Bathena Sai Praneeth R, Thakare Rhishikesh, Gautam Nagsen, Mukherjee Sandeep, Olivera Marco, Meza Jane, Alnouti Yazen
*Department of Pharmaceutical Sciences, College of Pharmacy, Department of Internal Medicine, College of Medicine and Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska 68198
*Department of Pharmaceutical Sciences, College of Pharmacy, Department of Internal Medicine, College of Medicine and Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska 68198.
Toxicol Sci. 2015 Feb;143(2):308-18. doi: 10.1093/toxsci/kfu228. Epub 2014 Oct 24.
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.
肝胆疾病会导致胆汁酸(BAs)在肝脏、全身血液和其他组织中蓄积,从而导致预后不良。胆汁酸谱通过计算描述总胆汁酸和单个胆汁酸的组成、硫酸化和酰胺化的指标来表征。健康受试者与肝胆疾病患者尿胆汁酸谱的比较表明,患者体内单个和总胆汁酸的绝对浓度显著更高。两组之间某些单个胆汁酸的硫酸化百分比有所不同。患者体内总体和大多数单个胆汁酸的酰胺化百分比高于对照组。患者体内初级胆汁酸(鹅去氧胆酸和胆酸)的百分比更高,而次级胆汁酸(脱氧胆酸和石胆酸)的百分比更低。与单个和总胆汁酸的绝对浓度相比,属于酰胺化百分比和组成百分比的胆汁酸指标与终末期肝病模型(MELD)评分和疾病代偿状态所确定的肝病严重程度相关性更好。此外,对应于某些胆汁酸酰胺化百分比和组成百分比的胆汁酸指标在受试者工作特征(ROC)曲线下的面积最大,表明它们在临床上作为诊断生物标志物的效用。此外,患肝病风险的显著增加与胆汁酸指标的变化有关。