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Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.

Publication ,  Journal Article
Wegermann, K; Howe, C; Henao, R; Wang, Y; Guy, CD; Abdelmalek, MF; Diehl, AM; Moylan, CA
Published in: Hepatol Commun
April 2021

Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive biomarkers. The aim of this study was to determine if serum metabolite profiles in patients with NAFLD associate with future liver-related events. We performed a retrospective single-center cohort study of 187 participants with biopsy-proven NAFLD. Metabolomic analysis was performed on serum using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified liver-related events (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary or hepatorenal syndrome) by manual chart review between index biopsy (2007-2013) and April 1, 2018. Generalized linear models and Cox proportional hazards models were used to test the association of metabolites with liver-related events and time to first liver-related event, controlling for covariates and fibrosis stage. Over a mean ± SD follow-up of 6.9 ± 3.2 years, 11 participants experienced 22 liver-related events. Generalized linear models revealed 53 metabolites significantly associated with liver-related events (P < 0.05). In Cox proportional hazards modeling, 69 metabolites were significantly associated with time to future liver-related events (P < 0.05), seven of which met the false discovery rate threshold of 0.10: vitamin E metabolites gamma-carboxyethyl-hydroxychroman (gamma-CEHC) and gamma-CEHC glucuronide; primary bile acid metabolite taurochenodeoxycholate; serotonin metabolite 5-hydroxyindoleacetate; and lipid metabolites (i) 2-hydroxyglutarate, (ii) 3beta,17beta-diol disulfate 1, and (iii) eicosenoyl sphingomyelin. Conclusion: Metabolites of a primary bile acid, vitamin E, and serotonin were associated with future liver-related events. Our results suggest metabolite pathways may be useful for predicting which patients with NAFLD are at higher risk for hepatic decompensation.

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Published In

Hepatol Commun

DOI

EISSN

2471-254X

Publication Date

April 2021

Volume

5

Issue

4

Start / End Page

608 / 617

Location

United States

Related Subject Headings

  • Vitamin E
  • Serotonin
  • Risk Factors
  • Proportional Hazards Models
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Metabolomics
  • Male
  • Linear Models
  • Humans
 

Citation

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Chicago
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MLA
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Wegermann, K., Howe, C., Henao, R., Wang, Y., Guy, C. D., Abdelmalek, M. F., … Moylan, C. A. (2021). Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease. Hepatol Commun, 5(4), 608–617. https://doi.org/10.1002/hep4.1665
Wegermann, Kara, Catherine Howe, Ricardo Henao, Ying Wang, Cynthia D. Guy, Manal F. Abdelmalek, Anna Mae Diehl, and Cynthia A. Moylan. “Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.Hepatol Commun 5, no. 4 (April 2021): 608–17. https://doi.org/10.1002/hep4.1665.
Wegermann K, Howe C, Henao R, Wang Y, Guy CD, Abdelmalek MF, et al. Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease. Hepatol Commun. 2021 Apr;5(4):608–17.
Wegermann, Kara, et al. “Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.Hepatol Commun, vol. 5, no. 4, Apr. 2021, pp. 608–17. Pubmed, doi:10.1002/hep4.1665.
Wegermann K, Howe C, Henao R, Wang Y, Guy CD, Abdelmalek MF, Diehl AM, Moylan CA. Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease. Hepatol Commun. 2021 Apr;5(4):608–617.

Published In

Hepatol Commun

DOI

EISSN

2471-254X

Publication Date

April 2021

Volume

5

Issue

4

Start / End Page

608 / 617

Location

United States

Related Subject Headings

  • Vitamin E
  • Serotonin
  • Risk Factors
  • Proportional Hazards Models
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Metabolomics
  • Male
  • Linear Models
  • Humans