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Deep sequencing analysis of variants resistant to the non‐structural 5 A inhibitor daclatasvir in patients with genotype 1b hepatitis C virus infection
Author(s) -
Miura Mika,
Maekawa Shinya,
Sato Mitsuaki,
Komatsu Nobutoshi,
Tatsumi Akihisa,
Takano Shinichi,
Amemiya Fumitake,
Nakayama Yasuhiro,
Inoue Taisuke,
Sakamoto Minoru,
Enomoto Nobuyuki
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12316
Subject(s) - daclatasvir , ns5a , virology , genotype , biology , hepatitis c virus , medicine , virus , gene , hepacivirus , genetics , ribavirin
Aim Daclatasvir, a non‐structural ( NS )5 A replication complex inhibitor, is a potent and promising direct antiviral agent ( DAA ) for hepatitis C virus ( HCV ), being most effective in genotype 1b infection. Although it is known that genotype 1b viruses with Y 93 H and/or L 31 M / V / F mutations have strong resistance to daclatasvir, it is not known whether there are some clinical background conditions that favor the occurrence of HCV carrying those NS 5 A mutations. Methods I n this study, we carried out deep sequencing analysis of stored sera to determine the presence and significance of daclatasvir‐resistant mutants in 110 genotype 1b HCV ‐infected patients with no previous daclatasvir treatment. Results Deep sequencing analysis revealed that the NS 5 A L 31 M / V / F and Y 93 H mutations were present in 13 (11.8%) and 34 (30.9%) of the 110 patients, respectively, and significantly more frequently than in the control plasmid. Simultaneous L 31 M / V / F and Y 93 H mutations were detected in four of the 110 patients (3.6%). When the clinical relevance of NS 5 A resistance was investigated, Y 93 H was significantly correlated with the IL 28 B major ( TT ) genotype of the host ( P = 0.042). Conclusion Y 93 H was detected frequently by deep sequencing in daclatasvir treatment‐naïve patients. Importantly, it seems that the IL 28 B status of the patients may influence the presence of Y 93 H mutations, resulting in different treatment responses to daclatasvir.