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Scand J Gastroenterol. 2019 Aug;54(8):1042-1050. doi: 10.1080/00365521.2019.1652846. Epub 2019 Aug 19.

Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway.

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Department of Medical Sciences, Section of Clinical Microbiology, Uppsala University , Uppsala , Sweden.
Gastroenterology and Nutrition Research Group, Department of Clinical Medicine, UiT the Arctic University of Norway , Tromsø , Norway.
Department of Medicine, University Hospital of North Norway , Tromsø , Norway.
HBIGS, University of Heidelberg , Heidelberg , Germany.
Institute of Biology II, University of Freiburg , Freiburg , Germany.
Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, Örebro University , Örebro , Sweden.
Department of Infectious Diseases, Falun Hospital , Falun , Sweden.
Nordlandssykehuset Bodø, Department of Clinical Medicine (IKM), UiT the Artic University of Tromsø , Tromsø , Norway.
Department of Infectious Diseases, Karolinska University Hospital/Karolinska Institutet , Stockholm , Sweden.
Research Group for Host-Microbe Interactions, Department of Medical Biology, UiT the Arctic University of Norway , Tromsø , Norway.
Department of Microbiology and Infection Control, University Hospital of North Norway , Tromsø , Norway.
Department of Medical Sciences, Section of Infectious Diseases, Uppsala University Hospital , Uppsala , Sweden.


Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017. Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment. Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment. Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.


Baseline resistance; NS5A; Y93H; hepatitis C virus; resistance-associated substitution; sustained virologic response

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