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Validation cohorts comprised 287 participants with severe alpha1\u2010antitrypsin deficiency (Pi*ZZ genotype), and 960 people living with HIV, who underwent liver stiffness measurement (LSM) via transient elastography. Selected proteomic parameters were compared to routine measurements. Bayes\u2010moderated linear models (covariates: age and sex) assessed the differential abundance. Logistic regression was used to develop and validate a prognostic score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Routine gamma\u2010glutamyltransferase (GGT) and aspartate aminotransferase (AST) strongly correlated with proteomic measurements (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.92 and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.71, respectively). Similarly, proteomic\u2010based thrombospondin\u20102 levels correlated with immunoassay\u2010based values (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.85). Twenty proteins were consistently associated with future MALOs\/increased liver stiffness in all cohorts. A novel five\u2010component proteomic score derived from the UK Biobank cohort demonstrated superior predictive power for MALOs (AUROC\u2009=\u20090.84) compared to AST\u2010to\u2010platelet\u2010ratio index (AUROC\u2009=\u20090.73) and Fibrosis\u20104 index (AUROC\u2009=\u20090.72), with stable performance in obese and diabetic subcohorts. In people living with HIV and alpha1\u2010antitrypsin deficiency patients, all five components increased across fibrosis stages and the proteomic score outperformed AST\u2010to\u2010platelet\u2010ratio\/Fibrosis\u20104 index in predicting significant LSM\u2010based liver fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identify a new proteomic score comprising epithelial\/hepatic stellate cell markers that yields a robust predictive performance across different liver disease aetiologies. Thereby, we demonstrate the usefulness of emerging proteomic techniques in hepatology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The registry study is listed at ClinicalTrials.gov (NCT02929940)<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70656","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:25:38Z","timestamp":1776403538000},"page":"74-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Affinity Proteomics\u2010Based Non\u2010Invasive Detection of Clinically Significant Liver Disease"],"prefix":"10.1111","volume":"64","author":[{"given":"Sriram","family":"Balasubramani","sequence":"first","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Remih","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"},{"name":"Department of Gastroenterology and Hepatology Medical University Lausitz\u2010Carl\u2010Thiem  Cottbus Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sophie","family":"Karl","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Alexandra","family":"Borchert","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Schrader","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-5705","authenticated-orcid":false,"given":"Malin","family":"Fromme","sequence":"additional","affiliation":[{"name":"Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Kayatekin","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Levit","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithra","family":"Krishnaswami","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise E.","family":"van Eekeren","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Centre  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. 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