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Next-generation sequencing analysis of hepatitis C virus resistance–associated substitutions in direct-acting antiviral failure in South Korea

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Author(s)
Kyung-Ah KimSejoon LeeHye Jung ParkEun Sun JangYoun Jae LeeSung Bum ChoYoung Suk KimIn Hee KimByung Seok LeeWoo Jin ChungSang Hoon AhnSeungtaek KimSook Hyang Jeong
Keimyung Author(s)
Chung, Woo Jin
Department
Dept. of Internal Medicine (내과학)
Journal Title
Clin Mol Hepatol
Issued Date
2023
Volume
29
Issue
2
Keyword
Hepatitis C virusGenotypeDrug resistance, viralNext-generation sequencing
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.
Keimyung Author(s)(Kor)
정우진
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2287-285X
Source
https://www.e-cmh.org/journal/view.php?doi=10.3350/cmh.2022.0345
DOI
10.3350/cmh.2022.0345
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44890
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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