{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:09:22Z","timestamp":1793725762559,"version":"4.6.1"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24fk0210149s1101"],"award-info":[{"award-number":["24fk0210149s1101"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24fk0210149s0401"],"award-info":[{"award-number":["24fk0210149s0401"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22K08038"],"award-info":[{"award-number":["22K08038"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22K15974"],"award-info":[{"award-number":["22K15974"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Fibrosis\u20104 (FIB\u20104) index and genetic polymorphisms have been used in assessing the risk of liver\u2010related events (LRE) in metabolic dysfunction\u2010associated steatotic liver disease (MASLD). To establish a more efficient prediction strategy for LRE, we investigated a combined approach that uses the FIB\u20104 index and genetic polymorphisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 1304 Japanese patients with biopsy\u2010proven MASLD in this longitudinal multicenter cohort study.\n                      <jats:italic>PNPLA3, TM6SF2, GCKR<\/jats:italic>\n                      and\n                      <jats:italic>MBOAT7<\/jats:italic>\n                      genotypes were genotyped, and polygenic risk score high fat content (PRS\u2010HFC) were calculated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During the follow\u2010up period of 8.1\u2009year, 96 LRE occurred and 53 patients died.\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      ,\n                      <jats:italic>TM6SF2 and GCKR<\/jats:italic>\n                      genotypes were associated with LRE development. We divided patients into three groups based on the FIB\u20104 index and\n                      <jats:italic>PNPLA3<\/jats:italic>\n                      and\n                      <jats:italic>TM6SF2<\/jats:italic>\n                      genotype. The cumulative LRE development rate in each group was 2.1%\/28.9%\/53.5%, respectively, at 10\u2009years. Multivariate analysis revealed hazard ratios (HRs) for LRE of 10.72 in the high\u2010risk group and 4.80 in the intermediate\u2010risk group. Overall survival in each group was 98.8%\/85.2%\/72.4%, respectively, at 10\u2009years. HRs for prognosis were 8.74 in the high\u2010risk group and 5.62 in the intermediate\u2010risk group. Patients with FIB\u20104 index &gt;\u20092.67 and high PRS\u2010HFC had HR of 6.70 for LRE development and HR of 6.07 for prognosis compared to patients with FIB\u20104\u2009\u2264\u20092.67.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The approach of measuring the FIB\u20104 index first followed by assessment of genetic polymorphisms efficiently detected patients at high risk of developing LRE. Therefore, this two\u2010step strategy could be used as a screening method in large populations of patients with MASLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.16124","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T07:15:36Z","timestamp":1728285336000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Clinical Utility of Genetic Variants in\n                    <i>PNPLA3<\/i>\n                    and\n                    <i>TM6SF2<\/i>\n                    to Predict Liver\u2010Related Events in Metabolic Dysfunction\u2010Associated Steatotic Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-5894","authenticated-orcid":false,"given":"Yuya","family":"Seko","sequence":"first","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-046X","authenticated-orcid":false,"given":"Kanji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Molecular Gastroenterology and Hepatology, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Saiseikai Suita Hospital  Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michihiro","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine  Yokohama 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