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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorPodlaha, Ondrej
dc.contributor.authorGane, Edward
dc.contributor.authorBrunetto, Maurizia
dc.contributor.authorFung, Scott
dc.contributor.authorChuang, Wan-Long
dc.contributor.authorPan, Calvin Q.
dc.contributor.authorButi Ferret, Maria
dc.date.accessioned2020-02-05T11:23:33Z
dc.date.available2020-02-05T11:23:33Z
dc.date.issued2019-07-19
dc.identifier.citationPodlaha O, Gane E, Brunetto M, Fung S, Chuang WL, Pan CQ, et al. Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients. Sci Rep. 2019 Jul 19;9(1):10529.
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/11351/4588
dc.descriptionChronic hepatitis B; HBeAg status; Viral genome variation
dc.description.abstractDespite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to the negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.
dc.language.isoeng
dc.publisherSpringer Nature
dc.relation.ispartofseriesScientific Reports;9(1)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectGenomes
dc.subjectHepatitis B
dc.subjectReaccions antígen-anticòs
dc.subject.meshHepatitis B, Chronic
dc.subject.meshSustained Virologic Response
dc.subject.meshGenome, Viral
dc.titleLarge-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41598-019-46609-7
dc.subject.decshepatitis B crónica
dc.subject.decsrespuesta virológica sostenida
dc.subject.decsgenoma viral
dc.relation.publishversionhttps://www.nature.com/articles/s41598-019-46609-7
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.authoraffiliation[Podlaha O] Gilead Sciences Inc., 333 Lakeside Drive, Foster City, USA. [Gane E] Auckland Clinical Studies, Auckland, New Zealand. [Brunetto M] Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. Liver Unit, University Hospital of Pisa Hepatology Unit, University Hospital of Pisa, Pisa, Italy. [Fung S] Toronto General Hospital, Toronto, ON, Canada. [Chuang WL] Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. [Pan CQ] Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU School of Medicine, New York, NY, USA. [Buti M] Servei de Medicina Interna, Malalties Hepàtiques, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas (CIBEREHD), Instituto Carlos III (ISCIII), Madrid, Spain.
dc.identifier.pmid31324819
dc.identifier.wos000476468700057
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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