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@article{Artru:2025:10.1016/j.jhepr.2025.101367,
author = {Artru, F and Atkinson, S and Trovato, F and Tyson, LD and Patel, VC and Vergis, N and Kano, N and Goldin, R and Quaglia, A and Pechlivanis, A and Morgan, P and Mujib, S and Cavazza, A and Jerome, E and Zentar, M and Sheth, R and Morrison, M and Triantafyllou, E and Holmes, E and Gómez-Romero, M and McPhail, MJ and Thursz, M},
doi = {10.1016/j.jhepr.2025.101367},
journal = {JHEP Reports},
pages = {10136--10136},
title = {Lipidomics-based plasma signature of alcohol-related hepatitis linked to short-term mortality},
url = {http://dx.doi.org/10.1016/j.jhepr.2025.101367},
year = {2025}
}
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TY  - JOUR
AB  - IntroductionSevere 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.MethodUntargeted 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.ResultsIn 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.ConclusionUntargeted 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.
AU  - Artru,F
AU  - Atkinson,S
AU  - Trovato,F
AU  - Tyson,LD
AU  - Patel,VC
AU  - Vergis,N
AU  - Kano,N
AU  - Goldin,R
AU  - Quaglia,A
AU  - Pechlivanis,A
AU  - Morgan,P
AU  - Mujib,S
AU  - Cavazza,A
AU  - Jerome,E
AU  - Zentar,M
AU  - Sheth,R
AU  - Morrison,M
AU  - Triantafyllou,E
AU  - Holmes,E
AU  - Gómez-Romero,M
AU  - McPhail,MJ
AU  - Thursz,M
DO  - 10.1016/j.jhepr.2025.101367
EP  - 10136
PY  - 2025///
SN  - 2589-5559
SP  - 10136
TI  - Lipidomics-based plasma signature of alcohol-related hepatitis linked to short-term mortality
T2  - JHEP Reports
UR  - http://dx.doi.org/10.1016/j.jhepr.2025.101367
UR  - https://doi.org/10.1016/j.jhepr.2025.101367
ER  -
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