Clin Mol Hepatol.
2023 Apr;29(2):496-509. 10.3350/cmh.2022.0345.
Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea
- Affiliations
-
- 1Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
- 2Department of Precision Medicine Center/Department of Pathology and Translational Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- 3Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- 4Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- 5Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
- 6Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea
- 7Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- 8Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, Korea
- 9Department of Internal Medicine, Chungnam National University Hospital, Daejoen, Korea
- 10Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
- 11Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam, Korea
- KMID: 2541438
- DOI: http://doi.org/10.3350/cmh.2022.0345
Abstract
- Background/Aims
We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea.
Methods
Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS.
Results
RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate.
Conclusions
NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.
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