aMAP、APRI、FIB-4及肝硬度评估乙型肝炎肝硬化患者食管胃静脉曲张程度的价值探讨.pdf

论著141诊断学理论与实践2 0 2 3年第2 2 卷第2 期aMAP、A PRI、FI B-4及肝硬度评估乙型肝炎肝硬化患者食管胃静脉曲张程度的价值探讨安宝燕，郭清，江冯明洋，徐玉敏，蔡伟，谢青，王晖（上海交通大学医学院附属瑞金医院感染科，上海200025)摘要】目的：探讨aMAP(age-male-ALBI-platelet，a M A P)、天门冬氨酸氨基转移酶/血小板比率指数（aspartateaminotransferase-to-platelet ratio index,APRI)、基于4因子的肝纤维化指数(fibrosis index based on the 4 factors，FI B-4)及肝硬度值（liver stiffnessmeasurement，LSM)评估乙型肝炎（乙肝）肝硬化患者食管胃静脉曲张(esophageal gastricvarices,ECV)程度的价值。方法：选取2 0 18 年4月到2 0 2 2 年5月期间在上海交通大学医学院附属瑞金医院确诊并接受治疗的乙肝肝硬化患者114例，对其进行肝功能、血常规、LSM、胃镜等检查，根据计算公式计算aMAP、A PRI、FIB-4。根据胃镜结果将患者分为无EGV组（39例）、轻度EGV组（30 例）、中度EGV组（2 3例）及重度EGV组（2 2 例），比较4组间的aMAP、A PRI、FI B-4。采用受试者操作特征曲线(receiveroperatorcharacteristic curve，RO C曲线）分析aMAP、A PRI、FI B-4及LSM评估乙肝肝硬化患者EGV程度的价值。结果：ECV患者（包括轻度、中度及重度EGV组)的aMAP、A PRI、FI B-4、LSM 均显著高于无EGV的患者，差异有统计学意义(P0.05)。轻度、中度及重度EGV组间的aMAP、A PRI、FI B-4差异均有统计学意义(P0.05);轻度EGV组与中度、重度EGV组间LSM差异有统计学意义(P0.05)。a M A P评估ECV程度的ROC曲线下面积（theareaunderROCcurve，A U RO C)为0.7 6，灵敏度为8 5.9%，特异度为6 5.7%；APRI、FI B-4和LSM评估EGV程度的AUR0C分别为0.8 6、0.8 5、0.7 9，灵敏度分别为8 1.30%、8 2.8 0%、88.40%，特异度分别为8 2.90%、7 7.10%、6 6.8 0%。aMAP、A PRI、FI B-4和LSM对肝硬化患者是否合并ECV有较好诊断价值(P0.05)。a M A P、A PRI、FI B-4对乙肝肝硬化患者的EGV程度有一定诊断价值(P0.05),但特异度较低。结论：aMAP、A PRI、FI B-4及LSM诊断乙肝肝硬化患者伴EGV的价值较高，而aMAP、A PRI 及FIB-4对其EGV程度有一定评估价值，可作为不适合做胃镜患者评估ECV的补充参考，为EGV的预防及治疗提供依据。关键词：食管胃底静脉曲张；aMAP；天门冬氨酸氨基转移酶/血小板比率指数；基于4因子的肝纤维化指数；基于4因子的肝纤维化指数中图分类号：R571*.3文献标志码：A文章编号：16 7 1-2 8 7 0(2 0 2 3)0 2-0 141-0 6D01:10.16150/j.1671-2870.2023.02.006Value of aMAP,APRI,FIB-4 and liver stiffness in predicting the degree of esophageal and gastric varices in pa-tientswithhepatitisBcirrhosisAN Baoyan,GUO Qing,FENG Mingyang,XU Yumin,CAI Wei,XIE Qing,WANG HuiDepartment of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,ChinaAbstract Objective:To explore the predictive value of age-male-ALBI-platelets(aMAP),aspartate aminotransfer-ase-to-platelet ratio index(APRI),fibrosis index based on the 4 factors(FIB-4)and liver stiffness measurement(LSM)onthe degree of esophageal and gastric varices(EGV)in patients with hepatitis B cirrhosis.Methods:One hundred and four-teen patients with hepatitis B cirrhosis in Shanghai Ruijin Hospital from April 2018 to May 2022 were enrolled.Examina-tions including liver function,blood routine,LSM and gastroscopy were performed.aMAP,APRI,and FIB-4 were calcu-lated using the calculation formulas of each model.Based on the results of gastroscopy,the patients were divided into fourgroups:non-EGV group(39 cases),mild EGV group(30 cases),moderate EGV group(23 cases)and severe EGV group(22cases),and aMAP,APRI,FIB-4 between groups were compared.The receiver operator characteristic curve(ROC curve)was used to analyze the predictive value of aMAP,APRI,FIB-4 and LSM on the degree of EGV in patients with hepatitis Bcirrhosis.Results:The aMAP,APRI,FIB-4 and LSM of patients with EGV groups(including mild,moderate and severeEGV groups)were significantly higher than those of the non-EGV group(P0.05).The area under ROC(AUROC)of aMAP基金项目：国家自然科学基金（8 157 0 56 0）通信作者：王晖E-mail:142:JDiagnConcepPract2023,Vol.22,No.2for evaluating the degree of EGV was 0.76,with sensitivity of 85.9%and specificity of 65.7%.The AUROC of APRI,FIB-4and LSM for evaluating the degree of EGV were 0.86,0.85 and 0.79 respectively,and the sensitivities were 81.30%,82.80%and88.40%respectively,and the specificities were 82.90%,77.10%and 66.80%respectively.aMAP,APRI,FIB-4 and LSM have agood predictive value for EGV in patients with liver cirhosis(P0.05).Compared with the aMAP,APRI,FIB-4 and LSM in pa-tients with mild,EGV,the aMAP,APRI and FIB-4 of patients with moderate and severe of ECV were significantly different(P0.05).There was a significant difference in LSM between mild EGV group and moderate-severe group(P0.05).aMAP,APRIand FIB-4 have certain predictive values for the degree of EGV in hepatitis B cirrhosis patients(P0.05),with decreased sensitivi-ty and specificity.Conclusions:aMAP,APRI,FIB-4 and LSM are of high predictive value for the presence of EGV in pa-tients with hepatitis B cirrhosis.aMAP,APRI and FIB-4 have certain predictive values for the degree of ECV and can beused as a supplementary method for the evaluation of EGV by invasive gastroscopy,and can provide the basis for the pre-vention and treatment of EGV.Key words:Esophageal and gastric varices;Age-male-albi-platelets;Aspartate aminotransferase-to-platelet ratio index;Fibrosis index based on the 4 factors;Liver stiffness measurement我国是乙型肝炎（乙肝）高发区，乙肝后肝硬化的发生率达到5%10%。食管胃静脉曲张(esophageal gastric varices,EGV)是乙肝肝硬化患者因门静脉高压出现的严重并发症之一,而EGV引起的消化道出血也是肝硬化患者常见的死亡原因之一，及时了解肝硬化患者的EGV程度,对于降低门静脉压力、预防上消化道出血具有重要意义2。目前，胃镜检查是明确EGV程度的“金标准”3,但由于其为侵人性检查，且存在出血、麻醉意外等风险，导致部分患者依从性差，不能定期复查。因此，临床上需要寻找无创的能及时、准确预测患者EGV程度的检测方法，为肝硬化患者的早期治疗提供依据。aMAP(age-male-ALBI-platelets,aMAP)是由我国学者研发的用于肝细胞癌的预测评分模型 4,其已被证实能够预测肝硬化程度。天门冬氨酸氨基转移酶/血小板比率指数(aspartate aminotransferase-to-plateletratio index，A PRI）、基于4因子的肝纤维化指数(fibrosis index based on the 4 factors,FIB-4)及肝硬度值(liver stiffness measurement,LSM)这3项指标也具有相似的作用 5。众所周知，肝硬化程度与门静脉高压程度及EGV程度呈正相关，所以本研究将以上常用于预测肝硬化程度的指标,用于评估乙肝后肝硬化患者的EGV程度，以期找到能较好替代胃镜检查的无创指标，为临床EGV早期的治疗提供依据。1对象与方法1.1研究对象选取2 0 18 年4月到2 0 2 2 年5月期间在上海瑞金医院确诊并接受治疗的乙肝肝硬化患者114例(非连续病例）。其诊断均符合中华医学会传染病与寄生虫学分会、肝病学分会联合修订的病毒性肝炎防治方案中肝炎肝硬化及慢乙肝的诊断标准。EGV的内镜诊断标准采用中华消化内镜学会在2 0 0 9年制定的食管胃底静脉曲张内镜下分级标准 7。所有患者在本研究开始前已经服用核苷类药物抗病毒治疗大于6 个月，且乙型肝炎病毒(hepatitis Bvirus,HBV)DNA50 IU/mL。本研究排除合并其他病毒感染、恶性肿瘤、自身免疫性肝病、酒精性肝病等的患者。1.2方法1.2.1胃镜检查及实验室检查肝硬化患者人组后，继续予核苷类药物抗病毒治疗，同时对患者进行肝功能、血常规、肝硬度、胃镜检查。根据胃镜结果将患者分为无EGV组、轻度EGV组、中度EGV组及重度EGV组 3。血常规检测采用COULTER?ACT5diffAL系统（贝克曼）。肝肾功能等检测采用全自动生化分析仪CX5PRO（美国贝克曼）检测。肝硬度检测仪器来自法国Echosens公司，胃镜来自日本Olympus公司。1.2.2计算公式aMAP评分的计算公式为，aMAP=10.06x年龄（岁）+0.8 9性别(男性=1,女性=0)+0.48 Ig总胆红素（mol/L)0.66+白蛋白（g/L)（-0.0 8 5)-0.01血小板(10/mm)+7.4/(14.77100)4。A PRI计算公式为，APRI=天门冬氨酸转移酶（aspartatetransferase,AST)(U/L)/AST正常值上限(U/L)/血小板(platelet，PLT)(10%L)10 0。FI B-4计算公式为，FIB-4=年龄（岁)AST(U/L)/(PLT(10%L)ALT(U/)/2)8,143.诊断学理论与实践2 0 2 3年第2 2 卷第2 期1.2.3统计学处理采用SPSS27.0统计学软件进行数据分析，计量资料以(xs)表示,计数资料以 n(%)表示。比较组间计量资料时，资料符合正态分布，进行独立样本t检验，比较计数资料采取检验。以电子胃镜诊断结果为金标准,绘制受试者操作特征曲线(re-ceiver operator characteristic curve,ROC 曲线),并计算曲线下面积(the area under ROC curve,AUROC),评价各指标评估有无EGV及EGV程度的临床价值。P0.05),而无EGV患者的PLT显著高于伴EGV的患者(P0.05)。伴ECV的乙肝肝硬化患者（包括轻度、中度和中度EGV组）的aMAP、A P R I、FIB-4和LSM分别为6 2.52 7.36、1.7 7 0.6 9、5.6 6 3.0 9、17.6 2 7.43,均分别显著高于无EGV组（53.8 36.7 9、0.57 0.37、2.2 12.0 7、10.443.72),差异有统计学意义(P0.01)（见表1)。表1伴或不伴EGV的患者肝功能、aMAP、A P R I、FI B-4及LSM比较Table 1 Comparison of liver function,aMAP,APRI,FIB-4,and LSM between patients with or withoutIndicenon-ECVEGVtPALT(IU/L)25.57 7.1827.93 8.711.520.15AST(IU/L)30.79 6.3238.17 11.201.380.18AKP(IU/L)97.25 37.00101.89 44.391.730.10-GT(IU/L)31.8620.0834.8221.852.110.08PLT(10L)135 6756 465.890.01aMAP53.83 6.7962.52 7.364.910.01APRI0.57 0.371.77 0.696.040.01FIB-42.21 1.075.66 3.095.400.01LSM(kPa)10.44 3.7217.62 7.433.860.01PLT:Platelet;aMAP:age-male-ALBI-platelets;APRI:Aspartate ami-notransferase-to-platelet ratio index;FIB-4:Fibrosis index basedon the4 factors;LSM:Liver stiffness measurement.2.2不同ECV程度患者的各项指标比较比较轻度、中度及重度EGV组的aMAP、A P R I、FIB-4、LSM。结果显示，3组间两两比较，aMAP、APRI、FIB-4差异均有统计学意义(P0.05)。轻度ECV组的平均LSM值为10.44kPa,较中度组及重度组低,差异有统计学意义(P0.05)(见表2)。表2轻度、中度和重度EGV组间的aMAP、A P R I、FI B-4及LSM比较Table 2Comparison of aMAP.APRI,FIB-4 and LSM inpatients with mild,moderate and severe EGVIndiceMild EGV group Moderate EGV group Severe EGV groupaMAP55.914.7463.648.1668.505.34LSM13.385.2119.047.5620.017.46APRI1.150.621.820.872.620.60FIB-44.472.865.864.326.741.93Comparison of aMAP,APRI,FIB-4 and LSM in patients with mild,moderate,and severe EGV showed significant differences in aMAP,APRI,FIB-4 among patients with different degrees of EGV(P0.05).There was a significant difference in LSM between the mild EGV groupand the moderate-severe groups(P0.05).2.3各项指标诊断肝硬化患者伴EGV的效能绘制aMAP、A P R I、FIB-4和LSM诊断肝硬化患者伴EGV的ROC曲线，并计算AUROC。a MA P 的AUR0C为0.7 6,9 5%置信区间为0.6 6 0.8 7,诊断灵敏度为8 5.9%，特异度为6 5.7%。APRI、FI B-4和LSM的AUROC分别为0.8 6、0.8 5、0.7 9,诊断灵敏度分别为8 1.30%、8 2.8 0%、8 8.40%，特异度分别为82.90%、7 7.10%、6 6.8 0%。a MA P、A P R I、FI B-4和LSM在评估肝硬化患者伴EGV均具有较好的诊断价值(P0.05)（见表3、图1)。表3aMAP、A P R I、FI B-4及LSM诊断伴EGV的ROC曲线分析Table 3Analysis of aMAP,APRI,FIB-4,and LSM usingROC curves for distinguising non-EGV from EGV groupSensitivitySpecificigyIndiceAUROC95%CIP(%）(%）aMAP0.760.66-0.8785.9065.700.01APRI0.860.77-0.9481.3082.900.01FIB0.850.77-0.9482.8077.100.01LSM(KPa)0.790.70-0.8888.4066.800.012.5各项指标评估EGV程度的效能采用ROC曲线评估aMAP、A P R I、FI B-4和LSM诊断EGV程度的效能。结果显示，aMAP、A P R I、八C表4aMAP、A P R I、FI B-4及LSM评估EGV程度的ROC144JDiagn ConceptsPract 2023,Vol.22,No.2FIB-4对乙肝肝硬化患者的EGV程度有一定诊断价值(P0.05)(见表4、图2)。1.0aMAP0.8APRI-FIB-4LSM0.6-Reference0.40.20.00.00.20.40.60.81.01-Specificity图1aMAP、A P R I、FI B-4及LSM诊断EGV的ROC曲线分析Figure1ROC curves of aMAP,APRI,FIB-4 and LSMFigure 1ROC curves of aMAP,APRI,FIB-4 and LSMfordiagnosingEGV曲线刀析Table 4Analysis of aMAP,APRI,FIB-4 and LSM ROCcurves in patients with mild,moderate of and severe EGVSensitivitySpecificigyIndiceAUROC95%CIP(%）(%）aMAP0.640.52-0.7490.2048.300.02APRI0.720.62-0.8282.9058.600.01FIB-40.740.64-0.8478.0062.100.01LSM(kPa)0.560.44-0.6797.6027.000.311.0aMAP0.8-APRI-FIB-4LSM0.6Reference0.40.20.00.00.20.40.60.81.01-Specificity图2aMAP、A P R I、FI B-4及LSM评估EGV程度的ROC曲线Figure 2ROC curves of aMAP,APRI,FIB-4,and LSMfor diagnosing degree of EGV3讨论随着乙肝肝硬化患者病情进展，其门脉高压逐渐加重。据报道，每年有15%2 0%的乙肝肝硬化患者因EGV发生上消化道出血，其中2 0%30%的患者在4 6 周内死亡 9 。虽然确诊EGV分级的金标准仍为胃镜检查，但由于我国的乙肝发病率高，患病人数多,而胃镜检查是有创检查，部分患者难以耐受，故在随访中对乙肝患者进行定期胃镜检查受到限制。可见，探索一种无创的ECGV诊断模型对其预防和治疗具有重要的临床意义。3.1aMAP评分aMAP评分已被用于预测肝硬化患者发生肝细胞癌的风险 10。但目前尚无报道将aMAP评分用于评估肝硬化患者是否并发EGV及EGV的程度。本研究显示，伴ECV的乙肝肝硬化患者的aMAP评分显著高于无ECV的患者(P0.01)。R O C 曲线分析结果显示，aMAP在诊断肝硬化患者是否合并ECV中有较好的临床应用价值(P0.01),其诊断灵敏度达到8 5.9%，特异度为6 5.7%。对轻度、中度、重度EGV组3组的aMAP评分进行比较，结果提示，3组间的aMAP评分差异有统计学意义(P0.05)。aMAP在乙肝肝硬化患者的EGV程度评估中有一定的诊断价值(P0.05),其灵敏度达9 0.2%,特异度为48.3%，提示aMAP评分能够较为准确地诊断肝硬化患者是否合并ECV，但对EGV严重程度的判断特异度较差。3.2APRI和FIB-4本研究结果同时提示，APRI、FI B-4在评估乙肝肝硬化患者伴ECV方面具有较好的临床诊断价值(P0.01),AUROC分别为0.8 6、0.8 5，诊断灵敏度较高，分别为8 1.30%、8 2.8 0%，特异度分别为82.90%、7 7.7 0%，与其他研究结果基本一致。且本研究显示,轻度、中度、重度EGV组间的APRI、FIB-4差异有统计学意义(P0.05),这2 项指标评估ECV程度的灵敏度分别为8 2.9 0%、7 8.8 0%，特异度分别为58.6 0%、6 2.10%。以上结果提示，APRI、FI B-4诊断乙肝肝硬化患者有无EGV的价值较高，但对于ECV严重程度的评估灵敏度、特异度较低。3.3LSM瞬时弹性超声成像(Fibroscan)是一种无创超声弹性成像技术，可测量LSM,对肝纤维化程度的判断有重要意义 12-14。研究显示,LSM对肝硬化患者伦理批准及知情同意/EthicsApprovalandPatientConsent所有作者都不存在利益冲突:145诊断学理论与实践2 0 2 3年第2 2 卷第2 期是否有ECV有较好的诊断价值。本研究结果提示，无ECV组LSM显著高于伴EGV组(P0.01)，LSM诊断乙肝肝硬化患者有无EGV的灵敏度为88.40%，特异度为6 6.8 0%。虽然轻度ECV组与中度EGV组、重度EGV组间的LSM差异有统计学意义(P0.05)。可见,LSM评估EGV程度的临床价值较低。综上所述，aMAP、A P R I、FIB-4及LSM对乙肝肝硬化患者伴EGV的诊断价值较高，其中APRI、FIB-4的诊断特异度及灵敏度均较好，而aMAP及LSM的诊断灵敏度较高，但特异度较低。aMAP、APRI及FIB-4对乙肝肝硬化患者的EGV程度有一定评估价值。aMAP、A P R I、FIB-4及LSM可作为是否采用侵人性胃镜评估ECV的补充参考，并能为EGV的预防及治疗提供临床依据。利益冲突说明/ConflictofInterests本研究的实施符合赫尔辛基宣言和上海交通大学医学院附属瑞金医院的相关伦理要求，并取得患者的知情同意和签字。作者贡献/AuthorsContributions王晖负责课题设计，安宝燕负责数据收集及论文撰写；郭清负责联络患者及随访；冯明洋进行数据收集；徐玉敏、蔡伟提供入组患者，谢青进行课题设计及审核。参考文献1 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4年起被评定为中国科技论文统计源期刊（中国科技核心期刊），并被国家科技部中国科技论文与引文数据库(CSTPC)收人。本刊的办刊宗旨是：提高读者的诊断理论水平、诊断技能和拓宽诊断循证思路，提高综合分析能力，为疾病的诊断、鉴别诊断、病情观察和预后判断提供依据。本刊所刊内容包括病史采集、体检方法和有关疾病在放射、超声、核医学、检验、内镜和病理检查中的表现特征和诊断要点等。所设栏目包括述评、专家论坛、论著、研究报告、病例分析、经验介绍、技术方法、综述