{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:23Z","timestamp":1783919063848,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is associated with adverse outcomes in sepsis, but risk stratification within MASLD remains insufficiently defined. We investigated whether an admission liver\u2013metabolic phenotype framework combining cardiometabolic burden with liver injury\/fibroinflammatory risk markers identifies clinically relevant organ-support vulnerability in community-acquired sepsis. Methods: This secondary analysis of the prospective SepsisFAT cohort (378 adults with community-acquired sepsis) classified patients into four phenotypes by cardiometabolic burden (\u22652 of: diabetes, hypertension, dyslipidemia, BMI \u2265 30 kg\/m2) and liver-risk positivity (FIB-4 \u2265 2.67, APRI \u2265 1.0, liver stiffness \u2265 10 kPa, or FAST \u2265 0.55). The primary outcome was acute kidney injury (AKI), while continuous renal replacement therapy (CRRT), other organ-support outcomes and in-hospital mortality were secondary endpoints. Results: Phenotype distribution was Low-risk 137 (36.2%), Cardiometabolic-only 84 (22.2%), Liver-dominant 88 (23.3%), and Mixed liver\u2013cardiometabolic 69 (18.3%). AKI and CRRT increased across phenotypes (13.9% to 40.6% and 5.1% to 26.1%, respectively), and in-hospital mortality was highest in the Mixed phenotype (26.1%). After Firth-penalized adjustment for age, sex, and admission SOFA, the Mixed phenotype remained independently associated with AKI (aOR 2.82, 95% CI 1.37\u20135.90) and CRRT (aOR 3.87, 1.50\u201310.80), confirmed in non-renal SOFA and admission eGFR-adjusted sensitivity analyses. Cardiometabolic burden alone did not confer excess organ-support risk. The same gradient persisted within the MASLD subgroup. Conclusions: Admission liver\u2013metabolic phenotyping identified a renal-vulnerable sepsis subgroup not captured by binary MASLD classification alone. These findings support prospective, multicenter external validation of liver\u2013metabolic phenotyping as a pragmatic approach to renal risk stratification in community-acquired sepsis.<\/jats:p>","DOI":"10.3390\/metabo16070468","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T12:01:37Z","timestamp":1783339297000},"page":"468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver\u2013Metabolic Phenotypes and Renal Vulnerability in Community-Acquired Sepsis: Insights from the SepsisFAT Cohort"],"prefix":"10.3390","volume":"16","author":[{"given":"Lara","family":"\u0160amadan Markovi\u0107","sequence":"first","affiliation":[{"name":"Croatian Institute of Public Health, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Pani\u0107","sequence":"additional","affiliation":[{"name":"Emergency Infectious Diseases Department, University Hospital for Infectious Diseases \u201cDr. Fran Mihaljevi\u0107\u201d, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juraj","family":"Krznari\u0107","sequence":"additional","affiliation":[{"name":"Department for Intensive Care, University Hospital for Infectious Diseases \u201cDr. Fran Mihaljevi\u0107\u201d, 10000 Zagreb, Croatia"},{"name":"Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8826-0741","authenticated-orcid":false,"given":"Branimir","family":"Gjura\u0161in","sequence":"additional","affiliation":[{"name":"Department for Intensive Care, University Hospital for Infectious Diseases \u201cDr. Fran Mihaljevi\u0107\u201d, 10000 Zagreb, Croatia"},{"name":"Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5784-1343","authenticated-orcid":false,"given":"Neven","family":"Papi\u0107","sequence":"additional","affiliation":[{"name":"Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department for Viral Hepatitis, University Hospital for Infectious Diseases \u201cDr. Fran Mihaljevi\u0107\u201d, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"ref_1","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2024). 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