ArticleScientific reports2017
Baseline quasispecies selection and novel mutations contribute to emerging resistance-associated substitutions in hepatitis C virus after direct-acting antiviral treatment.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan.Antimicrobial agents and chemotherapy · 2018Trial
- QoALa: A comprehensive workflow for viral quasispecies diversity comparison using long-read sequencing data.PLoS computational biology · 2026Article
- Article
- Screening of the Pandemic Response Box Library Identified CRM1/XPO1 as an Anti-Mammarenavirus Druggable Target.Viruses · 2026Article
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors.Scientific reports · 2024Article
- Direct-acting antivirals sofosbuvir and daclatasvir attenuate carbon tetrachloride-induced liver fibrosis in mice.Liver research (Beijing, China) · 2023Article
- Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture.Frontiers in microbiology · 2022Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Article
- The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors.Antiviral research · 2019Article
- Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice.Journal of gastroenterology · 2019Article
- Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus.World journal of gastroenterology · 2018Article
- Pipeline for specific subtype amplification and drug resistance detection in hepatitis C virus.BMC infectious diseases · 2018Article
- HA1077 displays synergistic activity with daclatasvir against hepatitis C virus and suppresses the emergence of NS5A resistance-associated substitutions in mice.Scientific reports · 2018Article
- Baseline hepatitis C virus resistance-associated substitutions present at frequencies lower than 15% may be clinically significant.Infection and drug resistance · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance-associated substitutions (RASs) in hepatitis C virus (HCV) appear upon failure of treatment with direct-acting antivirals (DAAs). However, their origin has not been clarified in detail. Among 11 HCV genotype 1b patients who experienced virologic failure with asunaprevir (ASV)/daclatasvir (DCV), 10 had major NS5A L31M/V-Y93H variants after treatment. L31M/V-Y93H variants were detected as a minor clone before therapy in 6 patients and were the most closely related to the post-treatment variants by phylogenetic tree analysis in 4 patients. Next, to consider the involvement of a trace amount of pre-existing variants below the detection limit, we analysed human hepatocyte chimeric mice infected with DAA-naïve patient serum. L31V-Y93H variants emerged after treatment with ledipasvir (LDV)/GS-558093 (nucleotide NS5B inhibitor) and decreased under the detection limit, but these variants were dissimilar to the L31V-Y93H variants reappearing after ASV/DCV re-treatment. Finally, to develop an infection derived from a single HCV clone, we intrahepatically injected full-genome HCV RNA (engineered based on the wild-type genotype 1b sequence) into chimeric mice. A new Y93H mutation actually occurred in this model after LDV monotherapy failure. In conclusion, post-treatment RASs appear by 2 mechanisms: the selection of pre-existing substitutions among quasispecies and the generation of novel mutations during therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.