{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:55:11Z","timestamp":1792796111674,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,9,25]],"date-time":"2016-09-25T00:00:00Z","timestamp":1474761600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC). Previously, we reported that DNA oxidation induced epigenetic alteration of tumor suppressor genes (TSGs) and contributed to HCC emergence. Here, we examine the associations between clinicopathological characteristics of NAFLD and advanced oxidative DNA damage that is associated with TSG methylation in the NAFLD liver.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Liver biopsies from 65 NAFLD patients were analyzed for clinicopathological features and oxidative DNA damage using immunohistochemistry of 8\u2010hydroxydeoxyguanosine (8\u2010OHdG). Abnormal DNA methylation in the promoters of 6 TSGs,\n                      <jats:italic>HIC1<\/jats:italic>\n                      ,\n                      <jats:italic>GSTP1<\/jats:italic>\n                      ,\n                      <jats:italic>SOCS1<\/jats:italic>\n                      ,\n                      <jats:italic>RASSF1<\/jats:italic>\n                      ,\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      , and\n                      <jats:italic>APC<\/jats:italic>\n                      , was examined using MethyLight. Associations between clinicopathological characteristics, methylation of TSGs, and accumulation of 8\u2010OHdG were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that aspartate aminotransferase\/alanine aminotransferase ratio, the fibrosis\u20104 index, and serum \u03b1\u2010fetoprotein (AFP) level were associated with degree of 8\u2010OHdG, and AFP was an independent factor among them (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0271). Regarding pathological findings, hepatocellular ballooning and stage of fibrosis were also associated with oxidative DNA damage (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0021 and 0.0054); ballooning was an independent risk for detecting high degree of 8\u2010OHdG in hepatocytes (odds ratio 7.38, 95% confidence interval 1.41\u201049.13,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0171). Accumulation of methylated TSGs was significantly associated with deposition of 8\u2010OHdG (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0362).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with high serum AFP and high degree of ballooning showed accumulation of oxidative DNA damage that could be a seed of DNA methylation responsible for hepatocarcinogenesis. These characteristics could be risk of HCC; such patients require urgent intervention such as lifestyle modification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.13318","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T08:24:39Z","timestamp":1455524679000},"page":"1646-1653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Unique features associated with hepatic oxidative DNA damage and DNA methylation in non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"31","author":[{"given":"Naoshi","family":"Nishida","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Yada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kitano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Kinki University Faculty of Medicine Osaka\u2010sayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25762"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0025-6196(24)00530-5","article-title":"Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease","volume":"55","author":"Ludwig J","year":"1980","journal-title":"Mayo Clin. 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