2026-04-17T03:09:18Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/45882025-10-24T10:30:35Zcom_2072_378070com_2072_378040col_2072_378092

Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients Podlaha, Ondrej Gane, Edward Brunetto, Maurizia Chuang, Wan-Long Pan, Calvin Q. Fung, Scott Buti Ferret, Maria Genomes Hepatitis B Reaccions antígen-anticòs DISEASES::Virus Diseases::Virus Diseases::Hepatitis, Viral, Human::Hepatitis B::Hepatitis B, Chronic ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Sustained Virologic Response PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Structures::Genome::Genome, Microbial::Genome, Viral ENFERMEDADES::virosis::virosis::hepatitis viral humana::hepatitis B::hepatitis B crónica TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::respuesta virológica sostenida FENÓMENOS Y PROCESOS::fenómenos genéticos::estructuras genéticas::genoma::genoma microbiano::genoma viral Chronic hepatitis B; HBeAg status; Viral genome variation Hepatitis B crónica; Estado de HBeAg; Variación del genoma viral Hepatitis B crònica; Estat de HBeAg; Variació del genoma viral Despite 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. 2025-10-24T10:30:35Z 2025-10-24T10:30:35Z 2025-10-24T10:30:35Z 2020-02-05T11:23:33Z 2020-02-05T11:23:33Z 2019-07-19 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/4588 Scientific Reports;9(1) https://www.nature.com/articles/s41598-019-46609-7 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Springer Nature Scientia