{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:56:09Z","timestamp":1781186169315,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"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":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. Although genetic variants are linked to MASLD progression, whether their associations with fibrosis severity are consistent across clinical contexts remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cross\u2010sectional analysis of 6446 individuals with MASLD from a community\u2010based (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094477) and a tertiary\u2010care hepatology population (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091969) was conducted. Fibrosis severity was assessed using the fibrosis\u20104 (FIB\u20104) index. Associations between MASLD\u2010related genetic variants (\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      rs738409,\n                      <jats:italic>TM6SF2<\/jats:italic>\n                      rs58542926, and\n                      <jats:italic>MBOAT7<\/jats:italic>\n                      rs641738) and fibrosis were evaluated using multivariable logistic regression within each population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Advanced fibrosis was more prevalent in the tertiary\u2010care population than in the community\u2010based population (FIB\u20104\u2009&gt;\u20091.30: 34.5% vs. 41.2%; FIB\u20104\u2009\u2265\u20093.25: 8.4% vs. 0.4%).\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      rs738409 showed consistent associations with fibrosis severity in both populations, with markedly stronger effects in the tertiary\u2010care setting. In the community\u2010based population, the GG genotype was associated with significant fibrosis (FIB\u20104\u2009&gt;\u20091.30; adjusted OR 1.28; 95% CI, 1.03\u20131.60; P for trend\u2009=\u20090.015), but not with higher thresholds. In contrast, in the tertiary\u2010care population, the GG genotype was strongly associated with FIB\u20104\u2009&gt;\u20091.30 (OR 3.11; 95% CI, 2.23\u20134.34), and FIB\u20104\u2009\u2265\u20093.25 (OR 4.17; 95% CI, 2.60\u20136.67; all\n                      <jats:italic>P<\/jats:italic>\n                      for trend\u2009&lt;\u20090.001).\n                      <jats:italic>TM6SF2<\/jats:italic>\n                      rs58542926 showed modest associations only in the community\u2010based population, while\n                      <jats:italic>MBOAT7<\/jats:italic>\n                      rs641738 was not associated with fibrosis severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Genetic associations with fibrosis in MASLD appear to be context dependent.\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      rs738409 shows consistent but markedly greater effect sizes in tertiary\u2010care settings, suggesting that clinical and metabolic context may play an important role in modulating genetic risk beyond ancestry alone.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70675","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T08:52:49Z","timestamp":1778143969000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Setting Modulates the Association Between Genetic Variants and Fibrosis Severity Across the Spectrum of\n                    <scp>MASLD<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0222-2251","authenticated-orcid":false,"given":"Mei\u2010Hsuan","family":"Lee","sequence":"first","affiliation":[{"name":"The Global NASH\/MASH Council (GNC)  Washington DC USA"},{"name":"Institute 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University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia\u2010Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla","family":"de Avila","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC)  Washington DC USA"},{"name":"Beatty Liver and Obesity Research Program Inova Health System  Falls Church Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lam","sequence":"additional","affiliation":[{"name":"The Global NASH\/MASH Council (GNC)  Washington DC USA"},{"name":"Beatty Liver and Obesity Research Program Inova Health System  Falls Church Virginia 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