Clinical Significance of Serum Bile Acid Profiles in Fatty Liver

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2024 Dec 26

PMID 39722833

Authors

Hao-Yue Sun

Le-Can Wu

Meng-Jie Xu

En-Dian Zheng

Ying-Cong Yu

Yi Ye

Affiliations

Soon will be listed here.

Abstract

Objective: This study aims to investigate the alterations in serum bile acid profiles among individuals with fatty liver (including non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) and evaluate their clinical significance when combined with liver enzyme levels.

Methods: A cohort of 110 individuals with fatty liver (including non-alcoholic fatty liver 58 individuals and alcoholic fatty liver 52 individuals) was selected from the Department of Gastroenterology at Wenzhou People's Hospital between January 2021 and December 2022, while a control group of 66 healthy individuals was recruited from the hospital's health examination center during the same period. Clinical data and blood samples were collected from all participants. Serum bile acid profiles were quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Statistical analysis was conducted in conjunction with liver enzyme indicators.

Results: In the NAFL group, GCA, TCA, and TCDCA levels were significantly elevated compared to the control group, with GCA (AUC 0.754, sensitivity 0.707, specificity 0.712), TCA (AUC 0.770, sensitivity 0.724, specificity 0.712), and TCDCA (AUC 0.782, sensitivity 0.810, specificity 0.652) showing strong diagnostic value. In the AFL group, TCDCA, TCA, GCA, TUDCA, and GUDCA were significantly elevated, with AUC values ranging from 0.848 to 0.912. Among these, TUDCA had the highest sensitivity (0.885) and specificity (0.773) for AFL diagnosis. TUDCA (sensitivity 0.615, specificity 0.897) was the key bile acid distinguishing AFL from NAFL, with an optimal cut-off of 36.33 nmol/L. These bile acids show significant diagnostic potential for differentiating NAFL and AFL.

Conclusion: The bile acid profiles in both NAFL and AFL patients show changes, which hold potential clinical significance and may serve as serum biomarkers to differentiate NAFL from AFL.

References

Chiang J . Bile acid metabolism and signaling. Compr Physiol. 2013; 3(3):1191-212. PMC: 4422175. DOI: 10.1002/cphy.c120023. View

Jiao N, Baker S, Chapa-Rodriguez A, Liu W, Nugent C, Tsompana M . Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut. 2017; 67(10):1881-1891. DOI: 10.1136/gutjnl-2017-314307. View

Safari Z, Gerard P . The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci. 2019; 76(8):1541-1558. PMC: 11105223. DOI: 10.1007/s00018-019-03011-w. View

Wang Y, Chen W, Yu D, Forman B, Huang W . The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor κ light-chain enhancer of activated B cells (NF-κB) in mice. Hepatology. 2011; 54(4):1421-32. PMC: 3184183. DOI: 10.1002/hep.24525. View

Spatz M, Ciocan D, Merlen G, Rainteau D, Humbert L, Gomes-Rochette N . Bile acid-receptor TGR5 deficiency worsens liver injury in alcohol-fed mice by inducing intestinal microbiota dysbiosis. JHEP Rep. 2021; 3(2):100230. PMC: 7903352. DOI: 10.1016/j.jhepr.2021.100230. View

Rumgay H, Shield K, Charvat H, Ferrari P, Sornpaisarn B, Obot I . Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol. 2021; 22(8):1071-1080. PMC: 8324483. DOI: 10.1016/S1470-2045(21)00279-5. View

Nimer N, Choucair I, Wang Z, Nemet I, Li L, Gukasyan J . Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression. Metabolism. 2020; 116:154457. PMC: 7856026. DOI: 10.1016/j.metabol.2020.154457. View

Rinella M, Neuschwander-Tetri B, Siddiqui M, Abdelmalek M, Caldwell S, Barb D . AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023; 77(5):1797-1835. PMC: 10735173. DOI: 10.1097/HEP.0000000000000323. View

Jonas W, Schurmann A . Genetic and epigenetic factors determining NAFLD risk. Mol Metab. 2020; 50:101111. PMC: 8324682. DOI: 10.1016/j.molmet.2020.101111. View

10.

Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M . A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003; 278(11):9435-40. DOI: 10.1074/jbc.M209706200. View

11.

Xu J, Xie S, Chi S, Zhang S, Cao J, Tan B . Protective effects of taurocholic acid on excessive hepatic lipid accumulation regulation of bile acid metabolism in grouper. Food Funct. 2022; 13(5):3050-3062. DOI: 10.1039/d1fo04085e. View

12.

Zhou Y, Lu W, Yang G, Chen Y, Cao J, Zhou C . Bile acid metabolism and liver fibrosis following treatment with bifid triple viable capsules in nonalcoholic fatty liver disease. Am J Transl Res. 2022; 13(12):13485-13497. PMC: 8748085. View

13.

Riazi K, Azhari H, Charette J, Underwood F, King J, Afshar E . The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022; 7(9):851-861. DOI: 10.1016/S2468-1253(22)00165-0. View

14.

Xie G, Wang X, Huang F, Zhao A, Chen W, Yan J . Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int J Cancer. 2016; 139(8):1764-75. PMC: 5493524. DOI: 10.1002/ijc.30219. View

15.

Xie G, Zhong W, Li H, Li Q, Qiu Y, Zheng X . Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. FASEB J. 2013; 27(9):3583-93. PMC: 3752538. DOI: 10.1096/fj.13-231860. View

16.

Rotman Y, Sanyal A . Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2016; 66(1):180-190. DOI: 10.1136/gutjnl-2016-312431. View

17.

Reinehr R, Graf D, Haussinger D . Bile salt-induced hepatocyte apoptosis involves epidermal growth factor receptor-dependent CD95 tyrosine phosphorylation. Gastroenterology. 2003; 125(3):839-53. DOI: 10.1016/s0016-5085(03)01055-2. View

18.

Stofan M, Guo G . Bile Acids and FXR: Novel Targets for Liver Diseases. Front Med (Lausanne). 2020; 7:544. PMC: 7516013. DOI: 10.3389/fmed.2020.00544. View

19.

Lefevre A, DECARLI L, Lieber C . Effect of ethanol on cholesterol and bile acid metabolism. J Lipid Res. 1972; 13(1):48-55. View

20.

Yerushalmi B, Dahl R, Devereaux M, Gumpricht E, Sokol R . Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. Hepatology. 2001; 33(3):616-26. DOI: 10.1053/jhep.2001.22702. View