{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:09:44Z","timestamp":1790114984275,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,24]],"date-time":"2014-10-24T00:00:00Z","timestamp":1414108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Netherlands Genomics Initiative","award":["FES0908"],"award-info":[{"award-number":["FES0908"]}]},{"name":"Dutch government","award":["FES0908"],"award-info":[{"award-number":["FES0908"]}]},{"name":"Dutch government","award":["050-060-452"],"award-info":[{"award-number":["050-060-452"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Abstract<\/jats:title>Background & Aims<\/jats:title>We aimed to assess the association between the patatin\u2010like phospholipase domain\u2010containing\u20103 (PNPLA<\/jats:styled-content>3<\/jats:italic>) I148M polymorphism, liver histology and long\u2010term outcome in chronic hepatitis B (CHB<\/jats:styled-content>) patients.<\/jats:p><\/jats:sec>Methods<\/jats:title>We enrolled 531 consecutive treatment na\u00efve CHB<\/jats:styled-content> patients diagnosed from 1985 to 2012 with an available liver biopsy for reassessment, and sample for genetic testing. Data on all\u2010cause mortality and hepatocellular carcinoma (HCC<\/jats:styled-content>) at long\u2010term follow\u2010up were obtained from national database registries.<\/jats:p><\/jats:sec>Results<\/jats:title>The prevalence of steatohepatitis increased with PNPLA<\/jats:styled-content>3 <\/jats:italic>CC<\/jats:styled-content> (14%), CG<\/jats:styled-content> (20%) and GG<\/jats:styled-content> (43%) (P<\/jats:italic>\u00a0<\u00a00.001). The association was altered by both gender (P<\/jats:italic>\u00a0=\u00a00.010) and overweight (P<\/jats:italic>\u00a0=\u00a00.015): the effect of PNPLA<\/jats:styled-content>3<\/jats:italic> on steatohepatitis was most pronounced among non\u2010overweight females (adjusted OR<\/jats:styled-content> 13.4, 95%CI<\/jats:styled-content>: 3.7\u201351.6, P<\/jats:italic>\u00a0<\u00a00.001), and non\u2010overweight males (adjusted OR<\/jats:styled-content> 2.4, 95%CI<\/jats:styled-content>: 1.4\u20134.3, P<\/jats:italic>\u00a0=\u00a00.002). Furthermore, PNPLA<\/jats:styled-content>3 <\/jats:italic>GG<\/jats:styled-content> genotype was associated with iron depositions (OR<\/jats:styled-content> 2.8, 95%CI<\/jats:styled-content>: 1.2\u20136.4, P<\/jats:italic>\u00a0=\u00a00.014) and lobular inflammation (OR<\/jats:styled-content> 2.2, 95%CI<\/jats:styled-content>: 1.1\u20134.5, P<\/jats:italic>\u00a0=\u00a00.032), but not with advanced fibrosis (OR<\/jats:styled-content> 1.1, 95%CI<\/jats:styled-content>: 0.7\u20131.8, P<\/jats:italic>\u00a0=\u00a00.566). The median follow\u2010up was 10.1\u00a0years (interquartile range 5.6 \u2013 15.8), during which 13 patients developed HCC<\/jats:styled-content> and 28 died. Steatohepatitis was associated with all\u2010cause mortality [Hazard ratio (HR<\/jats:styled-content>) 3.1, 95%CI<\/jats:styled-content>: 1.3\u20137.3, P<\/jats:italic>\u00a0=\u00a00.006] and HCC<\/jats:styled-content> (HR<\/jats:styled-content> 2.8, 95%CI<\/jats:styled-content>: 0.9\u20139.2, P<\/jats:italic>\u00a0=\u00a00.078), but no significant association was observed for PNPLA<\/jats:styled-content>3<\/jats:italic>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>In this cohort of biopsied CHB<\/jats:styled-content> patients, PNPLA<\/jats:styled-content>3<\/jats:italic> was independently associated with steatosis, steatohepatitis, lobular inflammation and iron depositions, but not with advanced fibrosis, HCC<\/jats:styled-content> development or all\u2010cause mortality. The effect of PNPLA<\/jats:styled-content>3<\/jats:italic> on steatohepatitis was particularly pronounced among female patients without severe overweight.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12695","type":"journal-article","created":{"date-parts":[[2014,10,5]],"date-time":"2014-10-05T11:38:41Z","timestamp":1412509121000},"page":"438-447","source":"Crossref","is-referenced-by-count":28,"title":["The impact of PNPLA<\/scp>3<\/i> (rs738409<\/i> C>G) polymorphisms on liver histology and long\u2010term clinical outcome in chronic hepatitis B patients"],"prefix":"10.1111","volume":"35","author":[{"given":"Willem P","family":"Brouwer","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan J","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Boonstra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan D","family":"Pas","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"de Knegt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob A","family":"de Man","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina E","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"},{"name":"Department of Public Health Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiebo JW","family":"ten Kate","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus MC university Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry LA","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"},{"name":"UHN Liver Clinic Toronto Western and General Hospital University Health Network Toronto Toronto 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