ArticleClinical and molecular hepatology2025
Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure.
Article in Clinical and molecular hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Endogenous phosphatidylcholine 16:0/20:4 increases to promote liver regeneration in hepatectomy.iScience · 2026Article
- Methodological considerations for lipidomic and fungal peptide-based risk stratification in acute liver failure: Letter to the editor on "Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure".Clinical and molecular hepatology · 2026Article
- Impaired fungal surveillance with Kennedy pathway activation drives acute liver failure, validated in preclinical models: Correspondence to letter to the editor on "Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure".Clinical and molecular hepatology · 2026Article
- Distinct bile mycobiome signature identifies fungal peptide panel predictive for gallbladder carcinoma.Molecular therapy. Oncology · 2026Article
- Acute-on-chronic liver failure: pathophysiological mechanisms and clinical management.Nature reviews. Gastroenterology & hepatology · 2026Review
- Lipidomic profiles associated with treatment related hepatotoxicity in children with acute lymphoblastic leukemia.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- Plasma lipidomic and fungal signatures predict early mortality in acute liver failure.Clinical and molecular hepatology · 2026Article
- Metabolomic profiling of Ashwagandha (Withania somnifera): linking bioactive compounds to functional therapeutic roles.Frontiers in molecular biosciences · 2026Article
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17 authors.
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Abstract
BACKGROUND/
aimsAcute liver failure (ALF) has high mortality predominantly due to compromised immune system and increased vulnerability to bacterial and fungal infections.
methodsPlasma lipidome and fungal peptide-based community (mycobiome) analysis were performed in discovery cohort (ALF=40, healthy=5) and validated in a validation cohort of 230 patients with ALF using high-resolution-mass-spectrometry, artificial neural network (ANN) and machine learning (ML).
resultsUntargeted lipidomics identified 2,013 lipids across 8 lipid group. 5 lipid-species-phosphatidylcholine (PC)[15:0/17:0], PC[20:1/14:1], PC[26:4/10:0], PC[32:0] and TG[4:0/10:0/23:6]-significantly differentiated ALF-NS (FC>10, P<0.05, FDR<0.01). Mycobiome alpha/beta diversity was significantly higher and showed 4 phyla and >20 species significantly dysregulated in ALF-NS linked with lipid metabolism, fatty acid elongation in ER, and others (P<0.05). Lipid and mycobiome diversity values in ALF-NS were strongly correlated (r2>0.7, P<0.05). Multi-modular correlation network showed striking associations between lipid, fungal peptide modules, and clinical parameters specific to ALF-NS (P<0.05). Cryptococcus amylolentus CBS6039 and Penicillium oxalicum 1142 directly correlated with phosphatidylcholine, triglycerides, and severity in ALF-NS (r2>0.85, P<0.05). POD-fungus and POD-lipids showed direct association with infection, necrosis, and hepatic encephalopathy (Beta>1.2, P<0.05). POD-lipid (AUC=0.969 and HR=1.99 [1.02-2.04]) superseded POD-fungus and severity indices for early-mortality prediction. Finally, significant increase in PC (15:0/17:0) level showed highest normalized importance, and ANNs and ML predicted early mortality with >95% accuracy, sensitivity, and specificity. Interestingly, fungal surveillance protein Clec7a was significantly downregulated (>2-fold), leading to a notable increase in fungal infection-mediated choline/phosphatidylcholine and associated enzymes (FC>1.5; Kennedy cycle). This contributed to phosphatidic acid-mediated hyper-inflammation in ALF-NS.
conclusionIn ALF, the plasma lipidome and mycobiome are dysregulated. Increased circulating phosphatidylcholine could stratify ALF predisposed to early mortality or require emergency liver transplantation.
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