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.
[1]Shanghai Univ Tradit Chinese Med, E Inst Shanghai Municipal Educ Comm, Shanghai 201203, Peoples R China.
[2]Shuguang Hosp, Inst Liver Dis, Minist Educ, Key Lab Liver & Kidney Dis, Shanghai 201204, Peoples R China.
[3]Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Minist Educ, Key Lab Syst Biomed, Shanghai 200240, Peoples R China.
[4]Univ N Carolina Greensboro, Dept Nutr, Kannapolis, NC 28081 USA.
[5]Shanghai Univ Tradit Chinese Med, Ctr Chinese Med Therapy & Syst Biol, Shanghai 201204, Peoples R China.
[6]Tsinghua Univ, Dept Chem, Minist Educ, Key Lab Bioorgan Phosphorus Chem & Chem Biol, Beijing 100083, Peoples R China.
[7]Jiangxi Univ Tradit Chinese Med, Sch Pharm, Nanchang 440004, Jiangxi, Peoples R China.
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