Sistema de Salut de Catalunya
Institut Català de la Salut
[Gregori J] Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ibañez-Lligoña M] Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Colomer-Castell S, Campos C] Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [García-Cehic D] Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. [Quer J] Grup de Recerca de les Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-01-15T07:43:52Z
2025-01-15T07:43:52Z
2024-10-31
Fibrosis; Liver damage; Quasispecies maturity
Fibrosi; Dany hepàtic; Maduresa de quasiespècies
Fibrosis; Daño hepático; Madurez de cuasiespecies
Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.
This study was partially supported by Plan Estratègic de Recerca i Innovació en Salut (PERIS)—Direcció General de Recerca i Innovació en Salut (DGRIS), Catalan Health Ministry, Generalitat de Catalunya; Centro para el Desarrollo Tecnológico Industrial (CDTI) of the Spanish Ministry of Economy and Business, grant number IDI-20200297; and Project PI22/00258 funded by Instituto de Salud Carlos III (ISCIII) and cofounded by the European Union. S.C.-C has received support from the Spanish Ministry of Education, grant FPU21/04150. M.I.-L. received the support of a fellowship from the “la Caixa” Foundation (ID 100010434), whose code is LCF/BQ/DR23/12000020. C.C. received a predoctoral fellowship from VHIR.
Article
Published version
English
Hepatitis C - Tractament; Hepatitis C - Prognosi; Hepatitis C - Aspectes genètics; Cirrosi hepàtica; Medicaments antivírics - Ús terapèutic; Resistència als medicaments; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Quasispecies; DISEASES::Digestive System Diseases::Liver Diseases::Liver Cirrhosis; DISEASES::Virus Diseases::Hepatitis, Viral, Human::Hepatitis C::Hepatitis C, Chronic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Treatment Failure; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::cuasiespecies; ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática; ENFERMEDADES::virosis::hepatitis viral humana::hepatitis C::hepatitis C crónica; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::fracaso del tratamiento
MDPI
Microorganisms;12(11)
https://doi.org/10.3390/microorganisms12112213
info:eu-repo/grantAgreement/ES/PEICTI2021-2023/PI22%2F00258
info:eu-repo/grantAgreement/ES/PEICTI2021-2023/FPU21%2F04150
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3436]
