Publicação
Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort
| Resumo: | Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA). Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping. Study design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated. Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15)). Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping. |
|---|---|
| Autores principais: | Christensen, Kasper T. |
| Outros Autores: | Pierard, Florian; Beuselinck, Kurt; Bonsall, David; Bowden, Rory; Lagrou, Katrien; Nevens, Frederik; Schrooten, Yoeri; Simmonds, Peter; Vandamme, Anne Mieke; Van Wijngaerden, Eric; Dierckx, Tim; Cuypers, Lize; Van Laethem, Kristel |
| Assunto: | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1868983326256136192 |
|---|---|
| author | Christensen, Kasper T. |
| author2 | Pierard, Florian Beuselinck, Kurt Bonsall, David Bowden, Rory Lagrou, Katrien Nevens, Frederik Schrooten, Yoeri Simmonds, Peter Vandamme, Anne Mieke Van Wijngaerden, Eric Dierckx, Tim Cuypers, Lize Van Laethem, Kristel |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Christensen, Kasper T. Pierard, Florian Beuselinck, Kurt Bonsall, David Bowden, Rory Lagrou, Katrien Nevens, Frederik Schrooten, Yoeri Simmonds, Peter Vandamme, Anne Mieke Van Wijngaerden, Eric Dierckx, Tim Cuypers, Lize Van Laethem, Kristel |
| author_role | author |
| contributor_name_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) TB, HIV and opportunistic diseases and pathogens (THOP) Universidade NOVA de Lisboa Elsevier Science B.V., Amsterdam. RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Christensen, Kasper T.\"},{\"Person.name\":\"Pierard, Florian\"},{\"Person.name\":\"Beuselinck, Kurt\"},{\"Person.name\":\"Bonsall, David\"},{\"Person.name\":\"Bowden, Rory\"},{\"Person.name\":\"Lagrou, Katrien\"},{\"Person.name\":\"Nevens, Frederik\"},{\"Person.name\":\"Schrooten, Yoeri\"},{\"Person.name\":\"Simmonds, Peter\"},{\"Person.name\":\"Vandamme, Anne Mieke\"},{\"Person.name\":\"Van Wijngaerden, Eric\"},{\"Person.name\":\"Dierckx, Tim\"},{\"Person.name\":\"Cuypers, Lize\"},{\"Person.name\":\"Van Laethem, Kristel\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) TB, HIV and opportunistic diseases and pathogens (THOP) Universidade NOVA de Lisboa Elsevier Science B.V., Amsterdam. RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Christensen, Kasper T. Pierard, Florian Beuselinck, Kurt Bonsall, David Bowden, Rory Lagrou, Katrien Nevens, Frederik Schrooten, Yoeri Simmonds, Peter Vandamme, Anne Mieke Van Wijngaerden, Eric Dierckx, Tim Cuypers, Lize Van Laethem, Kristel |
| datacite.date.Accepted.fl_str_mv | 2022-10-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2023-01-18T22:17:29Z |
| datacite.date.embargoed.fl_str_mv | 2023-01-18T22:17:29Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| datacite.titles.title.fl_str_mv | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| dc.contributor.none.fl_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) TB, HIV and opportunistic diseases and pathogens (THOP) Universidade NOVA de Lisboa Elsevier Science B.V., Amsterdam. RUN |
| dc.creator.none.fl_str_mv | Christensen, Kasper T. Pierard, Florian Beuselinck, Kurt Bonsall, David Bowden, Rory Lagrou, Katrien Nevens, Frederik Schrooten, Yoeri Simmonds, Peter Vandamme, Anne Mieke Van Wijngaerden, Eric Dierckx, Tim Cuypers, Lize Van Laethem, Kristel |
| dc.date.Accepted.fl_str_mv | 2022-10-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2023-01-18T22:17:29Z |
| dc.date.embargoed.fl_str_mv | 2023-01-18T22:17:29Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/147814 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| dc.title.fl_str_mv | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA). Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping. Study design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated. Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15)). Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/c60d7ba3-ee90-4199-b406-a6f26bede14c/download |
| id | run_b34a5dfd82914e06c25f45fcfbb92cee |
| identifier.url.fl_str_mv | http://hdl.handle.net/10362/147814 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/147814 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Christensen, Kasper T. Pierard, Florian Beuselinck, Kurt Bonsall, David Bowden, Rory Lagrou, Katrien Nevens, Frederik Schrooten, Yoeri Simmonds, Peter Vandamme, Anne Mieke Van Wijngaerden, Eric Dierckx, Tim Cuypers, Lize Van Laethem, Kristel |
| publishDate | 2022 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
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| spelling | engenBackground: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA). Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping. Study design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated. Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15)). Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping.application/pdfenFull-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohortChristensen, Kasper T.Pierard, FlorianBeuselinck, KurtBonsall, DavidBowden, RoryLagrou, KatrienNevens, FrederikSchrooten, YoeriSimmonds, PeterVandamme, Anne MiekeVan Wijngaerden, EricDierckx, TimCuypers, LizeVan Laethem, KristelInstituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)TB, HIV and opportunistic diseases and pathogens (THOP)Universidade NOVA de LisboaElsevier Science B.V., Amsterdam.HostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf1386-6532URNIsPartOfPURE: 50787197URNIsPartOfPURE UUID: 9ae15e77-6372-4595-8d94-628b1e71ac27URNIsPartOfScopus: 85135959966URNIsPartOfPubMed: 35981443DOIIsPartOf10.1016/j.jcv.2022.1052522023-01-18T22:17:29Z2022-102022-10-01T00:00:00ZHandlehttp://hdl.handle.net/10362/147814http://purl.org/coar/access_right/c_abf2open accessAntiviral resistanceFull genomeHepatitis C virusLiPANext-generation sequencingTreatment failureQR355 VirologyR MedicineVirologyInfectious DiseasesApplied Microbiology and BiotechnologySDG 3 - Good Health and Well-beingSDG 9 - Industry, Innovation, and Infrastructure1967295 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/c60d7ba3-ee90-4199-b406-a6f26bede14c/download |
| spellingShingle | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort Christensen, Kasper T. Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| status | SINGLETON |
| subject.fl_str_mv | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| title | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| title_full | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| title_fullStr | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| title_full_unstemmed | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| title_short | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| title_sort | Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort |
| topic | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| topic_facet | Antiviral resistance Full genome Hepatitis C virus LiPA Next-generation sequencing Treatment failure QR355 Virology R Medicine Virology Infectious Diseases Applied Microbiology and Biotechnology SDG 3 - Good Health and Well-being SDG 9 - Industry, Innovation, and Infrastructure |
| url | http://hdl.handle.net/10362/147814 |
| visible | 1 |