Utility of Metabolomic Biomarkers to Identify Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients

Christopher J. Mowry; Cristina Alonso; Marta Iruarrizaga-Lejarreta; Pablo Ortiz; Josh Levitsky; Mary Rinella

doi:10.1097/TXD.0000000000001227

Utility of Metabolomic Biomarkers to Identify Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients

Christopher J. Mowry, Cristina Alonso, Marta Iruarrizaga-Lejarreta, Pablo Ortiz, Josh Levitsky^*, Mary Rinella^*

^*Corresponding author for this work

Medicine, Hepatology Division

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Background. Nonalcoholic fatty liver disease (NAFLD) is a rising indication for liver transplantation (LT). Identification of NAFLD recurrence and those at risk for more progressive disease after LT remains elusive as the diagnosis requires biopsy, which is invasive and impractical for serial monitoring. We therefore aimed to identify metabolites in the blood associated with recurrent NAFLD that could potentially be used for detection and monitoring. Methods. This cross-sectional pilot study included 37 LT recipients who underwent simultaneous liver biopsy and plasma collection for metabolomic analysis. Metabolic profiles were compared between patients with recurrent NAFLD, normal liver (negative control), and acute rejection (rejection control). Results. Univariate analysis revealed 14 metabolites that were significantly altered in patients with recurrence of NAFLD compared with negative controls and 19 compared with rejection controls (P<0.05). In addition, metabolomic profiling identified 16 metabolites that distinguished nonalcoholic fatty liver versus nonalcoholic steatohepatitis. Metabolite class trends among patients with recurrent NAFLD following LT were consistent with prior metabolomics data in patients with NAFLD in the non-LT setting. Conclusions. In conclusion, we identified candidate metabolites that could be used in the clinical setting to noninvasively identify recurrent NAFLD and differentiate NAFL from the more progressive nonalcoholic steatohepatitis. Further investigation with a larger sample size is warranted to validate these results.

Original language	English (US)
Pages (from-to)	E784
Journal	Transplantation Direct
Volume	7
Issue number	12
DOIs	https://doi.org/10.1097/TXD.0000000000001227
State	Published - Nov 5 2021

Funding

This study was supported by grants from the Digestive Health Foundation and Northwestern Medicine Transplant Endowment. This study was supported by grants from the Digestive Health Foundation and Northwestern Medicine Transplant Endowment. We would also like to thank the Northwestern University Transplant Outcomes Research Collaborative and AST Transplantation and Immunology Research Network Summer Internship Research Program for their support. We thank One Way Liver Metabolomics for material in kind.

ASJC Scopus subject areas

Transplantation

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10.1097/TXD.0000000000001227

Cite this

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title = "Utility of Metabolomic Biomarkers to Identify Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients",

abstract = "Background. Nonalcoholic fatty liver disease (NAFLD) is a rising indication for liver transplantation (LT). Identification of NAFLD recurrence and those at risk for more progressive disease after LT remains elusive as the diagnosis requires biopsy, which is invasive and impractical for serial monitoring. We therefore aimed to identify metabolites in the blood associated with recurrent NAFLD that could potentially be used for detection and monitoring. Methods. This cross-sectional pilot study included 37 LT recipients who underwent simultaneous liver biopsy and plasma collection for metabolomic analysis. Metabolic profiles were compared between patients with recurrent NAFLD, normal liver (negative control), and acute rejection (rejection control). Results. Univariate analysis revealed 14 metabolites that were significantly altered in patients with recurrence of NAFLD compared with negative controls and 19 compared with rejection controls (P<0.05). In addition, metabolomic profiling identified 16 metabolites that distinguished nonalcoholic fatty liver versus nonalcoholic steatohepatitis. Metabolite class trends among patients with recurrent NAFLD following LT were consistent with prior metabolomics data in patients with NAFLD in the non-LT setting. Conclusions. In conclusion, we identified candidate metabolites that could be used in the clinical setting to noninvasively identify recurrent NAFLD and differentiate NAFL from the more progressive nonalcoholic steatohepatitis. Further investigation with a larger sample size is warranted to validate these results.",

author = "Mowry, {Christopher J.} and Cristina Alonso and Marta Iruarrizaga-Lejarreta and Pablo Ortiz and Josh Levitsky and Mary Rinella",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.",

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language = "English (US)",

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AU - Mowry, Christopher J.

AU - Alonso, Cristina

AU - Iruarrizaga-Lejarreta, Marta

AU - Ortiz, Pablo

AU - Levitsky, Josh

AU - Rinella, Mary

N1 - Publisher Copyright: © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

PY - 2021/11/5

Y1 - 2021/11/5

N2 - Background. Nonalcoholic fatty liver disease (NAFLD) is a rising indication for liver transplantation (LT). Identification of NAFLD recurrence and those at risk for more progressive disease after LT remains elusive as the diagnosis requires biopsy, which is invasive and impractical for serial monitoring. We therefore aimed to identify metabolites in the blood associated with recurrent NAFLD that could potentially be used for detection and monitoring. Methods. This cross-sectional pilot study included 37 LT recipients who underwent simultaneous liver biopsy and plasma collection for metabolomic analysis. Metabolic profiles were compared between patients with recurrent NAFLD, normal liver (negative control), and acute rejection (rejection control). Results. Univariate analysis revealed 14 metabolites that were significantly altered in patients with recurrence of NAFLD compared with negative controls and 19 compared with rejection controls (P<0.05). In addition, metabolomic profiling identified 16 metabolites that distinguished nonalcoholic fatty liver versus nonalcoholic steatohepatitis. Metabolite class trends among patients with recurrent NAFLD following LT were consistent with prior metabolomics data in patients with NAFLD in the non-LT setting. Conclusions. In conclusion, we identified candidate metabolites that could be used in the clinical setting to noninvasively identify recurrent NAFLD and differentiate NAFL from the more progressive nonalcoholic steatohepatitis. Further investigation with a larger sample size is warranted to validate these results.

AB - Background. Nonalcoholic fatty liver disease (NAFLD) is a rising indication for liver transplantation (LT). Identification of NAFLD recurrence and those at risk for more progressive disease after LT remains elusive as the diagnosis requires biopsy, which is invasive and impractical for serial monitoring. We therefore aimed to identify metabolites in the blood associated with recurrent NAFLD that could potentially be used for detection and monitoring. Methods. This cross-sectional pilot study included 37 LT recipients who underwent simultaneous liver biopsy and plasma collection for metabolomic analysis. Metabolic profiles were compared between patients with recurrent NAFLD, normal liver (negative control), and acute rejection (rejection control). Results. Univariate analysis revealed 14 metabolites that were significantly altered in patients with recurrence of NAFLD compared with negative controls and 19 compared with rejection controls (P<0.05). In addition, metabolomic profiling identified 16 metabolites that distinguished nonalcoholic fatty liver versus nonalcoholic steatohepatitis. Metabolite class trends among patients with recurrent NAFLD following LT were consistent with prior metabolomics data in patients with NAFLD in the non-LT setting. Conclusions. In conclusion, we identified candidate metabolites that could be used in the clinical setting to noninvasively identify recurrent NAFLD and differentiate NAFL from the more progressive nonalcoholic steatohepatitis. Further investigation with a larger sample size is warranted to validate these results.

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Utility of Metabolomic Biomarkers to Identify Nonalcoholic Fatty Liver Disease in Liver Transplant Recipients

Abstract

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