{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:55:08Z","timestamp":1793066108488,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome marked by rapid progression and high short-term mortality. In the Asia-Pacific region, where the hepatitis B virus (HBV) is endemic, HBV-related ACLF (HBV-ACLF) represents the most common subtype. The aim of this study was to develop and validate a concise and accurate nomogram for predicting 28-day mortality in patients with HBV-related ACLF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 159 patients with HBV-ACLF were enrolled, including 113 in the training cohort and 46 in the validation cohort. Clinical characteristics, routine laboratory parameters, and inflammatory cytokine levels were collected. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was applied to select variables, followed by multivariate logistic regression to construct a nomogram model (ICI). Model performance was evaluated in both cohorts using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA), and compared with COSSH-ACLF II, CLIF-C ACLF, AARC, CLIF-OFs, MELD, and CTP scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LASSO regression identified ln(INR), ln(Cr), ln(WBC), and ln(IL-6) as candidate predictors. Multivariate logistic regression further confirmed that ln(INR), ln(Cr), and ln(IL-6) were independent risk factors. The new model (ICI) demonstrated good discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.826 in the training cohort and 0.814 in the validation cohort. Calibration analysis showed excellent consistency, and decision curve analysis (DCA) indicated that the ICI model provided higher net clinical benefit across different threshold probabilities. Furthermore, compared with traditional models, the ICI model exhibited significant advantages in terms of discriminative ability and clinical benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The newly developed model (ICI) showed superior predictive performance for short-term prognosis in patients with HBV-ACLF, outperforming conventional scoring systems. It is anticipated that the ICI model will serve as a valuable instrument in complementing the conventional scoring system for the HBV-ACLF population in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1688479","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T05:38:43Z","timestamp":1768196323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of a short-term prognostic model for hepatitis B-related acute-on-chronic liver failure in a dual-center cohort"],"prefix":"10.3389","volume":"12","author":[{"given":"Huaidong","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruili","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanxi Bethune Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxue","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanxi Bethune Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongkuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12072-024-10773-4","article-title":"Acute-on-chronic liver failure (ACLF): the \u2018Kyoto consensus\u2019\u2014steps from Asia","volume":"19","author":"Choudhury","year":"2025","journal-title":"Hepatol Int"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"353","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"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1097\/HEP.0000000000000671","article-title":"AASLD practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis","volume":"79","author":"Karvellas","year":"2024","journal-title":"Hepatology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jhep.2023.04.021","article-title":"EASL clinical practice guidelines on acute-on-chronic liver failure","volume":"79","author":"Moreau","year":"2023","journal-title":"J Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"516","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":"ref6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41392-024-02072-z","article-title":"Liver diseases: epidemiology, causes, trends and predictions","volume":"10","author":"Gan","year":"2025","journal-title":"Sig Transduct Target Ther"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1136\/gutjnl-2020-322161","article-title":"Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis","volume":"71","author":"Mezzano","year":"2022","journal-title":"Gut"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.1002\/hep.30494","article-title":"Incidence and mortality of acute-on-chronic liver failure using two definitions in patients with compensated cirrhosis","volume":"69","author":"Mahmud","year":"2019","journal-title":"Hepatology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1093\/aje\/kwy083","article-title":"Acute-on-chronic liver failure in China: rationale for developing a patient registry and baseline characteristics","volume":"187","author":"Gu","year":"2018","journal-title":"Am J Epidemiol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1056\/NEJMra031087","article-title":"Hepatitis B virus infection--natural history and clinical consequences","volume":"350","author":"Ganem","year":"2004","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"7295","DOI":"10.2147\/JIR.S336626","article-title":"HMGB1-induced hepatocyte Pyroptosis expanding inflammatory responses contributes to the pathogenesis of acute-on-chronic liver failure (ACLF)","volume":"14","author":"Hou","year":"2021","journal-title":"JIR"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fimmu.2020.02013","article-title":"Abnormal innate immunity in acute-on-chronic liver failure: immunotargets for therapeutics","volume":"11","author":"Khanam","year":"2020","journal-title":"Front Immunol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jhep.2024.06.016","article-title":"Inflammasomes in chronic liver disease: hepatic injury, fibrosis progression and systemic inflammation","volume":"81","author":"Taru","year":"2024","journal-title":"J Hepatol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1053\/jhep.2001.22172","article-title":"A model to predict survival in patients with end\u2013stage liver disease","volume":"33","author":"Kamath","year":"2001","journal-title":"Hepatology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/bjs.1800600817","article-title":"Transection of the oesophagus for bleeding oesophageal varices","volume":"60","author":"Pugh","year":"1973","journal-title":"Br J Surg"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.jhep.2014.06.012","article-title":"Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure","volume":"61","author":"Jalan","year":"2014","journal-title":"J Hepatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1136\/gutjnl-2016-312670","article-title":"Acute-on-chronic liver failure: an update","volume":"66","author":"Hernaez","year":"2017","journal-title":"Gut"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1104","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":"ref19","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1136\/gutjnl-2017-314641","article-title":"Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-on-chronic liver failure","volume":"67","author":"Wu","year":"2018","journal-title":"Gut"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment and of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"37425213","DOI":"10.1016\/j.jhepr.2023.100848","article-title":"Transcriptomics unveils immune metabolic disruption and a novel biomarker of mortality in patients with HBV-related acute-on-chronic liver failure","volume":"5","author":"Liang","year":"2023","journal-title":"JHEP Rep"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.ajt.2024.06.021","article-title":"Common definitions and variables are needed for the United States to join the conversation on acute-on-chronic liver failure","volume":"24","author":"Ge","year":"2024","journal-title":"Am J Transplant"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.jhep.2024.03.036","article-title":"Acute-on-chronic liver failure \u2013 steps towards harmonization of the definition!","volume":"81","author":"Kulkarni","year":"2024","journal-title":"J Hepatol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1053\/jlts.2002.31340","article-title":"Model for end-stage liver disease and child-Turcotte-Pugh score as predictors of pretransplantation disease severity, posttransplantation outcome, and resource utilization in united network for organ sharing status 2A patients","volume":"8","author":"Brown","year":"2002","journal-title":"Liver Transpl"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e9857","DOI":"10.7717\/peerj.9857","article-title":"Assessing the prognostic scores for the prediction of the mortality of patients with acute-on-chronic liver failure: a retrospective study","volume":"8","author":"Zhang","year":"2020","journal-title":"PeerJ"},{"key":"ref26","first-page":"100638","article-title":"Predicting the survival benefit of liver transplantation in HBV-related acute-on-chronic liver failure: an observational cohort study","volume-title":"Lancet Reg Health West Pac","author":"Li","year":"2022"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/5091275","article-title":"The mechanisms of systemic inflammatory and immunosuppressive acute-on-chronic liver failure and application Prospect of single-cell sequencing","volume":"2022","author":"Kou","year":"2022","journal-title":"J Immunol Res"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13799","article-title":"Systemic inflammatory response syndrome in acute-on-chronic liver failure: relevance of \u2018golden window\u2019: a prospective study","volume":"32","author":"Choudhury","year":"","journal-title":"J Gastroenterol Hepatol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1027152","DOI":"10.1155\/2018\/1027152","article-title":"Systemic inflammation and acute-on-chronic liver failure: too much, not enough","volume":"2018","author":"Laleman","year":"2018","journal-title":"Can J Gastroenterol Hepatol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1016\/j.jhep.2015.07.004","article-title":"Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis","volume":"63","author":"Bernardi","year":"2015","journal-title":"J Hepatol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"32341","DOI":"10.1038\/srep32341","article-title":"Characterization of inflammatory response in acute-on-chronic liver failure and relationship with prognosis","volume":"6","author":"Sol\u00e9","year":"2016","journal-title":"Sci Rep"},{"key":"ref32","first-page":"21","article-title":"Role of immune dysfunction in acute-on-chronic liver failure: from pathogenesis to clinical prognosis","volume":"31","author":"Huang","year":"2021","journal-title":"Discovery Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.3748\/wjg.v26.i30.4479","article-title":"High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure","volume":"26","author":"Zhou","year":"2020","journal-title":"World J Gastroenterol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"22191","DOI":"10.1038\/s41598-025-06472-1","article-title":"Golgi protein 73 and IL-6 as strong predictors of short-term prognosis in patients with HBV-ACLF","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci Rep"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fimmu.2023.1133656","article-title":"Serum cytokine and chemokine profiles and disease prognosis in hepatitis B virus-related acute-on-chronic liver failure","volume":"14","author":"Zhu","year":"2023","journal-title":"Front Immunol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/978-1-4612-3210-0_14","article-title":"Interleukin-6","author":"Hirano","year":"1991","journal-title":"Peptide Growth Factors Their Receptors I"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"109130","DOI":"10.1016\/j.intimp.2022.109130","article-title":"Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach","volume":"111","author":"Aliyu","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"856587","DOI":"10.3389\/fimmu.2022.856587","article-title":"Bioenergetic failure drives functional exhaustion of monocytes in acute-on-chronic liver failure","volume":"13","author":"Maheshwari","year":"2022","journal-title":"Front Immunol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/s1074-7613(00)80334-9","article-title":"Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment","volume":"6","author":"Romano","year":"1997","journal-title":"Immunity"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"115403","DOI":"10.1016\/j.celrep.2025.115403","article-title":"The pro-inflammatory cytokine IL6 suppresses mitochondrial function via the gp130-JAK1\/STAT1\/3-HIF1\u03b1\/ERR\u03b1 axis","volume":"44","author":"Xu","year":"2025","journal-title":"Cell Rep"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1470488","DOI":"10.3389\/fimmu.2025.1470488","article-title":"Update on tocilizumab in rheumatoid arthritis: a narrative review","volume":"16","author":"Parisi","year":"2025","journal-title":"Front Immunol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"825749","DOI":"10.3389\/fphar.2022.825749","article-title":"Tocilizumab and COVID-19: timing of administration and efficacy","volume":"13","author":"Abidi","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41584-020-0419-z","article-title":"Translating IL-6 biology into effective treatments","volume":"16","author":"Choy","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.jhep.2024.03.031","article-title":"Acute kidney injury in patients with cirrhosis: acute disease quality initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting","volume":"81","author":"Nadim","year":"2024","journal-title":"J Hepatol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"396","DOI":"10.14218\/JCTH.2018.00035","article-title":"Acute kidney injury at admission is a better predictor of mortality than its persistence at 48 h in patients with acute-on-chronic liver failure","volume":"6","author":"Khatua","year":"2018","journal-title":"J Clin Transl Hepatol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1688479\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:01:05Z","timestamp":1774533665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1688479\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":45,"alternative-id":["10.3389\/fmed.2025.1688479"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1688479","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"article-number":"1688479"}}