{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:58Z","timestamp":1785437038780,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["KA 5390\/2-1"],"award-info":[{"award-number":["KA 5390\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KA 5390\/2-1"],"award-info":[{"award-number":["KA 5390\/2-1"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Steatotic liver disease (SLD) is characterised by profound metabolic reprogramming, yet no single biomarker reliably distinguishes disease entities, stages or sex-specific risk profiles. By integrating serum metabolomic signatures as a liquid biopsy with tumour-associated CSC marker profiles in a sex-stratified analytical framework, we aimed to identify biologically meaningful differences and improve strategies for early, presymptomatic detection of SLD progression and HCC. The present study focuses on a targeted panel of 12 strongly dysregulated serum metabolites as candidate biomarkers of disease progression, quantified by NMR-based metabolomics and ELISA and complemented by CSC marker staining. We combined these NMR-based metabolomic \u2018liquid biopsy\u2019 data with circulating tumour-associated biomarkers, MELD-based risk assessment and tissue-level CSC marker expression across MetALD, MASLD, immune-mediated and cancerogenic liver disease, HCC and healthy controls. Female MetALD patients showed the second highest mortality after HCC, with lower survival than male cancer patients, despite MELD 3.0 assigning ~50% higher scores in women. MetALD mortality clustered with GP73, CD44, metabolomics and AA\/3HB ratio, indicating a distinct, high-risk female phenotype. Integrating liquid-based metabolomic profiling, AA\/3HB redox assessment, CSC markers and MELD 3.0 into sex-sensitive diagnostic pathways may improve early detection and risk stratification of alcohol-associated SLD, especially in women.<\/jats:p>","DOI":"10.3390\/ijms27114695","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"4695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomics-Enhanced Liquid Biopsy Identifies Early Heptocellular Injury in Females with MetALD"],"prefix":"10.3390","volume":"27","author":[{"given":"Anika","family":"Volkmar","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"},{"name":"Center for Translational Medicine, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4030-7431","authenticated-orcid":false,"given":"Gregor","family":"Mattert","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"},{"name":"Center for Translational Medicine, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Deisinger","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Brandenburg an der Havel, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelius","family":"Schulze","sequence":"additional","affiliation":[{"name":"I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5542-579X","authenticated-orcid":false,"given":"Asmus","family":"Heumann","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-3769","authenticated-orcid":false,"given":"Werner","family":"Dammermann","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"},{"name":"Center for Translational Medicine, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany"},{"name":"Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6074-5268","authenticated-orcid":false,"given":"Selina","family":"Strathmeyer","sequence":"additional","affiliation":[{"name":"Lifespin GmbH, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-8774","authenticated-orcid":false,"given":"Steffen","family":"Heelemann","sequence":"additional","affiliation":[{"name":"Lifespin GmbH, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kalinski","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospital Brandenburg an der Havel, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"L\u00fcth","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"},{"name":"Center for Translational Medicine, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany"},{"name":"Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-1724","authenticated-orcid":false,"given":"Janine","family":"Kah","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"},{"name":"Center for Translational Medicine, Brandenburg Medical School Theodor Fontane, 14770 Brandenburg an der Havel, Germany"},{"name":"I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"},{"name":"Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg, 14770 Brandenburg an der Havel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jhep.2022.08.021","article-title":"Global burden of primary liver cancer in 2020 and predictions to 2040","volume":"77","author":"Rumgay","year":"2022","journal-title":"J. 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