乙型肝炎失代偿期肝硬化及慢性肝衰竭患者的呼出气代谢组学差异性分析  

Analysis of Exhaled Gas Metabolites in Patients with Decompensated Cirrhosis and Chronic Liver Failure of Hepatitis B

作　　者：王仲霞 桑秀秀 余思邈 许文涛 苏鹏宇 牛明 王睿林 Wang Zhongxia;Sang Xiuxiu;Yu Simiao;Xu Wentao;Su Pengyu;Niu Ming;Wang Ruilin(Department of Combined TCM and Western Medicine,the 5th Medical Centre,Chinese PLA General Hospital,Beijing 100039,China)

机构地区：[1]解放军总医院第五医学中心/中西医结合诊疗与研究中心

出　　处：《世界科学技术-中医药现代化》2019年第10期2032-2040,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目（81673806）：基于呼出气代谢组学的肝衰竭“肝臭”中医嗅诊辨证客观化研究，负责人：王睿林;军委后勤保障部卫生局保健专项科研课题面上项目（17BJZ53）：基于代谢组学分析的酒精性肝病体质差异研究，负责人：王睿林;中央军委联勤保障部全军医学科技青年培育项目（16QNP151）：参附汤对海水浸泡性低体温症干预作用及其栓剂开发;负责人：牛明

摘　　要：目的研究乙型肝炎失代偿期肝硬化与慢性肝衰竭患者的呼出气代谢组学差异,以探索潜在的能预测严重肝病进展的无创生物标志物。方法采用全二维气相色谱-飞行时间质谱(comprehensive two-dimensional gas chromatography tandem time-of-flight mass spectrometry,GC×GC-TOF-MS)研究乙型肝炎失代偿期肝硬化及慢性肝衰竭两组患者的呼出气代谢产物,以主成分分析(principal component analysis,PCA)和正交偏最小二乘判别法(orthogonal partial least square discriminant analysis,OPLS-DA)比较挥发性有机化合物(volatile organic compound,VOC)的性质及含量,曲线下面积(area under the curve,AUC)和受试者工作特性(receiver operating characteristic,ROC)曲线建立预测模型。结果与失代偿期肝硬化组相比,慢性肝衰竭组的1-dodecanol、1-1-cyclohexen-1-yl-ethanone、1-1-methylethoxy-2-propanone、o-cymene及carbon dioxide含量明显降低。ROC曲线分析显示,十二烷醇(1-dodecanol)可鉴别失代偿期肝硬化与慢性肝衰竭(ROC曲线下面积=0.825),且敏感性77.8%,特异性99.23%。结论十二烷醇可作为一种潜在的生物标志物,预测乙肝失代偿期肝硬化进展为慢性肝衰竭的风险,同时为无创检测方法评估、预测慢性肝病的预后提供物质基础。Objective To study the difference of exhaled gas metabonomics between patients with decompensated hepatitis B cirrhosis and chronic hepatic failure in order to explore potential non-invasive biomarkers for predicting the progression of severe liver diseases.Methods With the advent of comprehensive two-dimensional gas chromatography tandem time-of-flight mass spectrometry(GC×GC-TOF-MS),we studied the difference of exhaled gas metabonomics between patients with decompensated cirrhosis and chronic hepatic failure of hepatitis B.Principal component analysis(PCA)and Orthogonal Partial Least Square Discriminant Analysis(OPLS-DA)were performed to compare the contents of the volatile organic compounds(VOCs).Area under the curve(AUC)and receiver operating characteristic(ROC)curves were used to build a predictive model.Results Compared with decompensated cirrhosis group,the contents of 1-dodecanol,1-1-cyclohexen-1-yl-ethanone,1-1-methylethoxy-2-propanone,o-cymene and carbon dioxide in chronic hepatic failure group were significantly lower.ROC curve analysis showed that 1-dodecanol could identify decompensated cirrhosis and chronic hepatic failure patients(area under ROC curve=0.825),with sensitivity of 77.8%and specificity of 99.23%.Conclusion 1-dodecanol can be used as a potential non-invasive biomarker to predict the risk of hepatitis B decompensated cirrhosis progressing to chronic liver failure,and to provide a foundation for noninvasive detection methods to evaluate and predict the prognosis of chronic liver diseases.

关 键 词：呼出气 代谢组学 失代偿期肝硬化 慢性肝衰竭 

分 类 号：R2-031[医药卫生—中西医结合]