q==, figureFileBig=NhJFeuecMTtgB6kplTz39A==, tableContent=null), ArticleFig(id=1317885745214378286, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=CN, label=图2, caption=LR模型的SHAP特征分析

注:a,SHAP摘要图;b,测试集中1例患者的预测过程。IgG,免疫球蛋白G;VS,剪切波速度;LFI,肝纤维化指数;OS,重叠综合征;LR,逻辑回归;SHAP,沙普利加性解释。

, figureFileSmall=4rVNT9ipEahIVzChc2UR1Q==, figureFileBig=NhJFeuecMTtgB6kplTz39A==, tableContent=null), ArticleFig(id=1317885745281487151, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=EN, label=Table 1, caption=

Comparison of clinical characteristics between the PBC group and OS group

, figureFileSmall=null, figureFileBig=null, tableContent=
变量PBC组(n=125)OS组(n=74)统计值P值
年龄(岁)54.00(22.00~74.00)58.00(26.00~75.00)Z=-2.8830.004
性别[例(%)]χ2=1.8340.177
男26(20.8)9(12.2)
女99(79.2)65(87.8)
体重指数(kg/m2)22.72(15.40~43.25)22.17(16.94~27.97)Z=1.5680.117
VS(m/s)1.72(0.96~3.28)2.25(1.07~3.12)Z=-6.524<0.001
ATT(dB·cm-1·MHz-1)0.54(0.33~0.91)0.53(0.31~0.72)Z=1.2870.198
LFI3.01(0.54~5.06)3.61(1.02~8.07)Z=-4.000<0.001
脾脏面积(mm2)2 507.28(1 226.40~10 267.20)2 939.87(1 402.20~8 437.63)Z=-3.0610.002
门静脉内径(mm)11.44±1.3411.61±1.37t=-0.8460.399
ALT(U/L)90.00(4.00~4 079.00)98.00(12.00~982.00)Z=-0.9600.338
AST(U/L)72.00(17.00~2 733.00)96.00(25.00~1 094.00)Z=-2.1940.028
TBil(μmol/L)17.60(6.10~214.10)21.85(8.20~165.30)Z=-2.3720.018
GGT(U/L)224.00(11.00~3 393.00)206.50(19.00~1 654.00)Z=0.3130.755
ALP(U/L)184.00(33.00~1 549.00)174.50(67.00~824.00)Z=0.0650.949
凝血酶原时间(s)11.40(9.00~15.60)12.30(1.05~17.80)Z=-4.079<0.001
血小板计数(×109/L)177.00(33.00~423.00)138.50(46.00~338.00)Z=4.098<0.001
IgG(g/L)14.30(7.66~42.30)20.45(7.00~53.20)Z=-6.964<0.001
IgM(g/L)2.10(0.35~13.00)3.24(0.42~12.30)Z=-2.7090.007
抗核抗体[例(%)]χ2=3.4580.046
阳性99(79.2)49(66.2)
阴性26(20.8)25(33.8)
抗线粒体抗体2型[例(%)]χ2=0.2830.547
阳性50(40.0)26(35.1)
阴性75(60.0)48(64.9)
肝纤维化分期[例(%)]χ2=63.198<0.001
0~1期60(48.0)2(2.7)
2期33(26.4)14(18.9)
3期24(19.2)33(44.6)
4期8(6.4)25(33.8)
炎症分级[例(%)]χ2=101.038<0.001
0~1级28(22.4)0(0.0)
2级72(57.6)5(6.8)
3级25(20.0)67(90.5)
4级0(0.0)2(2.7)
), ArticleFig(id=1317885745352790320, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=CN, label=表1, caption=

PBC组与OS组患者临床特征比较

, figureFileSmall=null, figureFileBig=null, tableContent=
变量PBC组(n=125)OS组(n=74)统计值P值
年龄(岁)54.00(22.00~74.00)58.00(26.00~75.00)Z=-2.8830.004
性别[例(%)]χ2=1.8340.177
男26(20.8)9(12.2)
女99(79.2)65(87.8)
体重指数(kg/m2)22.72(15.40~43.25)22.17(16.94~27.97)Z=1.5680.117
VS(m/s)1.72(0.96~3.28)2.25(1.07~3.12)Z=-6.524<0.001
ATT(dB·cm-1·MHz-1)0.54(0.33~0.91)0.53(0.31~0.72)Z=1.2870.198
LFI3.01(0.54~5.06)3.61(1.02~8.07)Z=-4.000<0.001
脾脏面积(mm2)2 507.28(1 226.40~10 267.20)2 939.87(1 402.20~8 437.63)Z=-3.0610.002
门静脉内径(mm)11.44±1.3411.61±1.37t=-0.8460.399
ALT(U/L)90.00(4.00~4 079.00)98.00(12.00~982.00)Z=-0.9600.338
AST(U/L)72.00(17.00~2 733.00)96.00(25.00~1 094.00)Z=-2.1940.028
TBil(μmol/L)17.60(6.10~214.10)21.85(8.20~165.30)Z=-2.3720.018
GGT(U/L)224.00(11.00~3 393.00)206.50(19.00~1 654.00)Z=0.3130.755
ALP(U/L)184.00(33.00~1 549.00)174.50(67.00~824.00)Z=0.0650.949
凝血酶原时间(s)11.40(9.00~15.60)12.30(1.05~17.80)Z=-4.079<0.001
血小板计数(×109/L)177.00(33.00~423.00)138.50(46.00~338.00)Z=4.098<0.001
IgG(g/L)14.30(7.66~42.30)20.45(7.00~53.20)Z=-6.964<0.001
IgM(g/L)2.10(0.35~13.00)3.24(0.42~12.30)Z=-2.7090.007
抗核抗体[例(%)]χ2=3.4580.046
阳性99(79.2)49(66.2)
阴性26(20.8)25(33.8)
抗线粒体抗体2型[例(%)]χ2=0.2830.547
阳性50(40.0)26(35.1)
阴性75(60.0)48(64.9)
肝纤维化分期[例(%)]χ2=63.198<0.001
0~1期60(48.0)2(2.7)
2期33(26.4)14(18.9)
3期24(19.2)33(44.6)
4期8(6.4)25(33.8)
炎症分级[例(%)]χ2=101.038<0.001
0~1级28(22.4)0(0.0)
2级72(57.6)5(6.8)
3级25(20.0)67(90.5)
4级0(0.0)2(2.7)
), ArticleFig(id=1317885745507979569, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=EN, label=Table 2, caption=

Univariate and multivariate Logistic regression analysis of factors associated with overlap syndrome

, figureFileSmall=null, figureFileBig=null, tableContent=
变量单因素Logistic回归分析多因素Logistic回归分析
OR(95%CI)P值OR(95%CI)P值
体重指数0.858(0.755~0.974)0.018
VS8.347(3.515~19.823)<0.0014.503(1.698~11.943)0.003
LFI1.856(1.248~2.759)0.0021.813(1.050~3.132)0.033
脾脏面积1.000(1.000~1.001)0.016
凝血酶原时间1.313(1.020~1.689)0.034
血小板计数0.991(0.986~0.997)0.004
IgG1.183(1.092~1.281)<0.0011.121(1.026~1.226)0.012
IgM1.223(1.051~1.424)0.010
), ArticleFig(id=1317885745575088434, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=CN, label=表2, caption=

OS相关因素的单因素与多因素Logistic回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量单因素Logistic回归分析多因素Logistic回归分析
OR(95%CI)P值OR(95%CI)P值
体重指数0.858(0.755~0.974)0.018
VS8.347(3.515~19.823)<0.0014.503(1.698~11.943)0.003
LFI1.856(1.248~2.759)0.0021.813(1.050~3.132)0.033
脾脏面积1.000(1.000~1.001)0.016
凝血酶原时间1.313(1.020~1.689)0.034
血小板计数0.991(0.986~0.997)0.004
IgG1.183(1.092~1.281)<0.0011.121(1.026~1.226)0.012
IgM1.223(1.051~1.424)0.010
), ArticleFig(id=1317885745658974515, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=EN, label=Table 3, caption=

Evaluation of predictive performance of six machine learning models across training and test sets

, figureFileSmall=null, figureFileBig=null, tableContent=
模型集别AUC95%CICV_AUC准确度精准度敏感度特异度F1值
LR训练集0.8440.769~0.9190.8540.7630.6320.7500.7690.686
测试集0.8810.788~0.9740.7670.7310.7310.7940.731
SVM训练集0.8740.806~0.9420.8240.8490.7760.7920.8790.784
测试集0.8410.735~0.9480.7170.7140.5770.8240.638
RF训练集0.9340.883~0.9850.8240.8490.7650.8120.8680.788
测试集0.8260.715~0.9370.8000.7920.7310.8530.760
ET训练集0.8660.795~0.9360.8510.8350.7450.7920.8570.768
测试集0.8670.768~0.9650.7670.7500.6920.8240.720
XGBoost训练集0.9920.974~1.0000.7980.9570.9200.9580.9560.939
测试集0.7790.657~0.9020.6830.6400.6150.7350.627
LightGBM训练集0.9490.904~0.9940.7970.8850.8330.8330.9120.833
测试集0.8030.687~0.9200.7330.7080.6540.7940.680
), ArticleFig(id=1317885745730277684, tenantId=1146029695717560320, journalId=1316781422847033486, articleId=1317885736859324656, language=CN, label=表3, caption=

训练集与测试集中6种机器学习模型的预测能力评估

, figureFileSmall=null, figureFileBig=null, tableContent=
模型集别AUC95%CICV_AUC准确度精准度敏感度特异度F1值
LR训练集0.8440.769~0.9190.8540.7630.6320.7500.7690.686
测试集0.8810.788~0.9740.7670.7310.7310.7940.731
SVM训练集0.8740.806~0.9420.8240.8490.7760.7920.8790.784
测试集0.8410.735~0.9480.7170.7140.5770.8240.638
RF训练集0.9340.883~0.9850.8240.8490.7650.8120.8680.788
测试集0.8260.715~0.9370.8000.7920.7310.8530.760
ET训练集0.8660.795~0.9360.8510.8350.7450.7920.8570.768
测试集0.8670.768~0.9650.7670.7500.6920.8240.720
XGBoost训练集0.9920.974~1.0000.7980.9570.9200.9580.9560.939
测试集0.7790.657~0.9020.6830.6400.6150.7350.627
LightGBM训练集0.9490.904~0.9940.7970.8850.8330.8330.9120.833
测试集0.8030.687~0.9200.7330.7080.6540.7940.680
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二维剪切波弹性成像联合血清学指标对原发性胆汁性胆管炎与重叠综合征的鉴别诊断价值
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孙亚楠 1, 2 , 王子弦 1, 2 , 顾依晨 1, 2 , 吴彬彬 2 , 谢淑慧 2 , 吴静 2
临床肝胆病杂志 | 自身免疫性肝病 2026,42(8): 1838-1844
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临床肝胆病杂志 |自身免疫性肝病 2026 , 42 (8) : 1838 -1844
二维剪切波弹性成像联合血清学指标对原发性胆汁性胆管炎与重叠综合征的鉴别诊断价值
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孙亚楠1, 2, 王子弦1, 2, 顾依晨1, 2, 吴彬彬2, 谢淑慧2, 吴静2
作者信息
  • 1南通大学医学院,江苏 南通 226001
  • 2南通大学附属南通第三医院(南通市第三人民医院)超声科,江苏 南通 226006
通讯作者:
吴静, (ORCID:0000-0002-4037-3712)
Wu Jing, (ORCID:0000-0002-4037-3712)
作者简介:

作者贡献声明

孙亚楠负责课题设计,数据分析,撰写论文;王子弦、顾依晨负责统计分析及数据采集;吴彬彬、谢淑慧负责数据采集,论文审阅;吴静负责指导和论文修改。

Value of two-dimensional shear wave elastography combined with serological markers in the differential diagnosis of primary biliary cholangitis and overlap syndrome
Yanan Sun1, 2, Zixian Wang1, 2, Yichen Gu1, 2, Binbin Wu2, Shuhui Xie2, Jing Wu2
Affiliations
  • 1Medical School of Nantong University,Nantong,Jiangsu 226001,China
  • 2Department of Ultrasound,Nantong Third Hospital Affiliated to Nantong University (Nantong Third People’s Hospital),Nantong,Jiangsu 226006,China
出版时间: 2026-08-25 doi: 10.12449/JCH260816
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目的

二维剪切波弹性成像(2D-SWE)联合血清学指标构建机器学习模型,探讨其鉴别原发性胆汁性胆管炎(PBC)与重叠综合征(OS)的临床价值。

方法

回顾性纳入2021年1月—2025年12月于南通市第三人民医院经病理证实的199例PBC或OS患者为研究对象,其中PBC组125例、OS组74例。按7∶3的比例随机分为训练集(n=139)与测试集(n=60)。收集血清学指标、常规二维超声及2D-SWE参数[剪切波速度(VS)、肝纤维化指数(LFI)等]。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。通过单因素和多因素Logistic回归筛选独立预测因子,将筛选出的变量纳入6种机器学习模型,通过5折交叉验证优化参数,在测试集中比较受试者操作特征曲线下面积(AUC)等指标确定最优模型,使用沙普利加性解释(SHAP)法分析评价模型。

结果

两组患者均以女性为主(OS组87.8%,PBC组79.2%)。OS组患者的年龄、VS、LFI、脾脏面积、天冬氨酸氨基转移酶、总胆红素、凝血酶原时间、免疫球蛋白(Ig)G及IgM水平均显著高于PBC组(Z值分别为-2.883、-6.524、-4.000、-3.061、-2.194、-2.372、-4.079、-6.964、-2.709,P值均<0.05),血小板计数低于PBC组(Z=4.098,P<0.001);抗核抗体比例、肝纤维化分期及炎症分级在两组间差异均有统计学意义(χ2值分别为3.458、63.198、101.038,P值均<0.05)。将不存在多重共线性的变量纳入回归分析,多因素Logistic回归分析显示,VS[比值比(OR)=4.503,95%置信区间(CI):1.698~11.943,P=0.003]、LFI(OR=1.813,95%CI:1.050~3.132,P=0.033)、IgG(OR=1.121,95%CI:1.026~1.226,P=0.012)是区分PBC与OS的独立预测因子。基于上述变量构建6种机器学习模型,其中逻辑回归模型在测试集中的预测效能最佳,AUC为0.881(95%CI:0.788~0.974),敏感度为0.731,特异度为0.794。SHAP分析显示,IgG对模型预测贡献度最大。

结论

联合2D-SWE参数(VS、LFI)与IgG构建的无创多模态机器学习模型可有效鉴别PBC与OS,为临床决策是否进一步行肝脏活组织检查提供参考依据。

原发性胆汁性胆管炎  /  重叠综合征  /  机器学习  /  弹性成像技术  /  免疫球蛋白G
Objective

To construct a machine learning model combining two-dimensional shear wave elastography (2D-SWE) and serological markers,and to investigate its clinical value in differentiating primary biliary cholangitis (PBC) from overlap syndrome (OS).

Methods

A total of 199 patients with pathologically confirmed PBC or OS in Nantong Third People’s Hospital from January 2021 to December 2025 were retrospectively enrolled,with 125 patients in the PBC group and 74 in the OS group. The patients were randomly divided into a training set with 139 patients and a test set with 60 patients at a ratio of 7∶3. Related data were collected,including serological markers,conventional two-dimensional ultrasound parameters,and 2D-SWE parameters (including velocity of shear wave [VS] and liver fibrosis index [LFI]). The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to identify independent predictive factors,which were then incorporated into six machine learning models,and 5-fold cross-validation was used for optimization of parameters. The indicators including the area under the receiver operating characteristic curve (AUC) were compared in the test set to determine the best model,and the SHapley additive exPlanations (SHAP) analysis was used for model interpretation.

Results

Female patients accounted for 87.8% in the OS group and 79.2% in the PBC group. Compared with the PBC group,the OS group had significantly higher age,VS,LFI,splenic area,aspartate aminotransferase,total bilirubin,prothrombin time,immunoglobulin G (IgG),and immunoglobulin M (Z=-2.883,-6.524,-4.000,-3.061,-2.194,-2.372,-4.079,-6.964,and -2.709,all P<0.05) and a significantly lower platelet count (Z=4.098,P<0.001),and there were also significant differences between the two groups in the proportion of patients with positive anti-nuclear antibody,fibrosis stage,and inflammation grade (χ2=3.458,63.198,and 101.038,all P<0.05). Variables without multicollinearity were included in the regression analysis,and the multivariate Logistic regression analysis showed that VS (odds ratio [OR]=4.503,95% confidence interval [CI]:1.698 — 11.943,P=0.003),LFI (OR=1.813,95%CI:1.050 — 3.132,P=0.033),and IgG (OR=1.121,95%CI:1.026 — 1.226,P=0.012) were independent predictive factors for differentiating PBC from OS. Six machine learning models were constructed based on these variables,among which the logistic regression model showed the best predictive performance in the test set,with an AUC of 0.881 (95%CI:0.788 — 0.974),a sensitivity of 0.731,and a specificity of 0.794. The SHAP analysis showed that IgG contributed the most to model prediction.

Conclusion

The noninvasive multimodal machine learning model combining 2D-SWE parameters (VS,LFI) and serum IgG can effectively differentiate PBC from OS,providing a reference for clinical decision-making regarding the need for liver biopsy.

Primary Biliary Cholangitis  /  Overlap Syndrome  /  Machine Learning  /  Elasticity Imaging Techniques  /  Immunoglobulin G
孙亚楠, 王子弦, 顾依晨, 吴彬彬, 谢淑慧, 吴静. 二维剪切波弹性成像联合血清学指标对原发性胆汁性胆管炎与重叠综合征的鉴别诊断价值. 临床肝胆病杂志, 2026 , 42 (8) : 1838 -1844 . DOI: 10.12449/JCH260816
Yanan Sun, Zixian Wang, Yichen Gu, Binbin Wu, Shuhui Xie, Jing Wu. Value of two-dimensional shear wave elastography combined with serological markers in the differential diagnosis of primary biliary cholangitis and overlap syndrome[J]. Journal of Clinical Hepatology, 2026 , 42 (8) : 1838 -1844 . DOI: 10.12449/JCH260816
原发性胆汁性胆管炎(primary biliary cholangitis,PBC)是一种慢性自身免疫性肝内胆汁淤积性疾病[1],自身免疫性肝炎(autoimmune hepatitis,AIH)则以免疫介导的肝细胞损伤为特征[2]。二者同属自身免疫性肝病(autoimmune liver disease,AILD)的独立亚型,但可在同一患者中同时或相继出现,形成重叠综合征(overlap syndrome,OS)[3]。OS患者肝脏炎症和纤维化进展较PBC[4]与AIH[5]更显著,临床结局更差。目前,OS的诊断必须依赖肝脏活组织检查,但其存在有创、采样误差和重复性差等不足[6]。二维剪切波弹性成像(two-dimensional shear wave elastography,2D-SWE)是一种无创、可重复的超声技术,能够定量评估肝纤维化程度[7]。近年来,机器学习逐渐应用于医学影像与临床数据分析[8],在肝脏结节良恶性鉴别与肝硬化风险评估中展示出良好潜力[9-10]。然而,目前尚缺乏能够有效识别OS的非侵入性工具。
基于此,本研究探索整合2D-SWE与血清指标构建机器学习模型,以区分PBC与OS,旨在识别存在或高度倾向OS表型的患者,为临床决策及个体化随访管理提供参考依据。
选取2021年1月—2025年12月于南通市第三人民医院接受肝脏活组织检查并经病理确诊的PBC与OS患者为研究对象。纳入标准:(1)年龄≥18岁;(2)PBC与OS的诊断遵循欧洲肝病学会指南[1];(3)肝脏活组织检查前未接受过熊去氧胆酸或免疫抑制治疗。排除标准:(1)合并其他肝病,如病毒性肝炎、非酒精性脂肪性肝病等;(2)肝脏活组织检查标本质量不可靠或病理诊断不明确;(3)临床或超声数据缺失;(4)脾脏已切除。
采用Aloka ARIETTA 850系统,凸阵探头(频率1~6 MHz),由两名高年资医师行常规二维超声和2D-SWE检查,后立即行肝脏活组织检查。检查前患者空腹≥4 h,取平卧位,于平静呼吸时瞬间屏气采集图像。2D-SWE检测时,取样框置于肝右叶被膜下1~2 cm(最深≤5 cm),连续测量5次取中位数。记录剪切波速度(velocity of shear wave,VS)、声衰减系数、肝纤维化指数(liver fibrosis index,LFI)、杨氏模量、纤维化指数及炎症活动指数。常规超声参数包括门静脉内径、脾静脉内径、脾脏长径及厚度,各参数均在标准切面下测量3次取平均值[11]。脾脏面积(mm2)[12]=0.8×脾脏厚度(mm)×脾脏长径(mm)。
收集患者的一般资料及肝脏活组织检查前1周内的实验室指标[天冬氨酸氨基转移酶、丙氨酸氨基转移酶、总胆红素、γ-谷氨酰转移酶、碱性磷酸酶、免疫球蛋白(immunoglobulin,Ig)G、抗核抗体及抗线粒体抗体2型]。肝纤维化分期与炎症分级采用Scheuer系统定义[13]。
采用Python 3.13软件进行统计分析。符合正态分布的计量资料以x¯±s表示,两组间比较采用成组t检验;非正态分布的计量资料以M(P25~P75)表示,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Spearman相关性分析和多重共线性检验排除冗杂变量,将单因素分析中P<0.05的变量纳入多因素Logistic回归(Enter法)筛选独立预测因子。利用scikit-learn工具包构建6种机器学习模型,包括逻辑回归(logistic regression,LR)、支持向量机、随机森林、额外树、极端梯度提升及轻量梯度提升机。通过5折交叉验证对训练集进行内部验证。在测试集中,通过受试者操作特征曲线(receiver operator characteristic curve,ROC 曲线)下面积(area under the curve,AUC)、敏感度、特异度、校准曲线及决策曲线评估模型性能。P<0.05为差异有统计学意义。
共纳入199例患者,其中PBC组125例,OS组74例。两组患者在患病年龄、VS、LFI、脾脏面积、天冬氨酸氨基转移酶、总胆红素、凝血酶原时间、血小板计数、IgG、IgM、抗核抗体比例、肝纤维化分期与炎症分级的差异均有统计学意义(P值均<0.05)(表1)。
结合相关性分析与临床意义,排除与VS高度相关的杨氏模量、纤维化指数及炎症活动指数(r值分别为0.991、0.918、0.904,P值均<0.001)以及与脾脏面积强相关的脾静脉内径(r=0.650,P<0.001)。多重共线性分析显示,剩余变量不存在明显共线性。将单因素分析中P<0.05的8个变量纳入多因素Logistic回归,最终确定VS、LFI和IgG为区分PBC与OS的独立预测因子(P值均<0.05),其中VS预测效力最强(比值比=4.503)(表2)。
所有患者按7∶3的比例随机分为训练集(139例)和测试集(60例)。以VS、LFI和IgG为输入特征,经Z-score标准化后,构建LR、支持向量机、随机森林、额外树、极端梯度提升及轻量梯度提升机6种机器学习模型。在训练集中以5折交叉验证的AUC均值(cross-validation_AUC,CV_AUC)评估模型稳定性,并在测试集进行性能评估。结果显示(表3),LR模型的CV_AUC为0.854,测试集中AUC达0.881(图1a),敏感度为0.731,特异度为0.794,整体判别性能最优且稳定。综合判别能力、稳定性及可解释性,选择LR模型为最终分析模型。
决策曲线分析显示,LR模型的临床净收益最佳(图1b);校准曲线显示,LR模型预测结果与病理之间的一致性良好(图1c);混淆矩阵显示,LR模型对PBC与OS具有稳健的区分能力(图1d)。
采用沙普利加性解释(SHapley Additive exPlanations,SHAP)法对各变量的重要性进行评价。SHAP摘要图显示,IgG对模型预测的总体贡献度最高,其次为VS、LFI(图2a)。此外,各变量的SHAP值随特征取值呈现相对一致的单调变化趋势,未见明显方向性冲突,提示模型决策逻辑具有良好的临床可解释性。图2b的瀑布图展示了测试集中1例患者的预测过程,模型预测其是OS的概率为0.997,与病理诊断结果一致。
既往研究多聚焦于AILD单一亚型的临床或影像特征,对不同表型的系统比较相对有限。有研究指出,OS患者的转氨酶和IgG水平与PBC患者存在显著差异[4],与本研究结果一致。Yan等[14]报道,OS患者初诊时即有相当比例已存在显著纤维化甚至肝硬化。本研究中,OS组患者肝硬化(纤维化4期)的比例达33.8%,这可能与AILD早期症状隐匿有关,提示在初诊阶段引入无创影像学评估的必要性。
进一步分析发现,VS、LFI及IgG是预测OS的独立变量。IgG升高是诊断OS的核心标准之一,与疾病活动及预后相关[15]。SHAP分析显示其对模型的贡献度最高。但部分PBC患者不合并AIH时亦可出现IgG升高[16],提示单一血清指标在鉴别OS时存在局限。VS、LFI可反映肝脏硬度,与IgG代表的免疫炎症活动互补,有助于实现更全面的病情评估。值得注意的是,VS在多因素分析中效应量最大,提示肝纤维化是PBC谱系患者表型识别的重要风险因素,对于IgG处于临界水平但肝硬度较高的患者,建议进一步行肝脏活组织检查以避免漏诊。
本研究发现,OS组患者的VS显著高于PBC组患者,其原因可能在于OS不仅存在PBC典型的胆管损伤和纤维化,同时还叠加了AIH样界面性肝炎,导致肝组织炎症活动度更高、坏死范围更广[17]。已有研究证实,2D-SWE测得的肝硬度值与肝纤维化分期具有良好相关性[14],并在AILD中具有较高的诊断效能[18]。此外,肝硬度值还可能受炎症活动的影响。研究显示,VS在慢性肝病S2期纤维化患者中与炎症分级存在相关性(r=0.404)[19]。因此,本研究中VS在两组间的显著差异,既可能反映纤维化程度差异,也可间接体现炎症活动水平的差异。
既往Wang等[20]基于有限的社会人口学和临床参数建立了AILD人群筛查模型,而本研究聚焦于识别AILD中预后较差的OS个体,实现了更精准的风险评估。近期另一项研究基于抗干燥综合征A抗体、抗核点蛋白100抗体、脾肿大及IgG构建LR模型[21],区分PBC与OS的AUC为0.777 8。与之相比,本研究引入弹性参数进行综合评估,模型在测试集中的AUC达0.881,判别效能更优,为鉴别PBC与OS提供了极具潜力的新工具。
在临床实践中,对于初诊为PBC但伴有IgG或转氨酶明显升高的患者,需鉴别是否合并AIH;对于不适宜行肝穿刺者,该模型可用于初步评估OS的可能性。对熊去氧胆酸应答不佳的PBC患者,若模型提示OS概率较高,可更积极地建议行肝脏活组织检查以明确诊断,尽早启动免疫抑制治疗。由于AIH可能在疾病进展过程中逐渐显现[16],本模型亦可作为PBC患者的随访工具。
本研究存在一些局限性。首先,为单中心回顾性设计,样本量有限,可能增加过拟合风险并影响参数估计的稳定性,尽管采用交叉验证在一定程度上保证了模型的稳健性,但其普适性仍需多中心前瞻性队列进一步验证。其次,肝脏活组织检查的取材及阅片者间的差异可能影响病理分期准确性。最后,2D-SWE测量存在操作者及设备依赖性,模型的推广有赖于各中心检查流程的标准化。此外,未来可进一步整合治疗前后VS、IgG等动态指标,以拓展模型在预后评估中的应用价值。
综上所述,本研究基于VS、LFI和IgG构建的机器学习模型,尤其是LR算法,能有效鉴别PBC与OS,为PBC谱系患者的无创评估提供了可行工具,有助于患者获得早期精准治疗,并辅助肝脏活组织检查决策判断。

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2026年第42卷第8期
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doi: 10.12449/JCH260816
  • 接收时间:2026-02-11
  • 首发时间:2026-10-16
  • 出版时间:2026-08-25
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  • 收稿日期:2026-02-11
  • 录用日期:2026-03-30
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    1南通大学医学院,江苏 南通 226001
    2南通大学附属南通第三医院(南通市第三人民医院)超声科,江苏 南通 226006

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吴静, (ORCID:0000-0002-4037-3712)
Wu Jing, (ORCID:0000-0002-4037-3712)
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