Lipidomics-based plasma signature of alcohol-related hepatitis linked to short-term mortality
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction
Severe alcohol-related hepatitis (sAH) is an inflammatory condition with high short-term mortality. Hypothesis-driven approaches have failed to identify effective treatments. Given the role of lipids as inflammatory mediators, this study aimed to identify lipidomic changes and lipid species associated with sAH and mortality risk.
Method
Untargeted lipidomics was performed on serum samples from two cohorts of patients with sAH and decompensated cirrhosis (DC). Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess lipidome changes. Correlations were made with lipoproteins, lipid mediators, cytokines, cytokeratin fragments, and histological indices.
Results
In a first part, 78 patients with sAH were matched on bilirubin levels with 23 patients with DC. Lipidomics identified a distinct sAH signature involving glycerophospholipids, including PC(34:2) (OR 2.18, 95%CI:1.45-7.05, p=0.01), PC(O-38:5) (OR 3.31, 95%CI:2.23-7.14, p=0.002), PI(38:4) (OR 0.71, 95%CI:0.46-0.88, p=0.02), and LPC(18:1) (OR 0.47, 95%CI:0.32-0.82, p=0.01). These lipids demonstrated excellent discriminatory power between sAH and DC with areas under the receiver operating characteristic curve (AUROCs) between 0.87 and 0.88. In a second part, in 159 sAH patients, specific lipids including carnitines CAR(2:0) (OR 2.51, 95%CI:1.25-4.96, p=0.008) and CAR(16:1) (OR 2.21, 95%CI:1.09-7.48, p=0.009), were linked to 90-day mortality. Acylcarnitines correlated with disease severity parameters such as MELD, pro-inflammatory cytokines levels, and hepatocyte ballooning on pathology.
Conclusion
Untargeted lipidomics identified a glycerophospholipid and sphingolipid signature distinguishing sAH from DC, implicating lipid species involved in liver regeneration and immune function. Acylcarnitine accumulation in sAH patients with poor prognosis suggests mitochondrial dysfunction and warrants further investigation into therapeutic potential.
Severe alcohol-related hepatitis (sAH) is an inflammatory condition with high short-term mortality. Hypothesis-driven approaches have failed to identify effective treatments. Given the role of lipids as inflammatory mediators, this study aimed to identify lipidomic changes and lipid species associated with sAH and mortality risk.
Method
Untargeted lipidomics was performed on serum samples from two cohorts of patients with sAH and decompensated cirrhosis (DC). Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess lipidome changes. Correlations were made with lipoproteins, lipid mediators, cytokines, cytokeratin fragments, and histological indices.
Results
In a first part, 78 patients with sAH were matched on bilirubin levels with 23 patients with DC. Lipidomics identified a distinct sAH signature involving glycerophospholipids, including PC(34:2) (OR 2.18, 95%CI:1.45-7.05, p=0.01), PC(O-38:5) (OR 3.31, 95%CI:2.23-7.14, p=0.002), PI(38:4) (OR 0.71, 95%CI:0.46-0.88, p=0.02), and LPC(18:1) (OR 0.47, 95%CI:0.32-0.82, p=0.01). These lipids demonstrated excellent discriminatory power between sAH and DC with areas under the receiver operating characteristic curve (AUROCs) between 0.87 and 0.88. In a second part, in 159 sAH patients, specific lipids including carnitines CAR(2:0) (OR 2.51, 95%CI:1.25-4.96, p=0.008) and CAR(16:1) (OR 2.21, 95%CI:1.09-7.48, p=0.009), were linked to 90-day mortality. Acylcarnitines correlated with disease severity parameters such as MELD, pro-inflammatory cytokines levels, and hepatocyte ballooning on pathology.
Conclusion
Untargeted lipidomics identified a glycerophospholipid and sphingolipid signature distinguishing sAH from DC, implicating lipid species involved in liver regeneration and immune function. Acylcarnitine accumulation in sAH patients with poor prognosis suggests mitochondrial dysfunction and warrants further investigation into therapeutic potential.
Date Issued
2025-06-01
Date Acceptance
2025-02-17
Citation
JHEP Reports, 2025, 7 (6), pp.10136-10136
ISSN
2589-5559
Publisher
Elsevier
Start Page
10136
End Page
10136
Journal / Book Title
JHEP Reports
Volume
7
Issue
6
Copyright Statement
© 2025 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
License URL
Identifier
10.1016/j.jhepr.2025.101367
Publication Status
Published
Article Number
101367
Date Publish Online
2025-03-01