{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:12:45Z","timestamp":1790986365492,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T00:00:00Z","timestamp":1404432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Key Project of Chinese Ministry of Science and Technology","award":["2012ZX10002007"],"award-info":[{"award-number":["2012ZX10002007"]}]},{"name":"Key Project of Chinese Ministry of Science and Technology","award":["2013ZX10002001"],"award-info":[{"award-number":["2013ZX10002001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81171579"],"award-info":[{"award-number":["81171579"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81201287"],"award-info":[{"award-number":["81201287"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81201232"],"award-info":[{"award-number":["81201232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016694","name":"Science and Technology Development Plan of Shandong Province","doi-asserted-by":"crossref","award":["2012GSF11846"],"award-info":[{"award-number":["2012GSF11846"]}],"id":[{"id":"10.13039\/100016694","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The G\u2010protein\u2010coupled bile acid receptor Gpbar1 <jats:italic>(TGR5<\/jats:italic>) has been demonstrated to be able to negatively regulate hepatic inflammatory response. In this study, we aimed to determine the methylation status of <jats:italic>TGR5<\/jats:italic> promoter in patients with acute\u2010on\u2010chronic hepatitis B liver failure (<jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content>) and its predictive value for prognosis. We enrolled 76 consecutive <jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content> patients, 80 chronic hepatitis B (<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>) patients and 30 healthy controls (<jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>s). Methylation status of <jats:italic>TGR5<\/jats:italic> promoter in peripheral mononuclear cell (<jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>) was detected by methylation\u2010specific polymerase chain reaction (<jats:styled-content style=\"fixed-case\">MSP<\/jats:styled-content>). The <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level of <jats:italic>TGR5<\/jats:italic> was determined by quantitative real\u2010time polymerase chain reaction (RT\u2010<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>). We found that the frequency of <jats:italic>TGR5<\/jats:italic> promoter methylation was significantly higher in <jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content> (35\/76, 46.05%) than CHB patients (5\/80, 6.25%; <jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a032.38, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and HCs (1\/30, 3.33%; \u03c7<jats:sup>2<\/jats:sup>\u00a0=\u00a017.50, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). <jats:italic>TGR5 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level was significantly lower (<jats:italic>Z<\/jats:italic>\u00a0=\u00a0\u22129.12, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in participants with aberrant methylation than those without. <jats:italic>TGR5<\/jats:italic> methylation showed a sensitivity of 46.05% (35\/76), specificity of 93.75% (75\/80), positive predictive value (<jats:styled-content style=\"fixed-case\">PPV<\/jats:styled-content>) of 87.5% (35\/40) and negative predictive value (<jats:styled-content style=\"fixed-case\">NPV<\/jats:styled-content>) of 64.66% (75\/116) in discriminating <jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients. ACHBLF patients with methylated <jats:italic>TGR5<\/jats:italic> showed significantly poor survival than those without (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). When used to predict 3\u2010month mortality of <jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content>,<jats:italic> TGR5<\/jats:italic> methylation [area under the receiver operating characteristic curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>)\u00a0=\u00a00.75] performed significantly better than model for end\u2010stage liver diseases (<jats:styled-content style=\"fixed-case\">MELD<\/jats:styled-content>) score (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\u00a0=\u00a00.65; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Therefore, our study demonstrated that aberrant <jats:styled-content style=\"fixed-case\">TGR<\/jats:styled-content>5 promoter methylation occurred in <jats:styled-content style=\"fixed-case\">ACHBLF<\/jats:styled-content> and might be a potential prognostic marker for the disease.<\/jats:p>","DOI":"10.1111\/jvh.12277","type":"journal-article","created":{"date-parts":[[2014,7,4]],"date-time":"2014-07-04T06:22:54Z","timestamp":1404454974000},"page":"112-119","source":"Crossref","is-referenced-by-count":11,"title":["Aberrant <scp>DNA<\/scp> methylation of <scp>G<\/scp>\u2010protein\u2010coupled bile acid receptor <scp>G<\/scp>pbar1 predicts prognosis of acute\u2010on\u2010chronic hepatitis <scp>B<\/scp> liver failure"],"prefix":"10.1111","volume":"22","author":[{"given":"S.","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.\u2010F.","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.\u2010K.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u2010C.","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"},{"name":"Institute of Hepatology Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatology Qilu Hospital of Shandong University Jinan China"},{"name":"Institute of Hepatology Shandong University Jinan 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