Journal article

Authors list: Dietz, Julia; Muellhaupt, Beat; Buggisch, Peter; Graf, Christiana; Peiffer, Kai-Henrik; Matschenz, Katrin; Schattenberg, Joern M.; Antoni, Christoph; Mauss, Stefan; Niederau, Claus; Discher, Thomas; Trauth, Janina; Dultz, Georg; Wiesch, Julian Schulze zur; Piecha, Felix; Klinker, Hartwig; Mueller, Tobias; Berg, Thomas; Neumann-Haefelin, Christoph; Berg, Christoph P.; Zeuzem, Stefan; Sarrazin, Christoph

Publication year: 2023

Pages: 57-66

Journal: Journal of Hepatology

Volume number: 78

Issue number: 1

ISSN: 0168-8278

eISSN: 1600-0641

DOI Link: https://doi.org/10.1016/j.jhep.2022.08.016

Publisher: Elsevier

Abstract: 
Background & Aims: Data on the long-term persistence of HCV resistance-associated substitutions (RASs) after treatment with direct-acting antivirals (DAAs) are limited. This study evaluated the persistence of NS3, NS5A, and NS5B RASs for up to 5 years after the end of treatment (EOT).Methods: We included samples from 678 individuals with an HCV genotype (GT) 1 or 3 infection and virologic DAA treatment failure collected in the European Resistance Database. NS3, NS5A, and NS5B were sequenced, and clinical parameters were evaluated. Results: A total of 242 individuals with HCV GT1a (36%), 237 with GT1b (35%), and 199 (29%) with GT3 and a DAA failure were included. After protease inhibitor failure, the frequencies of NS3 RASs were 40-90% after the EOT. NS3 RASs disappeared rapidly in GT1b and GT3 after follow-up month 3 but were stable (>-60%) in GT1a owing to Q80K. The SOF-resistant NS5B RAS S282T was only found in individuals with GT3a. Non-nucleoside NS5B RASs were frequent in GT1 (56-80%) and decreased to 30% in GT1a but persisted in GT1b. NS5A RASs were very common in all GTs after NS5A inhibitor failure (88-95%), and even after follow-up month 24, their frequency was 65% and higher. However, RASs in GT1b had a stable course, whereas RASs in GT1a and GT3 declined slightly after follow-up month 24 (GT1a, 68%; GT1b, 95%; and GT3, 65%), mainly because of the slow decline of high-level resistant Y93H. Conclusions: We found that low-to medium-level RASs persisted, whereas high-level resistant RASs disappeared over time. Different patterns of RAS persistence according to HCV subtype could have implications for retreatment with first-generation DAAs and for global HCV elimination goals.(c) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Harvard Citation style: Dietz, J., Muellhaupt, B., Buggisch, P., Graf, C., Peiffer, K., Matschenz, K., et al. (2023) Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure, Journal of Hepatology, 78(1), pp. 57-66. https://doi.org/10.1016/j.jhep.2022.08.016

APA Citation style: Dietz, J., Muellhaupt, B., Buggisch, P., Graf, C., Peiffer, K., Matschenz, K., Schattenberg, J., Antoni, C., Mauss, S., Niederau, C., Discher, T., Trauth, J., Dultz, G., Wiesch, J., Piecha, F., Klinker, H., Mueller, T., Berg, T., Neumann-Haefelin, C., ...Sarrazin, C. (2023). Long-term persistence of HCV resistance-associated substitutions after DAA treatment failure. Journal of Hepatology. 78(1), 57-66. https://doi.org/10.1016/j.jhep.2022.08.016