Published online Apr 27, 2021. doi: 10.4254/wjh.v13.i4.433
Peer-review started: January 5, 2021
First decision: January 25, 2021
Revised: February 11, 2021
Accepted: March 22, 2021
Article in press: March 22, 2021
Published online: April 27, 2021
Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis.
To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.
We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.
Total and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases.
BA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.
Core Tip: We have developed the concept of “bile acids (BA) indices” based on the detailed quantitative analysis of the urinary BA profile in patients with cholestatic liver diseases. We demonstrated the use of BA indices as diagnostic biomarkers for cholestatic liver diseases. BA indices had much lower inter- and intra-individual variability compared to absolute concentrations of the total and individual BA. In addition, BA indices demonstrated high area under the receiver operating characteristic curves, and changes of BA indices were associated with the risk of having a liver disease as determined by the logistic regression analysis.