{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:55:39Z","timestamp":1790916939170,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"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<\/jats:title>\n                    <jats:p>Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality. Valid prognostic biomarkers are required to refine risk stratification and improve clinical management. This study aimed to identify potential prognostic biomarkers for predicting clinical outcomes in ACLF patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-four ACLF patients admitted to the Affiliated Hospital of Southwest Medical University between January 2021 and April 2022 were enrolled for retrospective analysis of baseline characteristics, clinical parameters and clinical outcomes. Forty patients were randomly selected for data-independent acquisition mass spectrometry (DIA-MS)-based proteomic profiling and differential protein analysis, and categorized into survival (n = 20) and non-survival (n = 20) groups according to 90-day outcomes. Bioinformatics analyses were performed to characterize candidate targets. Apolipoprotein C1 (APOC1) levels were validated by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic performance and compare it with a newly established model, conventional biomarkers and existing scoring systems. Single-cell RNA sequencing was applied to determine the cellular source and distribution of APOC1, and molecular docking was performed to screen potential APOC1-targeted therapeutic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomic analysis identified 41 differentially expressed proteins (DEPs). Protein\u2013protein interaction network analysis revealed that APOC1 occupied a core hub position in the network. Functional enrichment analysis indicated that DEPs were mainly involved in lipid metabolism, lipoprotein clearance and cholesterol efflux. ELISA confirmed significantly higher plasma APOC1 levels in the survival group, suggesting a protective role. Comparative ROC analysis demonstrated favorable prognostic performance of APOC1. Incorporation of APOC1 into traditional scoring systems moderately improved predictive efficacy. Single-cell RNA sequencing further revealed that APOC1 was predominantly expressed in hepatic macrophages. Molecular docking showed strong binding affinities of APOC1 with saikosaponin D and resveratrol, with binding energies of \u22127.8 and \u22126.7 kcal\/mol, respectively. Elevated plasma APOC1 was positively correlated with survival in ACLF patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Plasma APOC1 serves as a novel prognostic biomarker for ACLF. Integrating APOC1 into conventional scoring systems yields complementary prognostic value. Hepatic macrophages represent the primary cellular source of APOC1, and saikosaponin D and resveratrol are promising candidate agents targeting APOC1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1881095","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:41:20Z","timestamp":1790916080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic value of APOC1 in patients with acute-on-chronic liver failure"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongyan","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianyu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjian","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglian","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.015","article-title":"The global burden of liver disease","volume":"21","author":"Younossi","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.04.021","article-title":"Easl clinical practice guidelines on acute-on-chronic liver failure","volume":"79","year":"2023","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-025-01159-4","article-title":"Acute-on-chronic liver failure: Pathophysiological mechanisms and clinical management","volume":"25","author":"Sarin","year":"2026","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100807","article-title":"Roles of systemic inflammatory and metabolic responses in the pathophysiology of acute-on-chronic liver failure","volume":"5","author":"Cl\u00e0ria","year":"2023","journal-title":"JHEP Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/hc9.0000000000000917","article-title":"Acute-on-chronic liver failure and immune dysregulation: Systemic inflammation and immunoparesis paradox","volume":"10","author":"Drago","year":"2026","journal-title":"Hepatol Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.14218\/jcth.2021.00055","article-title":"Cytokine storm of Covid-19 and its impact on patients with and without chronic liver disease","volume":"9","author":"Premkumar","year":"2021","journal-title":"J Clin Transl Hepatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15733","article-title":"Mechanisms and treatment approaches for aclf","volume":"45","author":"Piano","year":"2025","journal-title":"Liver Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/he.2000.5852","article-title":"A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts","volume":"31","author":"Malinchoc","year":"2000","journal-title":"Hepatology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.02.010","article-title":"Evidence-based incorporation of serum sodium concentration into meld","volume":"130","author":"Biggins","year":"2006","journal-title":"Gastroenterology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.05.026","article-title":"Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure","volume":"75","author":"Li","year":"2021","journal-title":"J Hepatol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1053\/j.gastro.2021.08.050","article-title":"Meld 3.0: The model for end-stage liver disease updated for the modern era","volume":"161","author":"Kim","year":"2021","journal-title":"Gastroenterology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/1849454418777186","article-title":"Evolution of proteomic biomarker for chronic liver disease: Promise into reality","volume":"7","author":"Nallagangula","year":"2018","journal-title":"J Circ biomark"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100800","article-title":"Data-independent acquisition: A milestone and prospect in clinical mass spectrometry-based proteomics","volume":"23","author":"Fr\u00f6hlich","year":"2024","journal-title":"Mol Cell Proteomics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100712","article-title":"Acquisition and analysis of dia-based proteomic data: A comprehensive survey in 2023","volume":"23","author":"Lou","year":"2024","journal-title":"Mol Cell Proteomics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000565","article-title":"Acute liver failure: Biomarkers evaluated by the acute liver failure study group","volume":"14","author":"Rakela","year":"2023","journal-title":"Clin Transl Gastroenterol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"5939","DOI":"10.3390\/ijms20235939","article-title":"Apolipoprotein C1: Its pleiotropic effects in lipid metabolism and beyond","volume":"20","author":"Fuior","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1186\/s12967-023-04294-1","article-title":"Intrahepatic macrophage reprogramming associated with lipid metabolism in hepatitis B virus-related acute-on-chronic liver failure","volume":"21","author":"Peng","year":"2023","journal-title":"J Transl Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1038\/s41467-019-11004-3","article-title":"Defective Hnf4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis","volume":"10","author":"Argemi","year":"2019","journal-title":"Nat Commun."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1287072","article-title":"Data independent acquisition reveals in-depth serum proteome changes in uremic pruritus","volume":"15","author":"Wen-Jing","year":"2024","journal-title":"Front Physiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2147\/idr.S417472","article-title":"Bikunin: A promising prognostic biomarker for acute-on-chronic liver failure in patients with viral hepatitis B","volume":"16","author":"Qin","year":"2023","journal-title":"Infect Drug Resist"},{"key":"B22","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1186\/s12859-018-2486-6","article-title":"Idep: An integrated web application for differential expression and pathway analysis of rna-seq data","volume":"19","author":"Ge","year":"2018","journal-title":"BMC Bioinf"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8","article-title":"Finngen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1631-3","article-title":"Resolving the fibrotic niche of human liver cirrhosis at single-cell level","volume":"575","author":"Ramachandran","year":"2019","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.042","article-title":"Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis","volume":"144","author":"Moreau","year":"2013","journal-title":"Gastroenterology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1583202","article-title":"Acute-on-chronic liver failure: Definition, diagnosis, and clinical characteristics","volume":"36","author":"Arroyo","year":"2016","journal-title":"Semin Liver Dis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.14218\/jcth.2024.00203","article-title":"Metabolic dysregulation and metabolite imbalances in acute-on-chronic liver failure: Impact on immune status","volume":"12","author":"Zhang","year":"2024","journal-title":"J Clin Transl Hepatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-333308","article-title":"Single-cell multimodal analysis reveals the dynamic immunopathogenesis of hbv-aclf progression","volume":"75","author":"Liang","year":"2026","journal-title":"Gut"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2018-101103","article-title":"Acute-on-chronic liver failure: Definition, prognosis and management","volume":"11","author":"Amin","year":"2020","journal-title":"Frontline Gastroenterol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.657631","article-title":"Identification of a potential mirna-mrna regulatory network associated with the prognosis of hbv-aclf","volume":"8","author":"Ma","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.011","article-title":"Metabolic biomarkers significantly enhance the prediction of hbv-related aclf occurrence and outcomes","volume":"79","author":"Zhang","year":"2023","journal-title":"J Hepatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.5009\/gnl220449","article-title":"Single-cell rna sequencing shows t-cell exhaustion landscape in the peripheral blood of patients with hepatitis B virus-associated acute-on-chronic liver failure","volume":"18","author":"Yao","year":"2024","journal-title":"Gut Liver"},{"key":"B34","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.7150\/thno.31991","article-title":"Circulating proteomic panels for diagnosis and risk stratification of acute-on-chronic liver failure in patients with viral hepatitis B","volume":"9","author":"Sun","year":"2019","journal-title":"Theranostics"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae079","article-title":"Plasma mertk is a promising biomarker for the diagnosis and prognosis of hepatitis B virus-related acute-on-chronic liver failure","volume":"230","author":"Lu","year":"2024","journal-title":"J Infect Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000041503","article-title":"Apoc3 as a potential prognostic factor for hepatitis B virus-related acute-on-chronic liver failure","volume":"104","author":"Wang","year":"2025","journal-title":"Med (Baltimore)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2329-7","article-title":"Nanoparticle (np)-mediated apoc1 silencing to inhibit mapk\/erk and nf-Kb pathway and suppress breast cancer growth and metastasis","volume":"66","author":"Liu","year":"2023","journal-title":"Sci China Life Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323395","article-title":"Pbmc transcriptomics identifies immune-metabolism disorder during the development of hbv-aclf","volume":"71","author":"Li","year":"2022","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1186\/s12933-022-01703-5","article-title":"Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: A systematic review","volume":"21","author":"Rouland","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12559","article-title":"Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol-related acute-on-chronic liver failure","volume":"35","author":"Mehta","year":"2015","journal-title":"Liver Int"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.3390\/cells9122632","article-title":"Leukocytes, systemic inflammation and immunopathology in acute-on-chronic liver failure","volume":"9","author":"Casulleras","year":"2020","journal-title":"Cells"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02948","article-title":"The role of monocytes and macrophages in acute and acute-on-chronic liver failure","volume":"9","author":"Triantafyllou","year":"2018","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15644","article-title":"Mechanisms of immunity in acutely decompensated cirrhosis and acute-on-chronic liver failure","volume":"45","author":"Engelmann","year":"2025","journal-title":"Liver Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/jci130197","article-title":"Plasminogen as a prognostic biomarker for hbv-related acute-on-chronic liver failure","volume":"130","author":"Wu","year":"2020","journal-title":"J Clin Invest"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-019-09946-3","article-title":"Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the Study of the Liver (Apasl): An update","volume":"13","author":"Sarin","year":"2019","journal-title":"Hepatol Int"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1881095\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:41:24Z","timestamp":1790916084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1881095\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2026.1881095"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1881095","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]},"article-number":"1881095"}}