{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:53:41Z","timestamp":1791262421330,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Definitions of acute-on-chronic liver failure (ACLF) differ, with a focus on extrahepatic organ failures on the basis of previously compensated or decompensated cirrhosis in EASL-CLIF-ACLF versus hepatic failure in patients without previous decompensation in APASL-ACLF. Here, we explored whether patterns of systemic inflammation and immune cell alterations differ between these types of ACLF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Consecutive patients with acute decompensation, EASL-CLIF- or APASL-ACLF were recruited from two liver centres. Patterns of systemic inflammation were characterized by Olink analysis and changes in circulating immune cells by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 374 patients with acute decompensation (AD) were identified, of whom 56 fulfilled exclusively the EASL-CLIF-definition of ACLF (15% of all patients), while only 19 patients (5.1% of all patients) met exclusively the APASL-definition. APASL-ACLF was associated with higher bilirubin, lower creatinine, higher INR and higher hemoglobin concentrations compared to EASL-ACLF. Patterns of systemic inflammation differed between EASL-CLIF and APASL-ACLF. For example, FGF-23, IL-17 or VEGF-A were associated with EASL-CLIF-ACLF, while FGF-19 or low IL-12 were associated with APASL-ACLF. Moreover, patients with EASL-CLIF-ACLF had significantly lower counts of CD8+ T cells, while in APASL-ACLF a reduction of CD4+ T cell was characteristic. Detailed immune cell phenotyping revealed distinct expression of co-stimulatory molecules, inhibitory molecules and T cell activation markers in APASL-ACLF compared to patients with AD or EASL-CLIF-ACLF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We provide preliminary evidence that EASL-CLIF- and APASL-ACLF are associated with different changes in systemic inflammation patterns and immune cell phenotypes, suggesting that both types of ACLF might be pathophysiologically different.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1893968","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:25:24Z","timestamp":1791260724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["APASL-ACLF without previous decompensation is immunologically distinct from EASL-CLIF-ACLF with previous decompensation"],"prefix":"10.3389","volume":"17","author":[{"given":"Mona-May","family":"Langer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]},{"name":"Department for Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Bauschen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Guckenbiehl","sequence":"additional","affiliation":[{"name":"Department for Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen","place":["Essen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"Denk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Stadler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, LMU University Hospital","place":["Munich, Germany"]},{"name":"Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz","place":["Mainz, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","article-title":"Further decompensation as a new prognostic stage in cirrhosis. 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