Article(id=1203057882133651491, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.02.0151, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1616688000000, receivedDateStr=2021-03-26, revisedDate=null, revisedDateStr=null, acceptedDate=1649347200000, acceptedDateStr=2022-04-08, onlineDate=1764760950834, onlineDateStr=2025-12-03, pubDate=1677513600000, pubDateStr=2023-02-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764760950834, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764760950834, creator=13701087609, updateTime=1764760950834, updator=13701087609, issue=Issue{id=1203057879566737430, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='2', pageStart='123', pageEnd='244', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764760950222, creator=13701087609, updateTime=1764762101198, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203062707223241334, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203062707223241335, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203057879566737430, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=151, endPage=156, ext={EN=ArticleExt(id=1203057882418864167, articleId=1203057882133651491, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=High-risk factors of esophago-gastric fundal varices in patients with HBV-related compensated cirrhosis and diagnostic value of multiple models, columnId=1203057881600974876, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=The diagnosis, treatment and prognosis of chronic hepatitis B, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the risk factors of esophago-gastric fundal varices (EGV) in patients with hepatitis B virus (HBV)-related compensated cirrhosis, and to compare the clinical performance of multiple noninvasive prediction models for EGV evaluation. Methods A retrospective analysis was performed on the clinical data of patients with hepatitis B cirrhosis from two centers from January 2017 to December 2019. All patients underwent biochemical examination, gastroscopy, and liver stiffness measurement (LSM). AST-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4) and LSM-spleen diameter (SD)-to-platelet ratio score (LSPS) were calculated. According to the results of gastroscopy, they were divided into EGV and non-EGV group. The high-risk factors of EGV were explored by binary logistic regression. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to evaluate the clinical performance of each indicator in predicting EGV. Results A total of 470 patients were enrolled, including 292 in the non-EGV group and 178 in the EGV group. Logistic regression analysis showed low PLT (platelet)(OR=0.99, 95%CI 0.98-0.99), high SD (spleen diameter)(OR=1.02, 95%CI 1.01-1.03) and high LSM(OR=1.04, 95%CI 1.02-1.07) were high risk factors for EGV (all P<0.05). The AUC of LSPS in predicting EGV [0.75(95%CI 0.71-0.79)] was significantly higher than that of PLT [0.72(95%CI 0.67-0.76)], SD [0.69(95%CI 0.64-0.73)], LSM [0.67(95%CI 0.63-0.72)], APRI [0.69(95%CI 0.65-0.74)] and FIB-4 [0.66(95%CI 0.62-0.71)](P<0.05). The LSPS score in EGV group was significantly higher than that in non-EGV group [2.7(1.3, 5.0) vs. 1.0(0.5, 1.7), P<0.001]. With the aggravation of EGV, LSPS score showed an upward trend (r=0.426, P<0.001). The cutoff value of LSPS for high risk of EGV was >3.5, the corresponding specificity and positive predictive value (PPV) ratio were 93.6% and 79.8% respectively. The cutoff value of LSPS for low risk of EGV was<1.3, its sensitivity and negative predictive value were 75.5% and 81.1% respectively. Conclusions Incorporating three risk factors including low PLT, high LSM and SD, the LSPS in predicting EGV in patients with compensated hepatitis B cirrhosis is better than ARPI, FIB-4, or LSM, and can reduce the need for gastroscopy.

, correspAuthors=Chun-Yan Wang, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨乙型肝炎肝硬化代偿期患者食管-胃底静脉曲张(EGV)的高危因素,并比较多种无创预测模型评估EGV的临床价值。方法 回顾性分析2017年1月-2019年12月于解放军总医院第五医院中心及天津市第二人民医院诊治的乙型肝炎肝硬化代偿期患者的临床资料。所有患者均接受常规生化检测、胃镜检查及FibroTouch检测,并计算谷草转氨酶与血小板比值指数(APRI)、纤维化4因子指数(FIB-4)及肝硬度-脾直径-血小板评分(LSPS)。根据胃镜结果将患者分为EGV组与无EGV组。采用单因素及logistic回归分析EGV的高危因素,绘制受试者工作特征(ROC)曲线,并计算曲线下面积(AUC),评价各指标诊断EGV的价值。结果 470例乙型肝炎肝硬化代偿期患者中,EGV组178例,无EGV组292例。Logistic回归分析结果显示,低血小板(PLT)(OR=0.99,95%CI 0.98~0.99)、高脾直径(SD)(OR=1.02,95%CI 1.01~1.03)及高肝硬度值(LSM)(OR=1.04,95%CI 1.02~1.07)是EGV的高危因素(P<0.05)。LSPS预测EGV的AUC[0.75(95%CI 0.71~0.79)]明显高于PLT[0.72(95%CI 0.67~0.76)]、SD[0.69(95%CI 0.64~0.73)]、LSM[0.67(95%CI 0.63~0.72)]、APRI[0.69(95%CI 0.65~0.74)]及FIB-4[0.66(95%CI 0.62~0.71)],差异均有统计学意义(P<0.05)。EGV组的LSPS值为2.7(1.3,5.0),高于无EGV组的1.0(0.5,1.7),差异有统计学意义(P<0.001);随着EGV程度的加重,LSPS值呈上升趋势(r=0.426,P<0.001)。LSPS值>3.5提示乙型肝炎肝硬化代偿期有EGV风险,特异度为93.6%,阳性预测值为79.8%;LSPS值<1.3提示EGV风险小,敏感度为75.5%,阴性预测值为81.1%。结论 基于PLT、LSM及SD构建的LSPS可用于评估乙型肝炎肝硬化代偿期患者EGV的发生风险,较ARPI、FIB-4、LSM的预测价值更高,可使部分患者免于内镜检查。

, correspAuthors=王春艳, authorNote=null, correspAuthorsNote=
王春艳,E-mail:
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杜雅萌,硕士研究生,主要从事临床预后模型构建等方面的研究

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杜雅萌,硕士研究生,主要从事临床预后模型构建等方面的研究

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J Gastroenterol Hepatol, 2018, 33(10):1696-1706., articleTitle=Accuracy of liver stiffness, spleen stiffness, and LS-spleen diameter to platelet ratio score in detection of esophageal varices: systemic review and meta-analysis, refAbstract=null)], funds=[Fund(id=1203057891247874541, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, awardId=2018JM12603003, language=EN, fundingSource=Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment, China Social Assisstance Foundation(2018JM12603003), fundOrder=null, country=null), Fund(id=1203057891327566322, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, awardId=2018JM12603003, language=CN, fundingSource=中华社会救助基金会菊梅肝胆病防治能力建设专项基金重点项目(2018JM12603003), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1203057883396137042, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, xref=1, ext=[AuthorCompanyExt(id=1203057883404525651, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883396137042, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China), AuthorCompanyExt(id=1203057883412914260, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883396137042, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1解放军总医院第五医学中心肝病医学部,北京 100039)]), AuthorCompany(id=1203057883475828823, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, xref=2, ext=[AuthorCompanyExt(id=1203057883517771866, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883475828823, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Graduate School, Capital Medical University, Beijing 100069, China), AuthorCompanyExt(id=1203057883526160476, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883475828823, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2首都医科大学研究生院,北京 100069)]), AuthorCompany(id=1203057883651989599, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, xref=3, ext=[AuthorCompanyExt(id=1203057883660378209, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883651989599, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3Department of Hepatology, the First People's Hospital of Lanzhou University, Lanzhou, Gansu 730000, China), AuthorCompanyExt(id=1203057883664572514, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883651989599, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3兰州大学第一人民医院肝病科,甘肃兰州 730000)]), AuthorCompany(id=1203057883756847208, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, xref=4, ext=[AuthorCompanyExt(id=1203057883773624425, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883756847208, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=4Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300010, China), AuthorCompanyExt(id=1203057883790401642, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, companyId=1203057883756847208, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=4天津市第二人民医院肝病科,天津 300010)])], figs=[ArticleFig(id=1203057888924230052, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=EN, label=Fig. 1, caption=The ROC curves of various indicators and models for diagnosis of EGV in hepatitis B cirrhosis, figureFileSmall=GKRZQY0QxAZsWH0l9WHa5w==, figureFileBig=bApMyoQoKvE1jUnN0bGzIA==, tableContent=null), ArticleFig(id=1203057889016504749, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=CN, label=图1, caption=相关指标与多种模型诊断乙型肝炎肝硬化EGV的ROC曲线

EGV. 食管胃底静脉曲张;ROC. 受试者工作特征曲线;LSPS. 肝硬度-脾直径-血小板评分;PLT. 血小板;APRI. 谷草转氨酶与血小板比值指数;SD. 脾直径;LSM. 肝硬度值;FIB-4. 纤维化4因子指数

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A. EGV与无EGV比较;B. 不同程度EGV比较;EGV. 食管-胃底静脉曲张;LSPS. 肝硬度-脾直径-血小板评分

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Comparison of clinical characteristics between two groups of patients with HBV-related compensated cirrhosis

, figureFileSmall=null, figureFileBig=null, tableContent=
指标无EGV组(n=292)EGV组(n=178)t/Z/χ2P
年龄(岁,$\bar{x}±s$)49.4±9.948.1±10.71.4150.158
男性[例(%)]201(68.8)147(82.6)10.876<0.001
BMI (kg/m2, $\bar{x}±s$)25.7±14.624.4±3.5–1.6700.095
WBC (×109/L, $\bar{x}±s$)4.8±1.54.1±1.6–5.466<0.001
PLT (×109/L, $\bar{x}±s$)136.5±50.397.3±51.9–8.253<0.001
HGB (g/L, $\bar{x}±s$)143.0±16.4140.7±18.1–1.4660.143
AST [U/L, M(Q1, Q3)]27.0(21.0, 39.2)33.0(24.0, 51.8)–3.4000.001
ALT [U/L, M(Q1, Q3)]27.0(18.8, 45.0)28.0(21.0, 45.8)–1.3770.168
TBIL [μmol/L, M(Q1, Q3)]13.9(10.6, 18.2)17.4(13.1, 25.6)–5.124<0.001
ALB [g/L, M(Q1, Q3)]39.0(37.0, 42.0)39.0(36.0, 43.0)–1.0580.290
HBsAg [U/ml, M(Q1, Q3)]4950.5(2459.0, 6415.5)3805.0(1543.0, 5970.0)–1.9520.051
HBeAg阳性[例(%)]90(30.8)47(26.4)1.4050.307
HBV DNA阳性[例(%)]103(35.3)71(39.9)1.0100.315
HBV DNA* (log10 IU/ml)4.3±1.83.9±1.8–1.3630.173
SD (cm, $\bar{x}±s$)11.5±21.113.5±30.0–6.743<0.001
PVD (mm, $\bar{x}±s$)11.4±1.211.8±1.2–3.637<0.001
LSM [kPa, M(Q1, Q3)]11.6(7.9, 17.0)16.9(10.9, 24.8)–6.406<0.001
), ArticleFig(id=1203057890614534600, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=CN, label=表1, caption=

两组乙型肝炎肝硬化代偿期患者一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标无EGV组(n=292)EGV组(n=178)t/Z/χ2P
年龄(岁,$\bar{x}±s$)49.4±9.948.1±10.71.4150.158
男性[例(%)]201(68.8)147(82.6)10.876<0.001
BMI (kg/m2, $\bar{x}±s$)25.7±14.624.4±3.5–1.6700.095
WBC (×109/L, $\bar{x}±s$)4.8±1.54.1±1.6–5.466<0.001
PLT (×109/L, $\bar{x}±s$)136.5±50.397.3±51.9–8.253<0.001
HGB (g/L, $\bar{x}±s$)143.0±16.4140.7±18.1–1.4660.143
AST [U/L, M(Q1, Q3)]27.0(21.0, 39.2)33.0(24.0, 51.8)–3.4000.001
ALT [U/L, M(Q1, Q3)]27.0(18.8, 45.0)28.0(21.0, 45.8)–1.3770.168
TBIL [μmol/L, M(Q1, Q3)]13.9(10.6, 18.2)17.4(13.1, 25.6)–5.124<0.001
ALB [g/L, M(Q1, Q3)]39.0(37.0, 42.0)39.0(36.0, 43.0)–1.0580.290
HBsAg [U/ml, M(Q1, Q3)]4950.5(2459.0, 6415.5)3805.0(1543.0, 5970.0)–1.9520.051
HBeAg阳性[例(%)]90(30.8)47(26.4)1.4050.307
HBV DNA阳性[例(%)]103(35.3)71(39.9)1.0100.315
HBV DNA* (log10 IU/ml)4.3±1.83.9±1.8–1.3630.173
SD (cm, $\bar{x}±s$)11.5±21.113.5±30.0–6.743<0.001
PVD (mm, $\bar{x}±s$)11.4±1.211.8±1.2–3.637<0.001
LSM [kPa, M(Q1, Q3)]11.6(7.9, 17.0)16.9(10.9, 24.8)–6.406<0.001
), ArticleFig(id=1203057890744558034, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=EN, label=Tab. 2, caption=

Univariate and multivariate logistic regression analysis of EGV risk in HBV-related compensated cirrhosis

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变量单因素分析多因素分析
OR(95%CI)POR(95%CI)P
男性2.15(1.36~3.40)0.0011.51(0.87~2.65)0.146
WBC (×109/L)0.72(0.63~0.83)<0.0011.02(0.85~1.23)0.849
PLT (×109/L)0.98(0.98~0.99)<0.0010.99(0.98~0.99)0.026
AST (U/L)1.00(1.00~1.01)0.1251.00(0.99~1.01)0.896
TBIL (μmol/L)1.02(1.01~1.04)0.0031.01(0.99~1.02)0.498
SD (cm)1.03(1.02~1.04)<0.0011.02(1.01~1.03)0.001
PVD (mm)1.31(1.11~1.55)0.0011.11(0.92~1.35)0.272
LSM (kPa)1.06(1.04~1.09)<0.0011.04(1.02~1.07)0.001
), ArticleFig(id=1203057890874581463, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=CN, label=表2, caption=

乙型肝炎肝硬化代偿期EGV影响因素的单因素与多因素logistic回归分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
变量单因素分析多因素分析
OR(95%CI)POR(95%CI)P
男性2.15(1.36~3.40)0.0011.51(0.87~2.65)0.146
WBC (×109/L)0.72(0.63~0.83)<0.0011.02(0.85~1.23)0.849
PLT (×109/L)0.98(0.98~0.99)<0.0010.99(0.98~0.99)0.026
AST (U/L)1.00(1.00~1.01)0.1251.00(0.99~1.01)0.896
TBIL (μmol/L)1.02(1.01~1.04)0.0031.01(0.99~1.02)0.498
SD (cm)1.03(1.02~1.04)<0.0011.02(1.01~1.03)0.001
PVD (mm)1.31(1.11~1.55)0.0011.11(0.92~1.35)0.272
LSM (kPa)1.06(1.04~1.09)<0.0011.04(1.02~1.07)0.001
), ArticleFig(id=1203057890966856154, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=EN, label=Tab. 3, caption=

Diagnostic accuracy of LSPS for prediction of EGV in hepatitis B cirrhosis

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LSPS截断值敏感度(%)特异度(%)阳性预测值(%)阴性预测值(%)阳性似然比阴性似然比
3.542.593.679.873.16.60.6
1.375.563.155.081.12.00.4
), ArticleFig(id=1203057891092685281, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203057882133651491, language=CN, label=表3, caption=

不同LSPS截断值对乙型肝炎肝硬化代偿期EGV的诊断价值

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LSPS截断值敏感度(%)特异度(%)阳性预测值(%)阴性预测值(%)阳性似然比阴性似然比
3.542.593.679.873.16.60.6
1.375.563.155.081.12.00.4
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乙型肝炎肝硬化代偿期伴食管-胃底静脉曲张的高危因素及多种模型的诊断价值研究
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杜雅萌 1, 2 , 康宁 3 , 赵黎莉 4 , 白硕文 2 , 李倩倩 1 , 牛小霞 1 , 李嘉 4 , 纪冬 1 , 王春艳 1, *
解放军医学杂志 | 慢性乙型肝炎的诊治与预后专题研究 2023,48(2): 151-156
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解放军医学杂志 | 慢性乙型肝炎的诊治与预后专题研究 2023, 48(2): 151-156
乙型肝炎肝硬化代偿期伴食管-胃底静脉曲张的高危因素及多种模型的诊断价值研究
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杜雅萌1, 2, 康宁3, 赵黎莉4, 白硕文2, 李倩倩1, 牛小霞1, 李嘉4, 纪冬1, 王春艳1, *
作者信息
  • 1解放军总医院第五医学中心肝病医学部,北京 100039
  • 2首都医科大学研究生院,北京 100069
  • 3兰州大学第一人民医院肝病科,甘肃兰州 730000
  • 4天津市第二人民医院肝病科,天津 300010
  • 杜雅萌,硕士研究生,主要从事临床预后模型构建等方面的研究

通讯作者:

王春艳,E-mail:
High-risk factors of esophago-gastric fundal varices in patients with HBV-related compensated cirrhosis and diagnostic value of multiple models
Ya-Meng Du1, 2, Ning Kang3, Li-Li Zhao4, Shuo-Wen Bai2, Qian-Qian Li1, Xiao-Xia Niu1, Jia Li4, Dong Ji1, Chun-Yan Wang1, *
Affiliations
  • 1Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
  • 2Graduate School, Capital Medical University, Beijing 100069, China
  • 3Department of Hepatology, the First People's Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
  • 4Department of Hepatology, Tianjin Second People's Hospital, Tianjin 300010, China
出版时间: 2023-02-28 doi: 10.11855/j.issn.0577-7402.2023.02.0151
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目的 探讨乙型肝炎肝硬化代偿期患者食管-胃底静脉曲张(EGV)的高危因素,并比较多种无创预测模型评估EGV的临床价值。方法 回顾性分析2017年1月-2019年12月于解放军总医院第五医院中心及天津市第二人民医院诊治的乙型肝炎肝硬化代偿期患者的临床资料。所有患者均接受常规生化检测、胃镜检查及FibroTouch检测,并计算谷草转氨酶与血小板比值指数(APRI)、纤维化4因子指数(FIB-4)及肝硬度-脾直径-血小板评分(LSPS)。根据胃镜结果将患者分为EGV组与无EGV组。采用单因素及logistic回归分析EGV的高危因素,绘制受试者工作特征(ROC)曲线,并计算曲线下面积(AUC),评价各指标诊断EGV的价值。结果 470例乙型肝炎肝硬化代偿期患者中,EGV组178例,无EGV组292例。Logistic回归分析结果显示,低血小板(PLT)(OR=0.99,95%CI 0.98~0.99)、高脾直径(SD)(OR=1.02,95%CI 1.01~1.03)及高肝硬度值(LSM)(OR=1.04,95%CI 1.02~1.07)是EGV的高危因素(P<0.05)。LSPS预测EGV的AUC[0.75(95%CI 0.71~0.79)]明显高于PLT[0.72(95%CI 0.67~0.76)]、SD[0.69(95%CI 0.64~0.73)]、LSM[0.67(95%CI 0.63~0.72)]、APRI[0.69(95%CI 0.65~0.74)]及FIB-4[0.66(95%CI 0.62~0.71)],差异均有统计学意义(P<0.05)。EGV组的LSPS值为2.7(1.3,5.0),高于无EGV组的1.0(0.5,1.7),差异有统计学意义(P<0.001);随着EGV程度的加重,LSPS值呈上升趋势(r=0.426,P<0.001)。LSPS值>3.5提示乙型肝炎肝硬化代偿期有EGV风险,特异度为93.6%,阳性预测值为79.8%;LSPS值<1.3提示EGV风险小,敏感度为75.5%,阴性预测值为81.1%。结论 基于PLT、LSM及SD构建的LSPS可用于评估乙型肝炎肝硬化代偿期患者EGV的发生风险,较ARPI、FIB-4、LSM的预测价值更高,可使部分患者免于内镜检查。

乙型肝炎  /  肝硬化  /  食管-胃底静脉曲张  /  无创预测模型

Objective To analyze the risk factors of esophago-gastric fundal varices (EGV) in patients with hepatitis B virus (HBV)-related compensated cirrhosis, and to compare the clinical performance of multiple noninvasive prediction models for EGV evaluation. Methods A retrospective analysis was performed on the clinical data of patients with hepatitis B cirrhosis from two centers from January 2017 to December 2019. All patients underwent biochemical examination, gastroscopy, and liver stiffness measurement (LSM). AST-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4) and LSM-spleen diameter (SD)-to-platelet ratio score (LSPS) were calculated. According to the results of gastroscopy, they were divided into EGV and non-EGV group. The high-risk factors of EGV were explored by binary logistic regression. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to evaluate the clinical performance of each indicator in predicting EGV. Results A total of 470 patients were enrolled, including 292 in the non-EGV group and 178 in the EGV group. Logistic regression analysis showed low PLT (platelet)(OR=0.99, 95%CI 0.98-0.99), high SD (spleen diameter)(OR=1.02, 95%CI 1.01-1.03) and high LSM(OR=1.04, 95%CI 1.02-1.07) were high risk factors for EGV (all P<0.05). The AUC of LSPS in predicting EGV [0.75(95%CI 0.71-0.79)] was significantly higher than that of PLT [0.72(95%CI 0.67-0.76)], SD [0.69(95%CI 0.64-0.73)], LSM [0.67(95%CI 0.63-0.72)], APRI [0.69(95%CI 0.65-0.74)] and FIB-4 [0.66(95%CI 0.62-0.71)](P<0.05). The LSPS score in EGV group was significantly higher than that in non-EGV group [2.7(1.3, 5.0) vs. 1.0(0.5, 1.7), P<0.001]. With the aggravation of EGV, LSPS score showed an upward trend (r=0.426, P<0.001). The cutoff value of LSPS for high risk of EGV was >3.5, the corresponding specificity and positive predictive value (PPV) ratio were 93.6% and 79.8% respectively. The cutoff value of LSPS for low risk of EGV was<1.3, its sensitivity and negative predictive value were 75.5% and 81.1% respectively. Conclusions Incorporating three risk factors including low PLT, high LSM and SD, the LSPS in predicting EGV in patients with compensated hepatitis B cirrhosis is better than ARPI, FIB-4, or LSM, and can reduce the need for gastroscopy.

hepatitis B  /  liver cirrhosis  /  esophago-gastric fundal varices  /  noninvasive prediction models
杜雅萌, 康宁, 赵黎莉, 白硕文, 李倩倩, 牛小霞, 李嘉, 纪冬, 王春艳. 乙型肝炎肝硬化代偿期伴食管-胃底静脉曲张的高危因素及多种模型的诊断价值研究. 解放军医学杂志, 2023 , 48 (2) : 151 -156 . DOI: 10.11855/j.issn.0577-7402.2023.02.0151
Ya-Meng Du, Ning Kang, Li-Li Zhao, Shuo-Wen Bai, Qian-Qian Li, Xiao-Xia Niu, Jia Li, Dong Ji, Chun-Yan Wang. High-risk factors of esophago-gastric fundal varices in patients with HBV-related compensated cirrhosis and diagnostic value of multiple models[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (2) : 151 -156 . DOI: 10.11855/j.issn.0577-7402.2023.02.0151
食管-胃底静脉曲张(esophago-gastric fundal varices,EGV)是乙型肝炎肝硬化常见且严重的并发症,其一旦发生出血可能危及患者生命[1-2],因此早期发现EGV至关重要。目前诊断EGV的金标准仍是胃镜检查,我国及美国肝病研究协会均建议初次确诊肝硬化的患者应做胃镜检查,代偿期肝硬化患者应每2~3年进行1次胃镜检查[3-4]。但有研究显示,50%的肝硬化患者在初次确诊后的10年内不会发展为EGV,高危患者仅占所有EGV患者的15%~25%[5-8],因此,对所有肝硬化患者特别是低危人群进行定期的内镜筛查会增加非必要的侵入性手术及额外的经济负担。另外,由于胃镜存在侵入性、费用高及可诱发出血等缺点,患者依从性差,无法作为常规检查反复应用及长期随访。目前已经建立了多种识别是否存在EGV的无创预测模型,包括肝硬度-脾直径-血小板评分(LSPS)、谷草转氨酶与血小板比值指数(APRI)、纤维化4因子指数(FIB-4)等[9]。本研究旨在探讨乙型肝炎肝硬化代偿期患者发生EGV的高危因素,并分析上述预测模型对此类患者的诊断价值。
收集2017年1月-2019年12月于解放军总医院第五医学中心及天津市第二人民医院诊治的470例乙型肝炎肝硬化代偿期患者的临床资料。患者年龄(48.9±10.2)岁,其中男348例(74%),女122例(26%),174例(37.0%)HBV DNA阳性。肝硬化诊断标准参照《慢性乙型肝炎防治指南(2015更新版)》[10]。纳入标准:(1)年龄18~75岁;(2)诊断为乙型肝炎肝硬化;(3)Child-Pugh分级A级;(4)入院2周内完善电子胃镜检查及FibroTouch检测。排除标准:(1)合并其他病毒感染,包括甲、丙、戊型肝炎病毒;(2)酒精性、非酒精性、自身免疫性、药物性及遗传代谢性肝硬化;(3)失代偿期肝硬化,如腹水、EGV破裂出血及肝性脑病等;(4)既往接受过脾切除术、脾栓塞、经颈静脉肝内门体分流术及内镜下治疗等;(5)合并肝癌、肝脏切除史、门静脉血栓或门静脉海绵样变;(6)电子胃镜检查结果记录不详或临床资料不完整。本研究获得解放军总医院第五医院中心伦理委员会批准(2020056D)。
一般资料包括性别、年龄、身高及体重等。实验室指标包括白细胞(white blood cells,WBC)、血小板(platelet,PLT)、血红蛋白(hemoglobin,HGB)、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)、直接胆红素(direct bilirubin,DBIL)、白蛋白(albumin,ALB)、凝血酶原时间(prothrombin time,PT)。根据实验室指标计算APRI、FIB-4。计算公式如下[11]:APRI=(AST/正常值上限×100)/PLT(×109/L)。FIB-4=[年龄×AST(U/L)]/[PLT(×109/L)×$\sqrt{\operatorname{ALT}(\mathrm{U} / \mathrm{L})}$]。
腹部超声检查由具有丰富超声检查经验的医师完成,测定脾直径(spleen diameter,SD)及门静脉内径(portal vein diameter,PVD)。脾直径定义为电子卡钳在图像监视器上脾门水平上的最大纵向尺寸[8]。采用FibroTouch(无锡海斯凯尔医学技术有限公司)检测肝硬度值(liver stiffness measurement,LSM),测量10次后取其中位数。LSPS值=肝硬度值(kPa)×脾直径(cm)/PLT计数(×109/L)[8]。胃镜检查使用日本奥林巴斯电子胃镜Q260。EGV诊断标准参照《肝硬化门静脉高压食管胃静脉曲张出血的防治指南》[3],评估患者有无EGV,并采用我国LDRf标准进行分型。
采用单因素及logistic回归筛选EGV发生的高危因素;采用MedCalc软件绘制受试者工作特征(ROC)曲线,确定曲线下面积(AUC)及诊断界值,并计算相应的灵敏度、特异度、阳性预测值、阴性预测值,比较EGV高危因素与LSPS、APRI、FIB-4无创预测模型对EGV的诊断效能;比较LSPS对不同严重程度EGV的诊断价值,以及不同LSPS截断值对EGV的诊断价值。
采用SPSS 26.0软件进行统计分析。服从正态分布的计量资料以$\bar{x}±s$表示,两组间比较采用独立样本t检验;偏态分布数据以M(Q1Q3)表示,两组间比较采用Mann-Whitney U检验。计数资料以例(%)表示,两组间比较采用χ2检验。采用Spearman相关分析LSPS值与EGV严重程度的相关性。组间AUC的比较采用Z检验。P<0.05为差异有统计学意义。
根据胃镜检查结果,470例患者中无EGV组292例,EGV组178例,其中128例轻度、35例中度、15例重度。两组年龄、BMI、HGB、ALT、ALB、HBsAg、HBeAg及HBV DNA比较差异均无统计学意义(P>0.05),而两组性别、WBC、PLT、AST、TBIL、SD、PVD及LSM比较差异有统计学意义(P<0.05,表1)。
以单因素分析中P<0.05的变量为自变量,以EGV为因变量进行logistic回归分析,结果显示,低PLT、高SD及高LSM是乙型肝炎肝硬化代偿期患者发生EGV的危险因素(P<0.05,表2)。
基于logistic回归分析的结果,将EGV的高危因素PLT、SD、LSM与3个预测模型(LSPS、APRI、FIB-4)进行比较,结果显示,LSPS评估EGV的AUC明显大于PLT、SD、LSM、APRI及FIB-4(图1)。
EGV组的LSPS值为[2.7(1.3,5.0)],明显高于无EGV组的[1.0(0.5,1.7)],差异有统计学意义(P<0.001,图2A);LSPS值随EGV程度的加重而逐渐升高,轻度EGV为1.2(0.6,2.3),中度EGV为4.6(2.9,8.1),重度EGV为5.9(3.0,8.4)。Spearman相关分析显示,LSPS值与EGV严重程度呈正相关(r=0.426,P<0.001,图2B)。ROC曲线分析显示,LSPS值>3.5提示EGV发生风险大,对应的特异度、阳性预测值分别为93.6%、79.8%;LSPS值<1.3提示EGV发生风险小,对应的敏感度、阴性预测值分别为75.5%、81.1%(表3)。本研究中37.7%(177/470)的患者LSPS值低于该阈值1.3。
在我国,乙型肝炎病毒感染是肝硬化最常见的病因。有研究发现,代偿期肝硬化患者的中位生存期可长达12年,而EGV已成为影响代偿期肝硬化患者预后的重要因素[7]。目前胃镜仍然是筛查静脉曲张的重要手段,由于静脉曲张具有变动性,且不同内镜医师对静脉曲张的评判存在差异,导致文献报道的静脉曲张患病率在24%~80%范围内波动[6]。一项来自美国的研究纳入了4230例肝硬化患者,其中仅有约1/3的患者接受了胃镜检查[12]。通过胃镜进行筛查和随访会造成巨大的时间成本和经济负担[13]。如何实现代偿期肝硬化患者的静脉曲张分层管理是目前研究的热点。
2015年版的Baveno Ⅵ共识提出部分代偿期慢性进展期肝病(compensated advanced chronic liver disease,cACLD)患者和Child-Pugh分级A级肝硬化患者不必行胃镜筛查,可通过无创性指标进行随访,如LSM、PLT可用于cACLD患者EGV风险的评估及监测。采用LSM<20 kPa且PLT>150×109/L的标准可使15%~35%的代偿期肝硬化患者免于胃镜检查[14]。既往多项研究表明,LSM及PLT对丙型肝炎肝硬化及酒精性肝硬化患者的EGV风险具有良好的评估效能[15-18],但针对乙型肝炎肝硬化的研究相对较少。本研究通过分析乙型肝炎肝硬化代偿期患者EGV的风险因素,筛选出3个高危因素,即低PLT、高LSM及高SD,其中PLT、LSM与EGV发生风险的关系已被证实[19-20]。SD联合PLT对肝硬化患者EGV的发生风险也有较好的预测价值[19-21]
近年来越来越多的证据显示,单独使用某项指标如LSM、脾硬度、PLT预测EGV风险有一定的局限性,而联合多个指标构建无创预测模型则成为趋势[22-24]。有研究发现,APRI和FIB-4可用于预测EGV,但其预测的准确度差异大、敏感性不足[25-27]。2010年,Kim等[8]首次联合LSM、PLT、SD构建LSPS模型用于预测乙型肝炎肝硬化患者的EGV,结果显示其具有较高的预测价值。荟萃分析也发现LSPS预测静脉曲张的效能优于单独使用LSM,因此,美国肝病研究协会推荐乙型肝炎患者使用LSPS以预测EGV的发生风险[28]。本研究比较了LSPS与LSM、PLT、SD、APRI、FIB-4评估EGV的效能差异,发现LSPS具有最大的AUC。EGV组的LSPS值明显高于无EGV组,且随着EGV严重程度的加重,LSPS值呈上升趋势。有学者提出,当LSPS<3.5可暂时避免胃镜检查,而LSPS>5.5则应行预防性治疗[8]。Abraldes等[7]利用LSPS<1.3预测cACLD患者的静脉曲张风险,结果显示26%的患者低于该阈值,不需要行胃镜筛查。本研究结果显示,当LSPS<1.3时,提示EGV风险低,采用该阈值可使37.7%的代偿期肝硬化患者免于胃镜检查,而当LSPS>3.5时,提示EGV风险较高,需进一步行胃镜评估,与上述研究结果基本一致。
本研究尚存在一定局限性。由于研究对象均为Child-Pugh A级乙型肝炎肝硬化代偿期患者,EGV高风险患者比例较低,因而需要进一步开展多中心大样本的研究,以探索其他分级或病因患者EGV的影响因素及无创模型的评价效能。总之,LSPS可用于预测评估乙型肝炎肝硬化代偿期患者EGV的发生风险,较ARPI、FIB-4、LSM的预测价值更高,可使部分患者免于内镜检查,且便于随访。
  • 中华社会救助基金会菊梅肝胆病防治能力建设专项基金重点项目(2018JM12603003)
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2023年第48卷第2期
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doi: 10.11855/j.issn.0577-7402.2023.02.0151
  • 接收时间:2021-03-26
  • 首发时间:2025-12-03
  • 出版时间:2023-02-28
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  • 收稿日期:2021-03-26
  • 录用日期:2022-04-08
基金
Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment, China Social Assisstance Foundation(2018JM12603003)
中华社会救助基金会菊梅肝胆病防治能力建设专项基金重点项目(2018JM12603003)
作者信息
    1解放军总医院第五医学中心肝病医学部,北京 100039
    2首都医科大学研究生院,北京 100069
    3兰州大学第一人民医院肝病科,甘肃兰州 730000
    4天津市第二人民医院肝病科,天津 300010

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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