Abstract | OBJECTIVE: METHODS: Among sequential subjects (n=102) undergoing diagnostic liver biopsy, we examined the associations of a broad panel of BAs with distinct histopathological features of NAFLD, the presence of NASH, and their associations with genetic variants linked to NAFLD and NASH. RESULTS: Plasma BA alterations were observed through the entire spectrum of NAFLD, with several glycine conjugated forms of the BAs demonstrating significant associations with higher grades of inflammation and fibrosis. Plasma 7-Keto-DCA levels showed the strongest associations with advanced stages of hepatic fibrosis [odds ratio(95% confidence interval)], 4.2(1.2-16.4), NASH 24.5(4.1-473), and ballooning 18.7(4.8-91.9). Plasma 7-Keto-LCA levels were associated with NASH 9.4(1.5-185) and ballooning 5.9(1.4-28.8). Genetic variants at several NAFLD/NASH loci were nominally associated with increased levels of 7-Keto- and glycine-conjugated forms of BAs, and the NAFLD risk allele at the TRIB1 locus showed strong tendency toward increased plasma levels of GCA (p=0.02) and GUDCA (p=0.009). CONCLUSIONS: Circulating bile acid levels are associated with histopathological and genetic determinants of the transition from simple hepatic steatosis into NASH. Further studies exploring the potential involvement of bile acid metabolism in the development and/or progression of distinct histopathological features of NASH are warranted.
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Authors | Nisreen Nimer, Ibrahim Choucair, Zeneng Wang, Ina Nemet, Lin Li, Janet Gukasyan, Taylor L Weeks, Naim Alkhouri, Nizar Zein, W H Wilson Tang, Michael A Fischbach, J Mark Brown, Hooman Allayee, Srinivasan Dasarathy, Valentin Gogonea, Stanley L Hazen |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 116
Pg. 154457
(03 2021)
ISSN: 1532-8600 [Electronic] United States |
PMID | 33275980
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Adult
- Aged
- Bile Acids and Salts
(blood, metabolism)
- Biopsy
- Case-Control Studies
- Disease Progression
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Humans
- Male
- Metabolome
(physiology)
- Metabolomics
- Middle Aged
- Non-alcoholic Fatty Liver Disease
(blood, genetics, pathology)
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