{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:39:12Z","timestamp":1790721552518,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Volatile organic compound (VOC) exposure is an environmental health concern and could, through the liver exposome, be associated with metabolic dysfunction associated steatotic liver disease (MASLD) progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed NHANES 2017\u20132020, a U.S. population\u2010based cohort with controlled attenuation parameter (CAP), liver stiffness measurement (LSM) and urinary VOC metabolites. Participants with viral hepatitis, excess alcohol use or missing urine creatinine were excluded. MASLD was defined as CAP \u2265\u2009275\u2009dB\/m with metabolic dysfunction, at\u2010risk MASH as FAST \u2265\u20090.35 and increased LSM as \u2265\u20098\u2009kPa. Weighted quantile sum (WQS) regression assessed associations between VOC metabolites and outcomes, adjusting for age, sex, smoking and alcohol. Phenylglyoxylic acid (PGA) and mandelic acid (MA) were further examined using logistic regression for the MA\/(MA and PGA) ratio and human liver organoids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort comprised 2004 participants (41.4% MASLD, 5.4% at\u2010risk MASH, 9.7% LSM \u2265\u20098\u2009kPa). Higher VOC metabolite levels were associated with increased risk of MASLD (aOR 1.47 per quartile, 95% CI 1.06\u20132.04) and at\u2010risk MASH (aOR 2.69 per quartile, 95% CI 1.23\u20135.87), primarily driven by N\u2010Acetyl\u2010S\u2010(2\u2010carboxyethyl)\u2010L\u2010cysteine (CEMA) and N\u2010Acetyl\u2010S\u2010(3\u2010hydroxy\u20101\u2010methylpropyl)\u2010L\u2010cysteine (HMPMA), with inverse associations driven by PGA. No significant associations were found for increased LSM, yet a higher MA\/(MA\u2009+\u2009PGA) ratio was associated with increased risk for at\u2010risk MASH and LSM \u2265\u20098\u2009kPa. In human liver organoids, PGA exposure increased lipid droplet number and size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Urinary VOC metabolites show distinct associations with MASLD and at\u2010risk MASH in the general population. CEMA and HMPMA were associated with increased risk, consistent with prior links to metabolic dysfunction. PGA induced steatosis in liver organoids, suggesting poor metabolising of styrene and ethylbenzene and intracellular PGA accumulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70783","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:12:18Z","timestamp":1783426338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Urinary Volatile Organic Compound Metabolites Are Associated With\n                    <scp>MASLD<\/scp>\n                    \/\n                    <scp>MASH<\/scp>\n                    in Humans and Induce Steatosis in Liver Organoids"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-1182","authenticated-orcid":false,"given":"Laurens A.","family":"van Kleef","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Internal Medicine Ikazia Hospital, Center  Rotterdam the Netherlands"},{"name":"Department of Gastroenterology and Hepatology Ikazia Hospital, Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xincheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-4573","authenticated-orcid":false,"given":"Pengfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Ayada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-5205","authenticated-orcid":false,"given":"Yasir J.","family":"Abozaid","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC, University Medical Center  Rotterdam the Netherlands"},{"name":"Department of Microbiology and Pathology, College of Veterinary Medicine University of Duhok  Duhok Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5514-4874","authenticated-orcid":false,"given":"Jesse","family":"Pustjens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marike","family":"Wabbijn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ikazia Hospital, Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Bezemer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Ikazia Hospital, Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Ghanbari","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"van der Laan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC, University Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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