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The presence of multiple NS 5A RAS s is associated with the outcome of sofosbuvir and ledipasvir therapy in NS 5A inhibitor‐naïve patients with chronic HCV genotype 1b infection in a real‐world cohort
Author(s) -
Kozuka R.,
Hai H.,
Motoyama H.,
Hagihara A.,
Fujii H.,
UchidaKobayashi S.,
Morikawa H.,
Enomoto M.,
Murakami Y.,
Kawada N.,
Tamori A.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12850
Subject(s) - ns5a , ledipasvir , sofosbuvir , medicine , gastroenterology , chronic hepatitis , hepatitis c virus , virology , virus , hepacivirus , ribavirin
Summary It is unclear whether multiple nonstructural ( NS ) 5A resistance‐associated substitutions ( RAS s) correlate with the outcome of sofosbuvir ( SOF ) and ledipasvir ( LDV ) therapy. We investigated the effects of multiple NS 5A RAS s in NS 5A inhibitor‐naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF / LDV . In 313 patients treated with SOF / LDV , we assessed the effects of multiple NS 5A RAS s on the sustained virological response ( SVR ). RAS s at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS 5A region were examined by direct sequencing. The prevalence of RAS s was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RAS s. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS , 29.8%, 45.6% and 24.6% had one, two and three or more NS 5A RAS s, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS 5A RAS s compared to those with fewer than three NS 5A RAS s (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS 5A RAS s at baseline was low in NS 5A inhibitor‐naïve patients, the presence of multiple NS 5A RAS s was associated with the effectiveness of SOF / LDV therapy.