Urinary Metabolite Variation Is Associated with Pathological Progression of the Post-Hepatitis B Cirrhosis Patients
Urinary Metabolite Variation Is Associated with Pathological Progression of the Post-Hepatitis B Cirrhosis Patients
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DOI：
10.1021/pr300337s
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发表时间：
2012-07-01
影响因子：
4.4
通讯作者：
Liu, Ping
中科院分区：
文献类型：
--
作者：
Wang, Xiaoning;Wang, Xiaoyan;Liu, Ping
肝硬化是许多慢性肝脏疾病的常见和最终结果。采用气相色谱-质谱（GC-MS）和超高效液相色谱-飞行时间质谱（UPLC-TOFMS）进行尿液代谢组学研究，以阐明 63 名乙型肝炎后肝硬化患者和 31 名健康对照者发生乙型肝炎后肝硬化的病理生理学基础。除了血常规、肝功能和肾功能测试外，还对尿代谢谱和与肝功能 Child-Pugh (CP) 分级相关的相应差异代谢物进行了表征。代谢物分析中采用了包括主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA）在内的多变量统计工具以及单变量统计方法Wilcoxon-Mann-Whitney检验。还调查了导致健康对照和肝硬化患者之间以及 CP A、B 和 C 级肝硬化之间组间差异的差异代谢物的变化。 α-羟基马尿酸、酪氨酸-β黄素、3-羟基异戊酸、刀豆苷酸、雌酮和甘胆去氧胆酸等六种代谢物在肝硬化CP A、B和C患者中显着改变，反映了氨基酸、胆汁酸、激素和肠道代谢的异常 微生物代谢。结果表明，尿代谢组的动态变化（以一组差异代谢标志物的变化为特征）表明肝功能恶化，突出了它们对肝硬化发展的诊断和预后潜力。
Cirrhosis is a common and terminal outcome of many chronic liver conditions. A urinary metabonomic study using gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOFMS) was carried out to elucidate the pathophysiological basis of posthepatitis B cirrhosis in 63 posthepatitis B cirrhosis patients and 31 health controls. Urinary metabolic profile and corresponding differential metabolites associated with Child-Pugh (CP) grading of liver function were characterized, in addition to the blood routine, liver, and renal function tests. Multivariate statistical tools including principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) were employed in the metabolite analysis along with a univariate statistical method, Wilcoxon-Mann-Whitney test. The alterations of differential metabolites contributing to the intergroup variation between healthy controls and cirrhotic patients, and among cirrhosis of CP grade A, B and C were also investigated. Six metabolites, alpha-hydroxyhippurate, tyrosine-betaxanthin, 3-hydroxyisovalerate, canavaninosuccinate, estrone, and glycoursodeoxycholate, were significantly altered among cirrhotic patients with CP A, B, and C, reflecting abnormal metabolism of amino acid, bile acids, hormones, and intestinal microbial metabolism. The results show that dynamic alteration of urinary metabolome, characterized by the changes of a panel of the differential metabolite markers, is indicative of an exacerbated liver function, highlighting their diagnostic and prognostic potential for the liver cirrhosis development.