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

 Kyung-Ah Kim  ;  Sejoon Lee  ;  Hye Jung Park  ;  Eun Sun Jang  ;  Youn Jae Lee  ;  Sung Bum Cho  ;  Young Suk Kim  ;  In Hee Kim  ;  Byung Seok Lee  ;  Woo Jin Chung  ;  Sang Hoon Ahn  ;  Seungtaek Kim  ;  Sook Hyang Jeong 
 CLINICAL AND MOLECULAR HEPATOLOGY, Vol.29(2) : 496-509, 2023-04 
Journal Title
Issue Date
Antiviral Agents / therapeutic use ; Cohort Studies ; Drug Resistance, Viral / genetics ; Drug Therapy, Combination ; Genotype ; Hepacivirus / genetics ; Hepatitis C* / drug therapy ; Hepatitis C, Chronic* / drug therapy ; High-Throughput Nucleotide Sequencing ; Humans ; Ribavirin / therapeutic use ; Sofosbuvir / therapeutic use ; Viral Nonstructural Proteins / genetics
Drug resistance , viral ; Genotype ; Hepatitis C virus ; Next-generation sequencing
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
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