{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:23:59Z","timestamp":1782743039102,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["825510"],"award-info":[{"award-number":["825510"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["UEG Journal"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatohepatitis (MASH) increasingly drives hepatocellular carcinoma (HCC) development. We characterized inflammatory infiltrates in liver biopsies from MASH patients who developed HCC versus controls to identify predictive immune signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Formalin\u2010fixed paraffin\u2010embedded (FFPE) liver biopsies from MASH patients were categorized as pre\u2010HCC MASH (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010) or control MASH (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a013) by the ESCALON consortium. Standardized histological analysis and multiplexed immunohistochemistry were performed targeting CD4, CD8, PD1, PDL1, FoxP3, CXCR6, CD3, CD68, and CD20 using a PhenoImager Fusion scanner. Single\u2010cell RNA\u2010seq datasets characterized hepatic CD4 T cell heterogeneity. Clinical parameters measured included ALT, AST, GGT, alkaline phosphatase, platelets, and INR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pre\u2010HCC MASH showed inflammation extending from portal to periportal areas versus portal\u2010only distribution in controls. Analysis of 291,908 cells revealed significantly higher CD4+ density (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0243) and CD4+PD1+ cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017) in pre\u2010HCC patients, while CD8+ and regulatory T cell densities remained unchanged. Single\u2010cell RNA\u2010seq identified potential phenotypic shifts from Th1 cytotoxicity toward tissue\u2010repair and Th17 CD4+ T cells in MASH livers. Combined immunological and clinical variables (sex, age, CD4+ T cell numbers, ALT, alkaline phosphatase and platelets) achieved excellent predictive performance (ROC\u2010AUC\u00a0=\u00a00.944) for HCC development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increase in liver CD4+ T cell infiltration characterizes MASH\u2010to\u2010HCC progression. These immune signatures combined with clinical parameters demonstrate remarkable predictive value for identifying high\u2010risk MASH patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ueg2.70159","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:33:29Z","timestamp":1765586009000},"source":"Crossref","is-referenced-by-count":3,"title":["Hepatic CD4 T Cells Predict Hepatocellular Carcinoma Risk on Metabolic Dysfunction\u2010Associated Steatohepatitis Patients"],"prefix":"10.1002","volume":"14","author":[{"given":"Emilse","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Hospital Privado Centro M\u00e9dico de C\u00f3rdoba S.A.  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Simon","sequence":"additional","affiliation":[{"name":"Medizinische Hochschule Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Dhooge","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI\u2010CONICET) Facultad de Ciencias Qu\u00edmicas Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7681-9058","authenticated-orcid":false,"given":"Marina","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Hospital Privado Centro M\u00e9dico de C\u00f3rdoba S.A.  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