{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:02:43Z","timestamp":1790949763903,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We analyzed serum metabolome from 1154 individuals with biopsy\u2010proven NAFLD, and from four mouse models of NAFLD with impaired VLDL\u2010triglyceride (TG) secretion, and one with normal VLDL\u2010TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL\u2010TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL\u2010TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL\u2010TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL\u2010TG and VLDL\u2013apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL<jats:sub>5,6<\/jats:sub>, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10\u2010year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin\u2010like phospholipase domain\u2010containing protein 3 NAFLD risk allele were lower in subtype A.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32427","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T01:08:13Z","timestamp":1645924093000},"page":"1121-1134","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":66,"title":["Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles"],"prefix":"10.1097","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9483-8426","authenticated-orcid":false,"given":"Ibon","family":"Mart\u00ednez\u2010Arranz","sequence":"first","affiliation":[{"name":"OWL Metabolomics,Derio,Bizkaia,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bruzzone","sequence":"additional","affiliation":[{"name":"CIC 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