IL-1 Receptor Antagonist as a Diagnostic Biomarker for Bacterial Infections in Acute Decompensation of Cirrhosis

IL-1 Receptor Antagonist as a Diagnostic Biomarker for Bacterial Infections in Acute Decompensation of Cirrhosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article IL-1 Receptor Antagonist as a Diagnostic Biomarker for Bacterial Infections in Acute Decompensation of Cirrhosis Georgios Konstantis, Andreas Schütte, Bjorn Jung, Moritz Passenberg, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7234753/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Background: Liver cirrhosis is a chronically progressive disease often leading to severe complications such as acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Both conditions are frequently triggered by bacterial infections. However, conventional biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP) have limited diagnostic accuracy for detecting infections in patients with cirrhosis. The aim of this study was to better characterize the inflammatory response in AD and ACLF and to identify reliable biomarkers for the early detection of bacterial infections. Methods: In this prospective study, 74 consecutive patients with liver cirrhosis and either AD or ACLF were enrolled between October 2022 and October 2023 during hospitalization at the University Hospital Essen. Bacterial infection was identified as a precipitating event in 33 patients, whereas other causes were found in the remaining 41 patients. In addition to CRP and PCT, several proinflammatory cytokines and interleukin receptor antagonists were analyzed, including IL-1β, IL-1RA, IL-17E, IL-17F, IL-17A, IL-6 and IL-23, which play central roles in type I and type III immune responses. Univariable logistic regression analyses were conducted to identify biomarkers significantly associated with bacterial infections. Significant biomarkers were then incorporated into multivariable models alongside predefined clinical parameters. Model performance and generalizability were evaluated through internal validation using 1,000-fold bootstrap resampling with 74 patients per sample. Results: Key biomarkers identified included CRP, PCT, IL-1β, and particularly IL-1RA. After dichotomization, the following combinations achieved the highest diagnostic accuracy for bacterial infection: IL-1RA alone (AUC: 0.762; 95% confidence interval [CI]: 0.652–0.872), IL-1RA combined with PCT (AUC: 0.750; 95% CI: 0.635–0.866), and IL-1RA combined with CRP (AUC: 0.744; 95% CI: 0.625–0.863). To minimize overfitting and improve model calibration, ridge regression was applied. The final model, which included IL-1RA and selected clinical parameters, achieved an AUC of 0.764 (95% CI: 0.654–0.874), with an accuracy of 73%, sensitivity of 61%, specificity of 83%, and precision of 74%. Based on this model, a risk stratification tool was developed that defined thresholds to achieve 80% sensitivity and specificity, respectively. A freely available online application was created to facilitate clinical implementation. Conclusion: In summary, the model developed in this study enables improved identification of bacterial infections in patients with liver cirrhosis. This could support earlier and more targeted therapy in this highly vulnerable high-risk population. External validation and application in larger cohorts are necessary to further confirm the clinical utility of the model. Health sciences/Biomarkers Health sciences/Diseases Health sciences/Gastroenterology Biological sciences/Immunology Health sciences/Medical research Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 07 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 15 Oct, 2025 Reviews received at journal 29 Sep, 2025 Reviewers agreed at journal 08 Sep, 2025 Reviews received at journal 04 Sep, 2025 Reviewers agreed at journal 02 Sep, 2025 Reviewers agreed at journal 14 Aug, 2025 Reviewers invited by journal 07 Aug, 2025 Editor assigned by journal 06 Aug, 2025 Editor invited by journal 06 Aug, 2025 Submission checks completed at journal 01 Aug, 2025 First submitted to journal 01 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7234753","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":497709579,"identity":"d781f8d8-f296-4d17-8728-cd50b46cba84","order_by":0,"name":"Georgios Konstantis","email":"data:image/png;base64,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","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":true,"prefix":"","firstName":"Georgios","middleName":"","lastName":"Konstantis","suffix":""},{"id":497709580,"identity":"3c45ea90-78df-4c2a-a1af-a414338d8364","order_by":1,"name":"Andreas Schütte","email":"","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Schütte","suffix":""},{"id":497709581,"identity":"875bf1e5-f18f-4b46-a594-caec57e41911","order_by":2,"name":"Bjorn Jung","email":"","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Bjorn","middleName":"","lastName":"Jung","suffix":""},{"id":497709582,"identity":"ebce80a1-c3e1-4b75-80cf-8b8aeb8027ff","order_by":3,"name":"Moritz Passenberg","email":"","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Moritz","middleName":"","lastName":"Passenberg","suffix":""},{"id":497709583,"identity":"e65747a3-ff14-4ec1-956e-445f3168d9d7","order_by":4,"name":"Lucie Jacquet","email":"","orcid":"","institution":"University Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Lucie","middleName":"","lastName":"Jacquet","suffix":""},{"id":497709584,"identity":"91f7436f-f78f-44ae-b273-bd0f319b202e","order_by":5,"name":"Clara Guntlisbergen","email":"","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Clara","middleName":"","lastName":"Guntlisbergen","suffix":""},{"id":497709585,"identity":"a144dd46-1572-4130-8d19-dda069b392cd","order_by":6,"name":"Nargiz Nuruzade","email":"","orcid":"","institution":"University of Duisburg-Essen","correspondingAuthor":false,"prefix":"","firstName":"Nargiz","middleName":"","lastName":"Nuruzade","suffix":""},{"id":497709586,"identity":"3748e1c8-e713-4680-917b-140a415b61bf","order_by":7,"name":"Dieter P. 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Both conditions are frequently triggered by bacterial infections. However, conventional biomarkers such as procalcitonin (PCT) and C-reactive protein (CRP) have limited diagnostic accuracy for detecting infections in patients with cirrhosis. The aim of this study was to better characterize the inflammatory response in AD and ACLF and to identify reliable biomarkers for the early detection of bacterial infections.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eIn this prospective study, 74 consecutive patients with liver cirrhosis and either AD or ACLF were enrolled between October 2022 and October 2023 during hospitalization at the University Hospital Essen. Bacterial infection was identified as a precipitating event in 33 patients, whereas other causes were found in the remaining 41 patients. In addition to CRP and PCT, several proinflammatory cytokines and interleukin receptor antagonists were analyzed, including IL-1β, IL-1RA, IL-17E, IL-17F, IL-17A, IL-6 and IL-23, which play central roles in type I and type III immune responses. Univariable logistic regression analyses were conducted to identify biomarkers significantly associated with bacterial infections. Significant biomarkers were then incorporated into multivariable models alongside predefined clinical parameters. Model performance and generalizability were evaluated through internal validation using 1,000-fold bootstrap resampling with 74 patients per sample.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eKey biomarkers identified included CRP, PCT, IL-1β, and particularly IL-1RA. After dichotomization, the following combinations achieved the highest diagnostic accuracy for bacterial infection: IL-1RA alone (AUC: 0.762; 95% confidence interval [CI]: 0.652\u0026ndash;0.872), IL-1RA combined with PCT (AUC: 0.750; 95% CI: 0.635\u0026ndash;0.866), and IL-1RA combined with CRP (AUC: 0.744; 95% CI: 0.625\u0026ndash;0.863). To minimize overfitting and improve model calibration, ridge regression was applied. The final model, which included IL-1RA and selected clinical parameters, achieved an AUC of 0.764 (95% CI: 0.654\u0026ndash;0.874), with an accuracy of 73%, sensitivity of 61%, specificity of 83%, and precision of 74%. Based on this model, a risk stratification tool was developed that defined thresholds to achieve 80% sensitivity and specificity, respectively. A freely available online application was created to facilitate clinical implementation.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eIn summary, the model developed in this study enables improved identification of bacterial infections in patients with liver cirrhosis. This could support earlier and more targeted therapy in this highly vulnerable high-risk population. External validation and application in larger cohorts are necessary to further confirm the clinical utility of the model.\u003c/p\u003e","manuscriptTitle":"IL-1 Receptor Antagonist as a Diagnostic Biomarker for Bacterial Infections in Acute Decompensation of Cirrhosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-12 13:35:45","doi":"10.21203/rs.3.rs-7234753/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-15T09:51:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T10:48:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212217843078309558543917515431508252993","date":"2025-09-08T10:51:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-04T17:12:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"223992803114945250744887787098917659171","date":"2025-09-02T13:39:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195871001243481213331262882903013154769","date":"2025-08-14T08:05:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-07T07:51:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-06T06:58:36+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-06T06:16:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-01T13:59:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-01T13:55:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"82e6e61b-9a4b-40e4-9161-ddefcb399646","owner":[],"postedDate":"August 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":52874447,"name":"Health sciences/Biomarkers"},{"id":52874448,"name":"Health sciences/Diseases"},{"id":52874449,"name":"Health sciences/Gastroenterology"},{"id":52874450,"name":"Biological sciences/Immunology"},{"id":52874451,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-12-08T16:04:04+00:00","versionOfRecord":{"articleIdentity":"rs-7234753","link":"https://doi.org/10.1038/s41598-025-30647-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-07 15:58:17","publishedOnDateReadable":"December 7th, 2025"},"versionCreatedAt":"2025-08-12 13:35:45","video":"","vorDoi":"10.1038/s41598-025-30647-5","vorDoiUrl":"https://doi.org/10.1038/s41598-025-30647-5","workflowStages":[]},"version":"v1","identity":"rs-7234753","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7234753","identity":"rs-7234753","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}