PMID- 34027270 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 2471-254X (Electronic) IS - 2471-254X (Linking) VI - 5 IP - 5 DP - 2021 May TI - Metabolic Profiling of Bile Acids in the Urine of Patients with Alcohol-Associated Liver Disease. PG - 798-811 LID - 10.1002/hep4.1671 [doi] AB - Bile acids (BAs) play important functions in the development of alcohol-associated liver disease (ALD). In the current study, urine BA concentrations in 38 patients with well-described alcohol-associated hepatitis (AH) as characterized by Model for End-Stage Liver Disease (MELD), 8 patients with alcohol-use disorder (AUD), and 19 healthy controls (HCs) were analyzed using liquid chromatography-mass spectrometry. Forty-three BAs were identified, and 22 BAs had significant changes in their abundance levels in patients with AH. The potential associations of clinical data were compared to candidate BAs in this pilot proof-of-concept study. MELD score showed positive correlations with several conjugated BAs and negative correlations with certain unconjugated BAs; taurine-conjugated chenodeoxycholic acid (CDCA) and MELD score showed the highest association. Cholic acid, CDCA, and apocholic acid had nonsignificant abundance changes in patients with nonsevere ALD compared to HCs but were significantly increased in those with severe AH. Receiver operating characteristic analysis showed that the differences in these three compounds were sufficiently large to distinguish severe AH from nonsevere ALD. Notably, the abundance levels of primary BAs were significantly increased while most of the secondary BAs were markedly decreased in AH compared to AUD. Most importantly, the amount of total BAs and the ratio of primary to secondary BAs increased while the ratio of unconjugated to conjugated BAs decreased as disease severity increased. Conclusion: Abundance changes of specific BAs are closely correlated with the severity of AH in this pilot study. Urine BAs (individually or as a group) could be potential noninvasive laboratory biomarkers for detecting early stage ALD and may have prognostic value in AH morbidity. CI - (c) 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases. FAU - He, Liqing AU - He L AD - Department of ChemistryUniversity of LouisvilleLouisvilleKYUSA. AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Hepatobiology and Toxicology ProgramUniversity of LouisvilleLouisvilleKYUSA. AD - Center for Regulatory and Environmental Analytical MetabolomicsUniversity of LouisvilleLouisvilleKYUSA. FAU - Vatsalya, Vatsalya AU - Vatsalya V AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Department of MedicineUniversity of LouisvilleLouisvilleKYUSA. AD - Robley Rex Louisville Veterans Affairs Medical CenterLouisvilleKYUSA. FAU - Ma, Xipeng AU - Ma X AD - Department of ChemistryUniversity of LouisvilleLouisvilleKYUSA. AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Hepatobiology and Toxicology ProgramUniversity of LouisvilleLouisvilleKYUSA. AD - Center for Regulatory and Environmental Analytical MetabolomicsUniversity of LouisvilleLouisvilleKYUSA. FAU - Zhang, Jiayang AU - Zhang J AD - School of DentistryUniversity of LouisvilleLouisvilleKYUSA. FAU - Yin, Xinmin AU - Yin X AD - Department of ChemistryUniversity of LouisvilleLouisvilleKYUSA. AD - Center for Regulatory and Environmental Analytical MetabolomicsUniversity of LouisvilleLouisvilleKYUSA. FAU - Kim, Seongho AU - Kim S AD - Department of OncologyUniversity of LouisvilleLouisvilleKYUSA. AD - Biostatistics Core, Karmanos Cancer InstituteWayne State UniversityDetroitMIUSA. FAU - Feng, Wenke AU - Feng W AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Hepatobiology and Toxicology ProgramUniversity of LouisvilleLouisvilleKYUSA. AD - Department of MedicineUniversity of LouisvilleLouisvilleKYUSA. AD - Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisvilleKYUSA. FAU - McClain, Craig J AU - McClain CJ AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Hepatobiology and Toxicology ProgramUniversity of LouisvilleLouisvilleKYUSA. AD - Department of MedicineUniversity of LouisvilleLouisvilleKYUSA. AD - Robley Rex Louisville Veterans Affairs Medical CenterLouisvilleKYUSA. AD - Biostatistics Core, Karmanos Cancer InstituteWayne State UniversityDetroitMIUSA. FAU - Zhang, Xiang AU - Zhang X AD - Department of ChemistryUniversity of LouisvilleLouisvilleKYUSA. AD - Alcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA. AD - Hepatobiology and Toxicology ProgramUniversity of LouisvilleLouisvilleKYUSA. AD - Center for Regulatory and Environmental Analytical MetabolomicsUniversity of LouisvilleLouisvilleKYUSA. AD - Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisvilleKYUSA. LA - eng GR - K23 AA029198/AA/NIAAA NIH HHS/United States GR - P20 GM113226/GM/NIGMS NIH HHS/United States GR - P50 AA024337/AA/NIAAA NIH HHS/United States GR - R01 AA023190/AA/NIAAA NIH HHS/United States PT - Journal Article DEP - 20210120 PL - United States TA - Hepatol Commun JT - Hepatology communications JID - 101695860 PMC - PMC8122376 EDAT- 2021/05/25 06:00 MHDA- 2021/05/25 06:01 PMCR- 2021/01/20 CRDT- 2021/05/24 08:18 PHST- 2020/08/14 00:00 [received] PHST- 2020/11/02 00:00 [revised] PHST- 2020/12/17 00:00 [accepted] PHST- 2021/05/24 08:18 [entrez] PHST- 2021/05/25 06:00 [pubmed] PHST- 2021/05/25 06:01 [medline] PHST- 2021/01/20 00:00 [pmc-release] AID - 02009842-202105000-00008 [pii] AID - HEP41671 [pii] AID - 10.1002/hep4.1671 [doi] PST - epublish SO - Hepatol Commun. 2021 Jan 20;5(5):798-811. doi: 10.1002/hep4.1671. eCollection 2021 May.