{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T23:37:00Z","timestamp":1776987420125,"version":"3.51.4"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM20162011"],"award-info":[{"award-number":["SZSM20162011"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM202211002"],"award-info":[{"award-number":["SZSM202211002"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sanming Project of Medicine in Shenzhen, Guangming","award":["szgmtd2025003"],"award-info":[{"award-number":["szgmtd2025003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sepsis-associated liver injury (SALI) is a highly heterogeneous thromboinflammatory disorder with no specific treatment. The De Ritis ratio (DRR, aspartate aminotransferase\/alanine aminotransferase) stratifies mortality risk, and unfractionated heparin (UFH) possesses pleiotropic effects that may attenuate thromboinflammation. We investigated whether DRR identifies a SALI subphenotype that derives differential benefit from UFH therapy.<\/jats:p>\n                  <jats:p>This retrospective multicenter cohort study included 9,561 SALI patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV; n\u2009=\u20096,133) and eICU-CRD (n\u2009=\u20093,428) databases. The primary outcome was intensive care unit (ICU) mortality. We employed propensity score matching (PSM) and marginal structural Cox models (MSCM) to adjust for baseline and time-varying confounders. Subgroup analyses evaluated the association between UFH and mortality across DRR strata, with formal testing for UFH\u2009\u00d7\u2009DRR interaction.<\/jats:p>\n                  <jats:p>UFH therapy was associated with significantly reduced ICU mortality after PSM in both cohorts MIMIC-IV (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.28\u20130.42) and eICU (HR: 0.43, 95% CI: 0.29\u20130.65), with consistent results in MSCM analyses (HR: 0.22, 95% CI: 0.17\u20130.30). Subgroup analysis suggested numerical benefit in patients with DRR\u2009&gt;\u20091, but formal tests for interaction were not significant in either cohort (MIMIC-IV: p\u2009=\u20090.111; eICU: p\u2009=\u20090.775).<\/jats:p>\n                  <jats:p>UFH therapy is associated with reduced mortality in SALI patients. Although DRR identifies a high-risk subgroup, the lack of significant interaction precludes its use as a predictive biomarker for UFH response. A prospective randomized trial is warranted to validate these findings and DRR-stratified UFH benefits.<\/jats:p>","DOI":"10.1055\/a-2852-9288","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T23:00:57Z","timestamp":1776985257000},"source":"Crossref","is-referenced-by-count":0,"title":["De Ritis Ratio and Heparin Therapy in Sepsis-Associated Liver Injury: A Multicenter Cohort Study"],"prefix":"10.1055","author":[{"given":"Bo","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medicine, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dazheng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Infection and Critical Care Medicine, Shenzhen Second People's Hospital & First Affiliated Hospital of Shenzhen University, Shenzhen, China"},{"name":"Department of Critical Care Medicine, Shenzhen University of Advanced Technology General Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyi","family":"Luan","sequence":"first","affiliation":[{"name":"Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajaganesh","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhong","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Infection and Critical Care Medicine, Shenzhen Second People's Hospital & First Affiliated Hospital of Shenzhen University, Shenzhen, China"},{"name":"Department of Hospital-Acquired Infection Control, Shenzhen Second People's Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Infection and Critical Care Medicine, Shenzhen Second People's Hospital & First Affiliated Hospital of Shenzhen University, Shenzhen, China"},{"name":"Department of Hospital-Acquired Infection Control, Shenzhen Second People's Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infection and Critical Care Medicine, Shenzhen Second People's Hospital & First Affiliated Hospital of Shenzhen University, Shenzhen, China"},{"name":"Department of Hospital-Acquired Infection Control, Shenzhen Second People's Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiye","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Shenzhen University of Advanced Technology General Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongming","family":"Yao","sequence":"additional","affiliation":[{"name":"Medical Innovation Research Department and Fourth Medical Center, the Chinese PLA General Hospital, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0800-5506","authenticated-orcid":false,"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infection and Critical Care Medicine, Shenzhen Second People's Hospital & First Affiliated Hospital of Shenzhen University, Shenzhen, China"},{"name":"Department of Hospital-Acquired Infection Control, Shenzhen Second People's Hospital, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"issue":"12","key":"ref1","doi-asserted-by":"crossref","first-page":"e2013","DOI":"10.1016\/S2214-109X(25)00356-0","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis","volume":"13","author":"G BDGS Collaborators","year":"2025","journal-title":"Lancet Glob Health"},{"key":"ref2","first-page":"e928928","article-title":"Sites and causes of infection in patients with sepsis-associated liver dysfunction: a population study from the medical information mart for intensive care III","volume":"27","author":"J Lin","year":"2021","journal-title":"Med Sci Monit"},{"issue":"06","key":"ref3","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3109\/08830185.2014.889129","article-title":"The role of the liver in sepsis","volume":"33","author":"J Yan","year":"2014","journal-title":"Int Rev 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