{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T19:49:06Z","timestamp":1788637746318,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T00:00:00Z","timestamp":1670716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"publisher","award":["E0.13"],"award-info":[{"award-number":["E0.13"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis, metabolic dysregulation, and neutrophilic inflammation. In this study, we hypothesized that systemic levels of plasma calprotectin, as a biomarker of neutrophilic inflammation, may be associated with suspected MAFLD. Plasma calprotectin levels were measured in subjects (n = 5446) participating in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort study. Suspected MAFLD was defined by the fatty liver index (FLI \u2265 60) and hepatic steatosis index (HSI \u2265 36) as proxies. Plasma calprotectin levels were significantly higher in subjects with FLI \u2265 60 (0.57 [IQR: 0.42\u20130.79] mg\/L, n = 1592) (p &lt; 0.001) compared to subjects with FLI &lt; 60 (0.46 [0.34\u20130.65] mg\/L, n = 3854). Multivariable logistic regression analyses revealed that plasma calprotectin levels were significantly associated with suspected MAFLD (FLI \u2265 60), even after adjustment for potential confounding factors, including current smoking, alcohol consumption, hypertension, diabetes, cardiovascular diseases, insulin resistance (HOMA-IR), hs-CRP, eGFR, and total cholesterol levels (OR 1.19 [95% CI: 1.06\u20131.33], p = 0.003). Interaction analyses revealed significant effect modifications for the association between plasma calprotectin and suspected MAFLD by BMI (p &lt; 0.001) and hypertension (p = 0.003), with the strongest associations in subjects with normal BMI and without hypertension. Prospectively, plasma calprotectin levels were significantly associated with all-cause mortality after adjustment for potential confounding factors, particularly in subjects without suspected MAFLD (FLI &lt; 60) (hazard ratio (HR) per doubling: 1.34 (1.05\u20131.72), p &lt; 0.05). In conclusion, higher plasma calprotectin levels are associated with suspected MAFLD and with the risk of all-cause mortality, the latter especially in subjects without suspected MAFLD.<\/jats:p>","DOI":"10.3390\/ijms232415708","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T01:42:27Z","timestamp":1670809347000},"page":"15708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Plasma Calprotectin Levels Associate with Suspected Metabolic-Associated Fatty Liver Disease and All-Cause Mortality in the General Population"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-3821","authenticated-orcid":false,"given":"Arno R.","family":"Bourgonje","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2703-2320","authenticated-orcid":false,"given":"Eline H.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyanne M.","family":"Kieneker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-6318","authenticated-orcid":false,"given":"Tom","family":"Nilsen","sequence":"additional","affiliation":[{"name":"Gentian AS, 1596 Moss, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Hidden","sequence":"additional","affiliation":[{"name":"Gentian AS, 1596 Moss, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4240-7506","authenticated-orcid":false,"given":"Hans","family":"Blokzijl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3844-5254","authenticated-orcid":false,"given":"Robin P. F.","family":"Dullaart","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-1577","authenticated-orcid":false,"given":"Harry","family":"van Goor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-2238","authenticated-orcid":false,"given":"Amaal E.","family":"Abdulle","sequence":"additional","affiliation":[{"name":"Department Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. 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