Nonlinear Association between AST/ALT Ratio and 28-Day Mortality in Critically Ill Cirrhotic Patients: A Retrospective Cohort Study

Nonlinear Association between AST/ALT Ratio and 28-Day Mortality in Critically Ill Cirrhotic Patients: A Retrospective Cohort Study | 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 Research Article Nonlinear Association between AST/ALT Ratio and 28-Day Mortality in Critically Ill Cirrhotic Patients: A Retrospective Cohort Study Zhigang Xu, Baohong Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6086517/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 May, 2025 Read the published version in BMC Gastroenterology → Version 1 posted 13 You are reading this latest preprint version Abstract Background The aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio is a biochemical marker that has been demonstrated in recent years to be significantly linked to unfavorable clinical outcomes across different patient populations. However, the function of this ratio in patients with severe cirrhosis remains to be elucidated. This study aimed to examine the link between the AST/ALT ratio and mortality among cirrhosis patients in the intensive care unit. Methods This retrospective cohort analysis utilized the MIMIC-IV database to study 2,090 liver cirrhosis patients with their first ICU admission between 2008 and 2019. The AST/ALT ratio, assessed within the initial 24 hours of ICU admission, served as the exposure variable. The primary outcome measure was ICU mortality at 28 days. A multivariate linear regression model was used to assess the relationship between the AST/ALT ratio and 28-day ICU mortality. Potential nonlinear relationships were examined through the use of smooth curve fitting techniques and saturation effect analyses. Furthermore, stratified analyses and interaction testing were conducted, with participants categorized according to demographic variables and clinical characteristics. Results The present study comprised 2,990 patients suffering from liver cirrhosis and classified as being in critical condition. The patients had a mean age of 59.1 years, with 65.0% being male, and an ICU mortality rate of 29.0%. After multivariate adjustment, the AST/ALT ratio was independently associated with 28-day ICU mortality in cirrhotic patients (OR = 1.1, 95% CI 1.0–1.2; p = 0.015). A nonlinear relationship was observed, with an inflection point at 3.6. Below this threshold, each unit increase was linked to a 40% higher mortality risk (OR = 1.4, 95% CI 1.2–1.6, p < 0.001), while the association leveled off beyond this point (OR = 1.0, 95% CI 0.8–1.1, p = 0.600). Subgroup analyses and interaction tests confirmed the consistent association between the AST/ALT ratio and 28-day ICU mortality, with all interaction P values exceeding 0.05. Conclusions The AST/ALT ratio independently predicts 28-day mortality in critically ill cirrhotic patients, exhibiting a non-linear association with short-term mortality. This discovery could enhance risk assessment in the ICU and inform clinical decisions. Cirrhosis AST/ALT ratio ICU mortality Prognosis Nonlinear association Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 13 May, 2025 Read the published version in BMC Gastroenterology → Version 1 posted Editorial decision: Revision requested 02 Apr, 2025 Reviews received at journal 01 Apr, 2025 Reviews received at journal 31 Mar, 2025 Reviews received at journal 31 Mar, 2025 Reviewers agreed at journal 31 Mar, 2025 Reviewers agreed at journal 30 Mar, 2025 Reviewers agreed at journal 20 Mar, 2025 Reviewers agreed at journal 20 Mar, 2025 Reviewers invited by journal 20 Mar, 2025 Editor invited by journal 27 Feb, 2025 Editor assigned by journal 26 Feb, 2025 Submission checks completed at journal 26 Feb, 2025 First submitted to journal 22 Feb, 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. 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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-6086517","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":437531691,"identity":"f9e6dbb4-f747-4281-8511-f5fe2008b72f","order_by":0,"name":"Zhigang Xu","email":"","orcid":"","institution":"Beijing Luhe Hospital Affiliated to Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhigang","middleName":"","lastName":"Xu","suffix":""},{"id":437531692,"identity":"5963c2e7-cc5e-4000-b2f7-b55ec227ea51","order_by":1,"name":"Baohong Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYBACAwkg8aHCBsplI1IL44wzaSRqYeZtO0yCFnPpHjMJHrbz8vzTzhgwfCg7zMA/uwG/Fss5x9IkJHhuG864nWPAOOPcYQaJOwcIOOxG8jEJA4nbCQbSOQZgFxpIJBDSktgmkWBwDqLlL3FagLYcSDgA0cJIjBbLGWnJlg0HkoF+SSs42HMunUfiBgEt5hI5hrf//rOT55+dvPHBjzJrOf4ZBLSggANAzEOC+lEwCkbBKBgFuAAAFzQ/5AGJJXsAAAAASUVORK5CYII=","orcid":"","institution":"Beijing Luhe Hospital Affiliated to Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Baohong","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-02-22 16:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6086517/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6086517/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-025-03966-0","type":"published","date":"2025-05-13T15:57:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83067847,"identity":"e14f76e4-5bec-4e25-9362-dbee191fb2d6","added_by":"auto","created_at":"2025-05-19 16:06:54","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":421293,"visible":true,"origin":"","legend":"","description":"","filename":"ASTALTRatioand28DayMortality.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6086517/v1_covered_a08e58d1-6ed9-4990-b052-a2af39ec5cfc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Nonlinear Association between AST/ALT Ratio and 28-Day Mortality in Critically Ill Cirrhotic Patients: A Retrospective Cohort Study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cirrhosis, AST/ALT ratio, ICU mortality, Prognosis, Nonlinear association","lastPublishedDoi":"10.21203/rs.3.rs-6086517/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6086517/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio is a biochemical marker that has been demonstrated in recent years to be significantly linked to unfavorable clinical outcomes across different patient populations. However, the function of this ratio in patients with severe cirrhosis remains to be elucidated. This study aimed to examine the link between the AST/ALT ratio and mortality among cirrhosis patients in the intensive care unit.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective cohort analysis utilized the MIMIC-IV database to study 2,090 liver cirrhosis patients with their first ICU admission between 2008 and 2019. The AST/ALT ratio, assessed within the initial 24 hours of ICU admission, served as the exposure variable. The primary outcome measure was ICU mortality at 28 days. A multivariate linear regression model was used to assess the relationship between the AST/ALT ratio and 28-day ICU mortality. Potential nonlinear relationships were examined through the use of smooth curve fitting techniques and saturation effect analyses. Furthermore, stratified analyses and interaction testing were conducted, with participants categorized according to demographic variables and clinical characteristics.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe present study comprised 2,990 patients suffering from liver cirrhosis and classified as being in critical condition. The patients had a mean age of 59.1 years, with 65.0% being male, and an ICU mortality rate of 29.0%. After multivariate adjustment, the AST/ALT ratio was independently associated with 28-day ICU mortality in cirrhotic patients (OR\u0026thinsp;=\u0026thinsp;1.1, 95% CI 1.0\u0026ndash;1.2; p\u0026thinsp;=\u0026thinsp;0.015). A nonlinear relationship was observed, with an inflection point at 3.6. Below this threshold, each unit increase was linked to a 40% higher mortality risk (OR\u0026thinsp;=\u0026thinsp;1.4, 95% CI 1.2\u0026ndash;1.6, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), while the association leveled off beyond this point (OR\u0026thinsp;=\u0026thinsp;1.0, 95% CI 0.8\u0026ndash;1.1, p\u0026thinsp;=\u0026thinsp;0.600). Subgroup analyses and interaction tests confirmed the consistent association between the AST/ALT ratio and 28-day ICU mortality, with all interaction P values exceeding 0.05.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe AST/ALT ratio independently predicts 28-day mortality in critically ill cirrhotic patients, exhibiting a non-linear association with short-term mortality. This discovery could enhance risk assessment in the ICU and inform clinical decisions.\u003c/p\u003e","manuscriptTitle":"Nonlinear Association between AST/ALT Ratio and 28-Day Mortality in Critically Ill Cirrhotic Patients: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 13:39:40","doi":"10.21203/rs.3.rs-6086517/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-02T15:28:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-01T22:27:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-31T14:37:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-31T14:20:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156490498093660249462826881113220787333","date":"2025-03-31T05:41:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78897670715236449363569897070810338244","date":"2025-03-30T23:32:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133467789993282536142751662088957724684","date":"2025-03-20T16:27:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"245414091612132309129624852159417387459","date":"2025-03-20T16:07:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-20T15:40:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-02-27T09:00:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-27T02:14:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-02-27T02:13:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2025-02-22T15:54:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1be1c021-8e89-40f1-9b2c-4b21bca93fce","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-19T16:01:53+00:00","versionOfRecord":{"articleIdentity":"rs-6086517","link":"https://doi.org/10.1186/s12876-025-03966-0","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2025-05-13 15:57:10","publishedOnDateReadable":"May 13th, 2025"},"versionCreatedAt":"2025-05-06 13:39:40","video":"","vorDoi":"10.1186/s12876-025-03966-0","vorDoiUrl":"https://doi.org/10.1186/s12876-025-03966-0","workflowStages":[]},"version":"v1","identity":"rs-6086517","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6086517","identity":"rs-6086517","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}