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The aim of this study, which is a secondary analysis of the GRAFT study (NCT02669680), was to identify potential prognostic biomarkers in ACLF and to find markers that could be used to predict response to G-CSF treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Blood samples from 79 patients randomized in the GRAFT study to receive G-CSF (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200940) or standard medical therapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939) were collected at different timepoints. Samples were analyzed for cells, cytokines, extracellular particles, cell-free DNA, and functional properties. An exploratory approach was taken, whereby the measured variables were subjected to univariate and multivariate Cox analyses, and the patients were stratified into clusters by unsupervised hierarchical clustering.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with ACLF had increased plasma levels of pro-inflammatory cytokines and increased absolute levels of specific cell populations when compared to healthy controls. ROC curve analysis suggested that plasma VEGF-A levels at baseline (timepoint) are a prognostic factor of transplant-free survival (AUC: 0.70; 95%CI 0.56\u20130.84). Hierarchical clustering of circulating immune cell populations at baseline appeared to define a patient subset within the analyzed G-CSF-treated patients with improved median transplant-free survival (102\u00a0days vs 16\u00a0days;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). In our study, a higher percentage of CD39\n                      <jats:sup>+<\/jats:sup>\n                      lymphocytes serves as an independent predictor of unfavorable outcomes following G-CSF treatment (HR: 1.05, 95%CI: 1.01\u20131.09,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>VEGF-A appears to be a suitable biomarker for predicting the prognosis of patients with ACLF. With the help of hierarchical cell clusters, ACLF patients who could benefit from G-CSF therapy could be identified and selected prior to treatment. CD39 expression on lymphocytes seems suitable to allow stratification. Further testing and validation are necessary and could help to adapt treatment options for each individual patient.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-026-11069-5","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T06:46:35Z","timestamp":1772865995000},"page":"852-863","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune biomarkers predicting response to G-CSF in acute-on-chronic liver failure: results from a GRAFT trial sub-study"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1841-1495","authenticated-orcid":false,"given":"Katrin","family":"Splith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Berndt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp K.","family":"Haber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Wabitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Feldbr\u00fcgge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Herber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anett","family":"Schmiedeknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Mengwasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Bruns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Reuken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Goeser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Aehling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Galle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. 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CE is a shareholder of the UCL Spin-out Company Hepyx. CE is one of the named inventors on the patents surrounding the use of G-TAK in ACLF, which have been filed as a priority application. This patent has been licensed to Hepyx Ltd. TB: Receipt of honoraria or consultation fees or participation in a company sponsored speaker\u2019s bureau: Abbvie, Alexion, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MSD\/Merck, Novartis, and Sequana Medical. Receipt of grants\/research supports: Abbvie, SCR: Scientific founder of Purinomia Biotech Inc and consultant for eGenesis, AbbVie and Cyncado Therapuetics; SCR interests are reviewed and managed by Beth Israel Deaconess Medical Center following their conflict-of-interest policies. MS: Receipt of honoraria or consultation fees or participation in a company sponsored speaker\u2019s bureau: Merck Serono GmbH, Bayer AG, ERBE Elektromedizin GmbH, Amgen Inc., AstraZeneca, Avateramedical GmbH, Johnson & Johnson Medical GmbH, Takeda Pharmaceutical Limited, Olympus K.K., Medtronic GmbH, Intuitive Surgical Inc., Corzamedical, Baxter Int Inc. PAR received lecture and\/or consulting fees from Pfizer, Gilead, BMS, CSL Behring, CSL Vifor, and Advanz Pharma. All other authors declared no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the ethics committee and by the respective governmental competent authority (BfArM). The study protocol complies with the ethics guidelines of the 1975 Declaration of Helsinki as well as all pertinent national laws and the ICH guidelines for Good Clinical Practice (GCP) (June 1996) and CPMP\/ICH\/135\/95 (September 1997). All patients provided written informed consent. ClinicalTrails.gov number\u2014NCT02669680.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}