Muñoz de Rueda, PalomaFuentes Rodríguez, José ManuelQuiles Pérez, RosaGila Medina, AnaMartín Álvarez, Ana BelénCasado Ruíz, JorgeRuíz Extremera, AngelesSalmerón, Javier2023-01-252023-01-252017http://hdl.handle.net/10668/11436To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/Chronic hepatitis CInterferon-based therapyInterferon-free therapyNS5A regionNumber of mutationsSustained virological responseAntiviral AgentsDrug Resistance, Multiple, ViralDrug Therapy, CombinationFemaleGenotypeHepacivirusHepatitis C, ChronicHumansInterferon-alphaMaleMutationPolyethylene GlycolsProspective StudiesRetrospective StudiesRibavirinSequence Analysis, RNASustained Virologic ResponseViral LoadViral Nonstructural Proteinsresearch article28740342open access10.3748/wjg.v23.i25.45382219-2840PMC5504369https://doi.org/10.3748/wjg.v23.i25.4538https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504369/pdf