{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:44:20Z","timestamp":1776789860649,"version":"3.51.2"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,3,4]],"date-time":"2016-03-04T00:00:00Z","timestamp":1457049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Current treatment for chronic hepatitis B infection (<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>) consists of interferon\u2010based therapy. However, for unknown reasons, a large proportion of patients with <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content><\/jats:italic> genotypes were associated with treatment outcome for <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>. Twelve <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in or near the <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C<\/jats:italic> gene were genotyped in 86 <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients (41 <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg positive; 45 <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg negative) treated with peginterferon alfa\u20102a + adefovir. Genotyping of killer immunoglobin\u2010like receptors (<jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content>s) was performed by <jats:styled-content style=\"fixed-case\">SSP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. One <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> in <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C<\/jats:italic> (rs2308557) was significantly associated with combined response in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg\u2010positive <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients (<jats:italic>P<\/jats:italic> = 0.003). This <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> is linked to the <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C group C1 or C2 classification, which controls <jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content> binding. The combination of <jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">DL<\/jats:styled-content>1 with its ligand <jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C2 was observed significantly more often in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg\u2010positive patients with a combined response (13\/14) than in nonresponders (11\/27, <jats:italic>P<\/jats:italic> = 0.001). Patients with the <jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">DL<\/jats:styled-content>1\/C2 genotype had significantly higher baseline <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> levels (136 <jats:italic>vs<\/jats:italic> 50 U\/L, <jats:italic>P<\/jats:italic> = 0.002) than patients without this combination. Furthermore, <jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content>2<jats:styled-content style=\"fixed-case\">DL<\/jats:styled-content>1\u2010C2 predicted response independent of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> genotype and <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> at baseline. <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content><\/jats:italic> genotype is strongly associated with response in <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg\u2010positive <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients treated with interferon\u2010based therapy. In combination with other known response markers, <jats:italic><jats:styled-content style=\"fixed-case\">HLA<\/jats:styled-content>\u2010C\/<jats:styled-content style=\"fixed-case\">KIR<\/jats:styled-content><\/jats:italic> genotype could enable the selection of patients more likely to respond to interferon\u2010based therapy.<\/jats:p>","DOI":"10.1111\/jvh.12525","type":"journal-article","created":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T07:36:36Z","timestamp":1457249796000},"page":"652-659","source":"Crossref","is-referenced-by-count":10,"title":["<i><scp>HLA<\/scp>\u2010C<\/i> and <i><scp>KIR<\/scp><\/i> combined genotype as new response marker for <scp>HB<\/scp>eAg\u2010positive chronic hepatitis B patients treated with interferon\u2010based combination therapy"],"prefix":"10.1111","volume":"23","author":[{"given":"F.","family":"Stelma","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam the Netherlands"},{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam the Netherlands"},{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Sinnige","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. A.","family":"van Dort","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. B.","family":"Takkenberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. L. A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus Medical Center Rotterdam the Netherlands"},{"name":"Toronto Centre for Liver Disease Toronto Western &amp; General Hospital University Health Network Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. W.","family":"Reesink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Academic Medical Center Amsterdam the Netherlands"},{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. A.","family":"Kootstra","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology Academic Medical Center Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.12.116"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880515)61:10<1942::AID-CNCR2820611003>3.0.CO;2-J"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2580"},{"key":"e_1_2_11_6_1","first-page":"294A","article-title":"193 HBsAg loss with Tenofovir Disoproxil Fumarate (TDF) plus Peginterferon alfa\u20102a (PEG) in Chronic Hepatitis B (CHB): results of a global randomized controlled trial","volume":"60","author":"Marcellin P","year":"2014","journal-title":"Hepatology"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70289-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv180"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.029"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2011.03422.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3280-9"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1097670"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001092"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2809"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27794"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.004"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn564"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06258"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002877"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-362-6_25"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.3.913"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301580"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80127-8"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1991.tb05802.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03847"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.06.013"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.061"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2707"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26436"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.03.006"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25749"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23722"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.07.017"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22744"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12525","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12525","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12525","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T11:30:02Z","timestamp":1696246202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,4]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1111\/jvh.12525"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12525","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,4]]}}}