{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:59Z","timestamp":1790753819918,"version":"4.1.0"},"reference-count":34,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","gastrojournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gastroenterology"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1053\/j.gastro.2018.01.030","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T11:11:58Z","timestamp":1517397118000},"page":"1764-1777.e7","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":147,"title":["TLR7 Agonist Increases Responses of Hepatitis B Virus\u2013Specific T Cells and Natural Killer Cells in Patients With Chronic Hepatitis B Treated With Nucleos(T)Ide Analogues"],"prefix":"10.1053","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-5180","authenticated-orcid":false,"given":"Carolina","family":"Boni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Vecchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Laccabue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Giuberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Alfieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Lampertico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Grossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-4744","authenticated-orcid":false,"given":"Floriana","family":"Facchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizia R.","family":"Brunetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-8131","authenticated-orcid":false,"given":"Barbara","family":"Coco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-9571","authenticated-orcid":false,"given":"Daniela","family":"Cavallone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mangia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6516-1305","authenticated-orcid":false,"given":"Rosanna","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-0138","authenticated-orcid":false,"given":"Valeria","family":"Piazzolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Gaggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Mani","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1053\/j.gastro.2018.01.030_bib1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nrgastro.2016.7","article-title":"Global strategies are required to cure and eliminate HBV infection","volume":"13","author":"Revill","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","author":"Lampertico","year":"2017","journal-title":"J\u00a0Hepatol"},{"issue":"Suppl 1","key":"10.1053\/j.gastro.2018.01.030_bib3","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.jhep.2016.02.016","article-title":"New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus","volume":"64","author":"Durantel","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib4","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jhep.2016.05.043","article-title":"Aiming for cure in HBV and HDV infection","volume":"65","author":"Petersen","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib5","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/j.jhep.2016.01.026","article-title":"Adaptive immunity in HBV infection","volume":"64","author":"Bertoletti","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib6","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/j.jhep.2016.01.028","article-title":"The role of innate immunity in the immunopathology and treatment of HBV infection","volume":"64","author":"Maini","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ni1303","article-title":"Innate immune recognition of viral infection","volume":"7","author":"Kawai","year":"2006","journal-title":"Nat Immunol"},{"issue":"5963","key":"10.1053\/j.gastro.2018.01.030_bib8","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1126\/science.1183021","article-title":"Regulation of adaptive immunity by the innate immune system","volume":"327","author":"Iwasaki","year":"2010","journal-title":"Science"},{"key":"10.1053\/j.gastro.2018.01.030_bib9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nri2780","article-title":"Cross-priming in health and disease","volume":"10","author":"Kurts","year":"2010","journal-title":"Nar Rev Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib10","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1124\/jpet.113.207878","article-title":"Pharmacokinetic and pharmacodynamics properties of GS-9620, a novel TLR7 agonist, demonstrates ISG induction without detectable serum interferon at low oral doses","volume":"348","author":"Fosdick","year":"2014","journal-title":"J\u00a0Pharmacol Exp Ther"},{"key":"10.1053\/j.gastro.2018.01.030_bib11","first-page":"559","article-title":"Interferon-inducible antiviral effectors","volume":"8","author":"Sadler","year":"2008","journal-title":"Nat Rev"},{"key":"10.1053\/j.gastro.2018.01.030_bib12","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1172\/JCI58847","article-title":"IFNalpha inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome","volume":"122","author":"Belloni","year":"2012","journal-title":"J\u00a0Clin Invest"},{"key":"10.1053\/j.gastro.2018.01.030_bib13","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.tim.2005.01.006","article-title":"Pathogen-induced private conversations between natural killer and dendritic cells","volume":"13","author":"Della Chiesa","year":"2005","journal-title":"Trends Microbiol"},{"key":"10.1053\/j.gastro.2018.01.030_bib14","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.4049\/jimmunol.1300787","article-title":"Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen cross-presentation and robust type I IFN secretion","volume":"191","author":"Tel","year":"2013","journal-title":"J\u00a0Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib15","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.4049\/jimmunol.174.7.4043","article-title":"Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN","volume":"174","author":"Bekeredjian-Ding","year":"2005","journal-title":"J\u00a0Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib16","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.jhep.2014.12.026","article-title":"Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B","volume":"62","author":"Menne","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib17","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1053\/j.gastro.2013.02.003","article-title":"GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees","volume":"144","author":"Lanford","year":"2013","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2018.01.030_bib18","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1053\/j.gastro.2012.07.014","article-title":"Restored function of HBV-specific T cells after long-term effective therapy with nucleos(t)ide analogues","volume":"143","author":"Boni","year":"2012","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2018.01.030_bib19","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jhep.2017.10.027","article-title":"Safety, efficacy and pharmacodynamics of vesatolimod (GS-9620) in virally-suppressed patients with chronic hepatitis B","volume":"68","author":"Janssen","year":"2018","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib20","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/hep.28155","article-title":"Natural killer cell phenotype modulation and natural killer\/T-cell interplay in nucleos(t)ide analogue-treated hepatitis e antigen-negative patients with chronic hepatitis B","volume":"62","author":"Boni","year":"2015","journal-title":"Hepatology"},{"key":"10.1053\/j.gastro.2018.01.030_bib21","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2013.00057","article-title":"NK cells: a double-edged sword in chronic hepatitis B virus infection","volume":"4","author":"Maini","year":"2013","journal-title":"Front Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib22","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nm.3251","article-title":"Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells","volume":"19","author":"Rehermann","year":"2013","journal-title":"Nat Med"},{"key":"10.1053\/j.gastro.2018.01.030_bib23","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2014.00258","article-title":"The role of natural killer cells and CD8+ T cells in hepatitis B virus infection","volume":"5","author":"Schuch","year":"2014","journal-title":"Front Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.it.2014.11.001","article-title":"NK cells regulating T\u00a0cell responses: mechanisms and outcome","volume":"36","author":"Crouse","year":"2015","journal-title":"Trends Immunol"},{"issue":"12","key":"10.1053\/j.gastro.2018.01.030_bib25","doi-asserted-by":"crossref","first-page":"e1001227","DOI":"10.1371\/journal.ppat.1001227","article-title":"Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection","volume":"6","author":"Peppa","year":"2010","journal-title":"PLoS Pathog"},{"key":"10.1053\/j.gastro.2018.01.030_bib26","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1053\/j.gastro.2009.05.047","article-title":"Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections","volume":"137","author":"Oliviero","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1053\/j.gastro.2018.01.030_bib27","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1182\/blood-2010-08-300954","article-title":"DNAM-1 ligand expression on Ag-stimulated T lymphocytes is mediated by ROS-dependent activation of DNA-damage response: relevance for NK-T cell interaction","volume":"117","author":"Ardolino","year":"2011","journal-title":"Blood"},{"key":"10.1053\/j.gastro.2018.01.030_bib28","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1182\/blood-2006-10-052720","article-title":"Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM\/ATR-dependent mechanism and become susceptible to autologous NK-cell lysis","volume":"110","author":"Cerboni","year":"2007","journal-title":"Blood"},{"key":"10.1053\/j.gastro.2018.01.030_bib29","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.4049\/jimmunol.1601313","article-title":"T\u00a0cells infiltrating diseased liver express ligands for the NKG2D stress surveillance system","volume":"198","author":"Huang","year":"2017","journal-title":"J\u00a0Immunol"},{"key":"10.1053\/j.gastro.2018.01.030_bib30","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.immuni.2014.05.003","article-title":"Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1","volume":"40","author":"Crouse","year":"2014","journal-title":"Immunity"},{"key":"10.1053\/j.gastro.2018.01.030_bib31","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1182\/blood-2008-06-165944","article-title":"Detuning CD8+\u00a0T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells","volume":"113","author":"Cerboni","year":"2009","journal-title":"Blood"},{"key":"10.1053\/j.gastro.2018.01.030_bib32","article-title":"Anti-HBV response to Toll-like receptor 7 agonist GS-9620 is associated with intrahepatic aggregates of T cells and B cells","author":"Li","year":"2017","journal-title":"J\u00a0Hepatol"},{"key":"10.1053\/j.gastro.2018.01.030_bib33","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/ni.2573","article-title":"Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection","volume":"14","author":"Huang","year":"2013","journal-title":"Nat Immunol"},{"issue":"Suppl 1","key":"10.1053\/j.gastro.2018.01.030_bib34","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/liv.12064","article-title":"Why do I treat HBeAg-negative chronic hepatitis B patients with pegylated interferon?","volume":"33","author":"Lampertico","year":"2013","journal-title":"Liver Int"}],"container-title":["Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508518300726?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0016508518300726?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T15:20:19Z","timestamp":1758036019000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0016508518300726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["S0016508518300726"],"URL":"https:\/\/doi.org\/10.1053\/j.gastro.2018.01.030","relation":{},"ISSN":["0016-5085"],"issn-type":[{"value":"0016-5085","type":"print"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TLR7 Agonist Increases Responses of Hepatitis B Virus\u2013Specific T Cells and Natural Killer Cells in Patients With Chronic Hepatitis B Treated With Nucleos(T)Ide Analogues","name":"articletitle","label":"Article Title"},{"value":"Gastroenterology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1053\/j.gastro.2018.01.030","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 by the AGA Institute","name":"copyright","label":"Copyright"}]}}