dc.description.abstract | Deletions in the 3′ end region of the hepatitis B virus (HBV) X open reading frame (HBX) may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions (Indels) in this region in the quasispecies of 50 chronic hepatitis B (CHB) patients without HCC. We identified 103 different Indels in 47 (94%) patients, in a median of 3.4% of their reads (IQR, 1.3–8.4%), and 25% (IQR, 13.1–40.7%) of unique sequences identified in each quasispecies (haplotypes). Of those Indels, 101 (98.1%) caused 44 different altered stop codons, the most commonly observed were at positions 128, 129, 135, and 362 (putative position). Moreover, 39 (37.9%) Indels altered the TATA-like box (TA) sequences of Cp; the most commonly observed caused TA2 + TA3 fusion, creating a new putative canonical TATA box. Four (8%) patients developed negative clinical outcomes after a median follow-up of 9.4 (8.7–12) years. In conclusion, we observed variants with Indels in the HBX 3′ end in the vast majority of our CHB patients, some of them encoding alternative versions of HBx with potential functional roles, and/or alterations in the regulation of transcription. |
dc.contributor.authoraffiliation | [García-García S, Pacin-Ruiz B, Rodriguez-Frias F] Unitat de Patologia Hepàtica, Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Caballero-Garralda A] Unitat de Patologia Hepàtica, Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Echevarne Laboratory, Department of Biochemistry, 08037 Barcelona, Spain. [Tabernero D, Cortese MF] Unitat de Patologia Hepàtica, Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain. [Gregori J] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Rodriguez-Algarra F] Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK. [Quer J] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Riveiro-Barciela M, Buti M] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain. Unitat Hepàtica, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Homs M] Anoia Primary Care Service, Territorial Management of Central Catalonia, Catalan Institute of Health, 08700 Igualada, Spain. Health Promotion in Rural Areas Research Group, Territorial Management of Central Catalonia, Catalan Institute of Health, 08272 Sant Fruitós de Bages, Spain. [Rando-Segura A] Unitat de Patologia Hepàtica, Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Vila M, Ferrer-Costa R] Unitat de Patologia Hepàtica, Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pumarola T] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain |