Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

Jawaher Abdullah Alamoudi; Wenkuan Li; Nagsen Gautam; Marco Olivera; Jane Meza; Sandeep Mukherjee; Yazen Alnouti

doi:10.4254/wjh.v13.i4.433

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

World J Hepatol. 2021 Apr 27;13(4):433-455. doi: 10.4254/wjh.v13.i4.433.

Authors

Jawaher Abdullah Alamoudi¹, Wenkuan Li¹, Nagsen Gautam¹, Marco Olivera², Jane Meza³, Sandeep Mukherjee⁴, Yazen Alnouti⁵

Affiliations

¹ Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
² Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States.
³ Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, United States.
⁴ Department of Internal Medicine, College of Medicine, Creighton University Medical Center, Omaha, NE 68124, United States.
⁵ Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States. yalnouti@unmc.edu.

Abstract

Background: 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.

Aim: To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Bile acid indices; Bile acids; Biomarker; Diagnosis; Hepatobiliary diseases; Liver diseases.