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Background and Aim: Although interferon-free antiviral treatment is improved sustained virological response (SVR) rate of hepatitis C virus (HCV), pre-existing NS5A/NS5B resistance associated variants (RAVs) may affect the efficiency of some HCV regimens. The aim of study is to investigate whether the NS5A/NS5B RAVs interact with clinical characteristics and response to 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir (SOF) combined with the NS5A inhibitor ledipasvir (LDV) for genotype (GT)-1b infection. Methods:Three hundred sixteen Japanese patients with HCV GT-1b (mean Age [ys]:67, male [%]:32, treatment na?ve [%]:53 cirrhosis [%]:30, and hepatocellular carcinoma (HCC) [%]:10) were examined NS5A/NS5B RAVs by direct sequence. NS5A RAVs included L31M/I/V/F and Y93H, and NS5B RAVs included S282T and C316N. The frequency of the RAVs was examined the association with clinical characteristics, such as age, sex, na?ve/experienced, HCVRNA, fibrosis, and hepatocellular carcinoma (HCC). Fibrosis was evaluated by Fibroscan and Mac-2 binding protein glycogen isomer. Among these patients, 59 patients (23%) who received LDV (90 mg)/SOF (400 mg) for 12 weeks were analyzed the association of pre-treatment NS5A/NS5B RAVs with treatment outcome. Results: Distribution of NS5A RAVs existed 5% for L31 and 23% for Y93. Double mutations in NS5A were detected only 5 patients (1.5%). Distribution of NS5B RAVs existed 48% for C316; however there were no detection for S282 mutation. No association of these RAVs distribution with clinical characteristics.Fifty nine patients with receiving SOF/LDV were detected 23% for NS5A RAVs, 48% for C316N, and 11% for NS5A RAVs with C316N and All 59 patients achieved SVR (100%).Conclusions:Although pre-treatment NS5A and NS5B RAVs inJapanese patients with infected HCV GT-1b exist about 25% and 50% respectively, presence of single RAVs, and NS5A RAVs with C316N in NS5B are less association with clinical characteristics, and treatment outcome of SOF/LDV. 文自 Takeshi Watabe, Masaaki Korenaga, Masaya Sugiyama, Erina Kumagai, Misuzu Ueyama, Yoshihiko Aoki, Yoko Yamagiwa, Keiko Korenaga, Masatoshi Imamura, Kazumoto Murata, Naohiko Masaki, Tatsuya Kanto, Masashi Mizokami; The research center for hepatitis and Immunology, National Center of Global Health and Medicine (NCGM) at Kohnodai, Ichikawa, Japan |
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