{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:00Z","timestamp":1791557580340,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease, yet accurate early detection remains challenging. A particular diagnostic obstacle is distinguishing MASLD from metabolic dysfunction and alcohol\u2010related liver disease (MetALD), currently defined using clinically informed moderate alcohol consumption thresholds without biological validation. This study aimed to identify and externally validate plasma proteomic signatures associated with MASLD and assess whether proteomic profiles support a molecular distinction between MASLD and MetALD as currently defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed plasma proteomic profiles using OLINK data from UK Biobank (UKB) participants with liver MRI. MASLD was defined as MRI\u2010PDFF \u2265\u20095% and metabolic dysfunction (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009165), MetALD (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200946) as MASLD with additional moderate alcohol intake and controls as PDFF &lt;\u20095% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009741).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to controls, participants with MASLD showed 17 upregulated and 3 downregulated proteins after Bonferroni correction (adjusted\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Among upregulated proteins, leptin (LEP), fatty acid\u2010binding protein, liver (FABP1) and aminoacylase1 (ACY1) and among downregulated, insulin\u2010like growth factor\u2010binding protein 1 (IGFBP1) were externally validated in an independent cohort (clinicaltrials.gov NCT02520609,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200947). Individuals with MetALD showed no significant proteomic distinction from MASLD. Although the small MetALD sample size may have limited detection of differences, direct differential expression analysis did not identify statistically significant differences between MASLD and MetALD under the current clinical thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MASLD was associated with a reproducible plasma proteomic signature enriched for proteins involved in lipid metabolism, inflammation and hormonal regulation. We did not identify a clear proteomic distinction between MASLD and MetALD under the current alcohol thresholds. However, this finding should be interpreted considering limited power and potential alcohol\u2010exposure misclassification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70873","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:45:31Z","timestamp":1790696731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct Plasma Proteomic Signatures Distinguish\n                    <scp>MASLD<\/scp>\n                    From Non\u2010Steatotic Individuals but Not From\n                    <scp>MetALD<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1358-496X","authenticated-orcid":false,"given":"Niharika","family":"Jakhar","sequence":"first","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9115-3228","authenticated-orcid":false,"given":"Tobias","family":"Seibel","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9783-097X","authenticated-orcid":false,"given":"Maria","family":"Mironova","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health  Bethesda Maryland USA"},{"name":"Division of Gastroenterology and Hepatology University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Mee\u00dfen","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Clusmann","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine Carl Gustav Carus TUD Dresden University of Technology  Dresden Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Dresden and German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Department of Medicine I Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9893-645X","authenticated-orcid":false,"given":"Yazhou","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9288-9826","authenticated-orcid":false,"given":"Thriveni B.","family":"Raju","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul\u2010Henry","family":"Koop","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care University Hospital RWTH Aachen  Aachen Germany"},{"name":"Else Kroener Fresenius Center for Digital Health, Faculty of Medicine Carl Gustav Carus TUD Dresden University of Technology  Dresden Germany"},{"name":"German Cancer Consortium (DKTK) Partner Site Dresden and German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Department of Medicine I Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8155-6534","authenticated-orcid":false,"given":"Juliette E.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Institute for Cell and Tumor Biology RWTH Aachen University, University Hospital Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-8697","authenticated-orcid":false,"given":"Ivan G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Institute for Computational Genomics University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-9197","authenticated-orcid":false,"given":"Thomas","family":"Stiehl","sequence":"additional","affiliation":[{"name":"Uniklinik RWTH Aachen, Institute for Computational Biomedicine &amp; Disease Modeling RWTH Aachen University  Aachen Germany"},{"name":"Department for Science and Environment Roskilde University  Roskilde Denmark"},{"name":"Center for Computational Life Sciences RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3783-6605","authenticated-orcid":false,"given":"Andreas","family":"Schuppert","sequence":"additional","affiliation":[{"name":"Center for Computational Life Sciences RWTH Aachen University  Aachen Germany"},{"name":"Institute for Computational Biomedicine, JRC for Computational Biomedicine RWTH Aachen University, University Hospital Aachen  Aachen 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