Metabolic Profiling Of Bile Acids In Urine Of Patients With Acute Alcohol Associated Hepatitis

Background: Bile acids (BAs) play an important role in the development of alcohol associated liver disease (ALD) In the current study, the urine BA concentrations in patients with acute alcohol associated hepatitis (AAH) were analyzed by solid-phase extract (SPE) liquid chromatographymass spectrometry (LC-MS), and the urine BA levels were compared between healthy controls and AAH patients with different severity were compared Methods: Baseline urine samples were collected from 28 well-characterized AAH patients (Model for End-Stage Liver Disease [MELD] score: non-severe [MELD20]), 3 alcohol use disorder (AUD) patients, and 9 healthy controls (HC) SPE-LCMS analysis identified a total of 29 BAs from urine samples Urine was used because it is non-invasive and represents an easily accessible biological fluid in this time of COVID-19 restrictions Results: Seventeen BAs of 29 BAs analyzed had significant changes in their abundance levels within the AAH patient cohort Associations of demographic, drinking, and clinical data were analyzed with candidate BAs MELD scores showed positive correlations with certain conjugated BAs and negative correlations with the few unconjugated BAs;taurineconjugated CDCA and MELD showed highest association 6,7-diketolithocholic acid and apocholic acid had nonsignificant abundance changes in the non-severe AAH patients compared to HC but were significantly increased in severe AAH AUROC analysis showed that the differences of these two compounds was sufficiently large to distinguish severe AAH from non-severe AAH (Fig 1) Notably, the abundance levels of glycine-conjugated DCA and glycohyocholic acid were significantly increased, while those of deoxycholic acid and 23-nordeoxycholic acid were markedly decreased, in AAH patients compared to AUD subjects Importantly, we observed that the abundance levels of most conjugated BAs increased by disease stage in a stepwise manner, and some unconjugated BAs decreased in AAH patients who did not survive Conclusion: The abundance changes of specific BAs are closely correlated with the severity of AAH Urine primary BAs were increased in AAH and secondary BAs were decreased in diseases, demonstrating that BAs (individually or as a group) could be potential laboratory biomarkers for detecting early stage of AAH, and may have prognostic values in AAH morbidity