Journalartikel

Jahr der Veröffentlichung: 2024

Zeitschrift: JHEP Reports

Bandnummer: 6

Heftnummer: 7

eISSN: 2589-5559

Open Access Status: Gold

DOI Link: https://doi.org/10.1016/j.jhepr.2024.101072

Verlag: Elsevier

Abstract: 
Background 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 ef ficacy 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 ef ficacies 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 modi fied 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 speci fic 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. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Harvard-Zitierstil: Dietz, J., Graf, C., Berg, C., Port, K., Deterding, K., Buggisch, P., et al. (2024) Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients, JHEP Reports, 6(7), Article 101072. https://doi.org/10.1016/j.jhepr.2024.101072

APA-Zitierstil: Dietz, J., Graf, C., Berg, C., Port, K., Deterding, K., Buggisch, P., Peiffer, K., Vermehren, J., Dultz, G., Geier, A., Reiter, F., Bruns, T., Schattenberg, J., Durmashkina, E., Gustot, T., Moreno, C., Trauth, J., Discher, T., Fischer, J., ...Sarrazin, C. (2024). Rare HCV subtypes and retreatment outcomes in a cohort of European DAA-experienced patients. JHEP Reports. 6(7), Article 101072. https://doi.org/10.1016/j.jhepr.2024.101072