Publication:
Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients.

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dc.contributor.authorDietz, Julia
dc.contributor.authorGraf, Christiana
dc.contributor.authorBerg, Christoph P
dc.contributor.authorPort, Kerstin
dc.contributor.authorDeterding, Katja
dc.contributor.authorBuggisch, Peter
dc.contributor.authorPeiffer, Kai-Henrik
dc.contributor.authorVermehren, Johannes
dc.contributor.authorDultz, Georg
dc.contributor.authorGeier, Andreas
dc.contributor.authorReiter, Florian P
dc.contributor.authorBruns, Tony
dc.contributor.authorSchattenberg, Jörn M
dc.contributor.authorDurmashkina, Elena
dc.contributor.authorGustot, Thierry
dc.contributor.authorMoreno, Christophe
dc.contributor.authorTrauth, Janina
dc.contributor.authorDischer, Thomas
dc.contributor.authorFischer, Janett
dc.contributor.authorBerg, Thomas
dc.contributor.authorKremer, Andreas E
dc.contributor.authorMüllhaupt, Beat
dc.contributor.authorZeuzem, Stefan
dc.contributor.authorSarrazin, Christoph
dc.date.accessioned2024-12-03T07:04:32Z
dc.date.available2024-12-03T07:04:32Z
dc.date.issued2024-07
dc.descriptionKollektivautorenschaft: Forschungsgruppe "European HCV Resistance Study Group", Autor UniBE: Nasser Semmo, Universitätsklinik für Viszerale Chirurgie und Medizin
dc.description.abstractBackground And Aims Data on the prevalence and characteristics of so-called rare HCV genotypes (GTs) in larger cohorts is limited. This study investigates the frequency of rare GT and resistance-associated substitutions and the efficacy of retreatment in a European cohort.Methods A total of 129 patients with rare GT1-6 were included from the European resistance database. NS3, NS5A, and NS5B were sequenced and clinical parameters and retreatment efficacies were collected retrospectively.Results Overall 1.5% (69/4,656) of direct-acting antiviral (DAA)-naive and 4.4% (60/1,376) of DAA-failure patients were infected with rare GT. Although rare GTs were almost equally distributed throughout GT1-6 in DAA-naive patients, we detected mainly rare GT4 (47%, 28/60 GT4; of these n = 17, subtype 4r) and GT3 (25%, 15/60 GT3, of these n = 8, subtype 3b) among DAA-failures. A total of 62% (37/60) of DAA failures had not responded to first-generation regimes and the majority was infected with rare GT4 (57%, 21/37). In contrast, among patients with failure to pangenotypic DAA regimens (38%, 23/60), infections with rare GT3 were overrepresented (57%, 13/23). Although NS5A RASs were uncommon in rare GT2, GT5a, and GT6, we observed combined RASs in rare GT1, GT3, and GT4 at positions 28, 30, 31, which can be considered as inherent. DAA failures with completed follow-up of retreatment, achieved a high SVR rate (94%, 45/48 modified intention-to-treat analysis; 92%, 45/49 intention-to-treat). Three patients with GT4f, 4r, or 3b, respectively, had virological treatment failure.Conclusions In this European cohort, rare HCV GT were uncommon. Accumulation of specific rare GT in DAA-failure patients suggests reduced antiviral activities of DAA regimens. The limited global availability of pangenotypic regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.Impact And Implications Data on the prevalence and characteristics of rare HCV genotypes (GT) in larger cohorts are still scarce. This study found low rates of rare HCV GTs among European HCV-infected patients. In direct-acting antiviral (DAA)-failure patients, rare GT3 subtypes accumulated after pangenotypic DAA treatment and rare GT4 after first generation DAA failure and viral resistance was detected at NS5A positions 28, 30, and 31. The limited global availability of pangenotypic DAA regimens for first line therapy as well as multiple targeted regimens for retreatment could result in HCV elimination targets being delayed.
dc.description.sponsorshipClinic of Visceral Surgery and Medicine, Hepatology
dc.identifier.doi10.48620/77077
dc.identifier.pmid39006503
dc.identifier.publisherDOI10.1016/j.jhepr.2024.101072
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/191063
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofJHEP Reports
dc.relation.issn2589-5559
dc.subjectDirect-acting antivirals
dc.subjectHepatitis C Virus
dc.subjectrare HCV genotypes
dc.subjectresistance-associated substitutions
dc.subjecttreatment response
dc.titleRare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients.
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.issue7
oaire.citation.startPage101072
oaire.citation.volume6
unibe.additional.sponsorshipClinic of Visceral Surgery and Medicine, Hepatology
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unibe.subtype.articlejournal

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