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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Aldunate Caramori, Fabián | - |
dc.contributor.author | Echeverría Chagas, Natalia | - |
dc.contributor.author | Chiodi, Daniela | - |
dc.contributor.author | López, Pablo | - |
dc.contributor.author | Sánchez-Cicerón, Adriana | - |
dc.contributor.author | Soñora, Martín | - |
dc.contributor.author | Cristina, Juan | - |
dc.contributor.author | Moratorio, Gonzalo | - |
dc.contributor.author | Hernández, Nelia | - |
dc.contributor.author | Moreno Karlen, María del Pilar | - |
dc.date.accessioned | 2023-02-08T14:38:38Z | - |
dc.date.available | 2023-02-08T14:38:38Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Aldunate Caramori, F, Echeverría Chagas, N, Chiodi, D [y otros autores]. "Resistance-associated substitutions and response to treatment in a chronic hepatitis C virus infected-patient: an unusual virological response case report". BMC Infectious Diseases. [en línea] 2021, 21: 387. 6 h. DOI: 10.1186/s12879-021-06080-0. | es |
dc.identifier.issn | 1471-2334 | - |
dc.identifier.uri | https://hdl.handle.net/20.500.12008/35752 | - |
dc.description.abstract | Background: Direct-Acting agents (DAAs) target and inhibit essential viral replication proteins. They have revolutionized the treatment of Hepatitis C virus (HCV) infection reaching high levels of sustained virologic response. However, the detection of basal resistance-associated substitutions (RASs) to DAAs in naïve patients could be important in predicting the treatment outcome in some patients exhibiting failures to DAA-based therapies. Therefore, the aim of this work was to evaluate the presence of RASs as minority variants within intra-host viral populations, and assess their relationship to response to therapy on a multiple times relapser patient infected chronically with HCV. Case presentation: A male HCV infected-patient with a genotype 1a strain was evaluated. He had previously not responded to dual therapy (pegylated interferon-α plus ribavirin) and was going to start a direct-acting agent-based therapy (DAAs). He showed no significant liver fibrosis (F0). Viral RNA was extracted from serum samples taken prior and after therapy with DAAs (sofosbubir/ledipasvir/ribavirin). NS5A and NS5B genomic regions were PCR-amplified and the amplicons were sequenced using Sanger and next-generation sequencing (NGS) approaches. RASs were searched in in-silico translated sequences for all DAAs available and their frequencies were determined for those detected by NGS technology. Sanger sequencing did not reveal the presence of RASs in the consensus sequence neither before nor after the DAA treatment. However, several RASs were found at low frequencies, both before as well as after DAA treatment. RASs found as minority variants (particularly substitutions in position 93 within NS5A region) seem to have increased their frequency after DAA pressure. Nevertheless, these RASs did not become dominant and the patient still relapsed, despite perfect adherence to treatment and having no other complications beyond the infection (no significant fibrosis, no drug abuse). Conclusions: This report shows that some patients might relapse after a DAA-based therapy even when RASs (pre- and post-treatment) are detected in very low frequencies (< 1%) within intra-host viral populations. Increased awareness of this association may improve detection and guide towards a personalized HCV treatment, directly improving the outcome in hard-to-treat patients. | es |
dc.description.sponsorship | ANII: FMV_1_2014_1_104171 | es |
dc.format.extent | 6 h | es |
dc.format.mimetype | application/pdf | es |
dc.language.iso | en | es |
dc.publisher | BMC | es |
dc.relation.ispartof | BMC Infectious Diseases, 2021, 21: 387. | es |
dc.rights | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
dc.subject | DAA therapy | es |
dc.subject | Hepatitis C virus | es |
dc.subject | RASs minority variants | es |
dc.subject | Relapse | es |
dc.subject | Case report | es |
dc.title | Resistance-associated substitutions and response to treatment in a chronic hepatitis C virus infected-patient: an unusual virological response case report | es |
dc.type | Artículo | es |
dc.contributor.filiacion | Aldunate Caramori Fabián, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.contributor.filiacion | Echeverría Chagas Natalia, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.contributor.filiacion | Chiodi Daniela, Universidad de la República (Uruguay). Facultad de Medicina. | - |
dc.contributor.filiacion | López Pablo, Universidad de la República (Uruguay). Facultad de Medicina. | - |
dc.contributor.filiacion | Sánchez-Cicerón Adriana, Universidad de la República (Uruguay). Facultad de Medicina. | - |
dc.contributor.filiacion | Soñora Martín, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.contributor.filiacion | Cristina Juan, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.contributor.filiacion | Moratorio Gonzalo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.contributor.filiacion | Hernández Nelia, Universidad de la República (Uruguay). Facultad de Medicina. | - |
dc.contributor.filiacion | Moreno Karlen María del Pilar, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares. | - |
dc.rights.licence | Licencia Creative Commons Atribución (CC - By 4.0) | es |
dc.identifier.doi | 10.1186/s12879-021-06080-0 | - |
Aparece en las colecciones: | Publicaciones académicas y científicas - Facultad de Ciencias |
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