Urinary Bile Acids as Biomarkers for Liver Diseases II. Signature Profiles in Patients

被引:36
作者
Bathena, Sai Praneeth R. [1 ]
Thakare, Rhishikesh [1 ]
Gautam, Nagsen [1 ]
Mukherjee, Sandeep [2 ]
Olivera, Marco [2 ]
Meza, Jane [3 ]
Alnouti, Yazen [1 ]
机构
[1] Univ Nebraska Med Ctr, Dept Pharmaceut Sci, Coll Pharm, Omaha, NE 68198 USA
[2] Univ Nebraska Med Ctr, Dept Internal Med, Coll Med, Omaha, NE 68198 USA
[3] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth, Omaha, NE 68198 USA
关键词
hepatobiliary diseases; bile acids; bile acid sulfation; bile acid amidation; biomarker; HUMAN SMALL-INTESTINE; INTRAHEPATIC CHOLESTASIS; HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; HEPATOBILIARY DISEASES; URSODEOXYCHOLIC ACID; LITHOCHOLIC ACID; BILIARY ATRESIA; DIAGNOSTIC-TEST; GASTRIC BYPASS;
D O I
10.1093/toxsci/kfu228
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Hepatobiliary diseases result in the accumulation of bile acids (BAs) in the liver, systemic blood, and other tissues leading to an unfavorable prognosis. The BA profile was characterized by the calculation of indices that describe the composition, sulfation, and amidation of total and individual BAs. Comparison of the urinary BA profiles between healthy subjects and patients with hepatobiliary diseases demonstrated significantly higher absolute concentrations of individual and total BAs in patients. The percentage sulfation of some individual BAs were different between the two groups. The percentage amidation of overall and most individual BAs was higher in patients than controls. The percentage of primary BAs (CDCA and CA) was higher in patients, whereas the percentage of secondary BAs (DCA and LCA) was lower in patients. BA indices belonging to percentage amidation and percentage composition were better associated with the severity of the liver disease as determined by the model for end-stage liver disease (MELD) score and disease compensation status compared with the absolute concentrations of individual and total BAs. In addition, BA indices corresponding to percentage amidation and percentage composition of certain BAs demonstrated the highest area under the receiver operating characteristic (ROC) curve suggesting their utility as diagnostic biomarkers in clinic. Furthermore, significant increase in the risk of having liver diseases was associated with changes in BA indices.
引用
收藏
页码:308 / 318
页数:11
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