{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:17:59Z","timestamp":1791152279934,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,1,21]],"date-time":"2015-01-21T00:00:00Z","timestamp":1421798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["320030_130243"],"award-info":[{"award-number":["320030_130243"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030B_147089"],"award-info":[{"award-number":["310030B_147089"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Differences in intrahepatic gene expression patterns may be associated with therapy response in peginterferon\u2010treated chronic hepatitis B (<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed gene expression profiling in baseline liver biopsies of 40 <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients (19 <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg\u2010positive; 21 <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg\u2010negative) treated with peginterferon and adefovir for 48\u00a0weeks, and compared expression patterns of combined responders (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg loss, <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> &lt;2000 <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/ml, alanine aminotransferase normalization after 1\u00a0year of treatment\u2010free follow\u2010up) with non\u2010responders. Genes identified by transcriptome analysis in 15 biopsies were confirmed in 25 additional biopsies by <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptome analysis demonstrated significant differences in expression of 41 genes between responders and non\u2010responders. In responders, pathway analysis showed specific upregulation of genes related to the immune response, including chemotaxis and antigen processing and presentation. Genes upregulated in responders exhibited strongest similarity with a set of genes induced in livers of chimpanzees with acute Hepatitis B infection. Differential expression was confirmed for eight selected genes. A 2\u2010gene subset (<jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DPB<\/jats:styled-content>1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">SERPIN<\/jats:styled-content>\u2010E1<\/jats:italic>) was found to predict response most accurately. Incorporation of these genes in a multivariable model with <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg status, <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> genotype and baseline <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>sAg level correctly classified 90% of all patients, in which <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">DPB<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SERPIN<\/jats:styled-content>\u2010E1<\/jats:italic> were independent predictors of response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified an intrahepatic transcriptional signature associated with enhanced immune activation which predicts therapy response. These novel associations could lead to better understanding of responsiveness to peginterferon in <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients, and may assist in selecting possible responders to interferon\u2010based treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12768","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T14:26:15Z","timestamp":1419258375000},"page":"1824-1832","source":"Crossref","is-referenced-by-count":21,"title":["An intrahepatic transcriptional signature of enhanced immune activity predicts response to peginterferon in chronic hepatitis B"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-7492","authenticated-orcid":false,"given":"Louis","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center (AMC) University of Amsterdam (UvA) Amsterdam The Netherlands"},{"name":"Department of Experimental Immunology AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annikki","family":"de Niet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center (AMC) University of Amsterdam (UvA) Amsterdam The Netherlands"},{"name":"Department of Experimental Immunology AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzanna","family":"Makowska","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Dill","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel A.","family":"van Dort","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology AMC Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeska","family":"Terpstra","sequence":"additional","affiliation":[{"name":"Department of Pathology Bronovo Hospital The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Bart Takkenberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center (AMC) University of Amsterdam (UvA) Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L.A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands"},{"name":"Liver Clinic Toronto Western and General Hospital University Health Network Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus 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