|
Basic Characteristics of Mutations
|
|
Mutation Site
|
Y93H |
|
Mutation Site Sentence
|
Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS5A |
|
Standardized Encoding Gene
|
NS5A
|
|
Genotype/Subtype
|
1b |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Hepatitis C, Chronic
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
ledipasvir |
|
Location
|
Japan |
|
Literature Information
|
|
PMID
|
26208695
|
|
Title
|
Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice
|
|
Author
|
Kai Y,Hikita H,Tatsumi T,Nakabori T,Saito Y,Morishita N,Tanaka S,Nawa T,Oze T,Sakamori R,Yakushijin T,Hiramatsu N,Suemizu H,Takehara T
|
|
Journal
|
Journal of gastroenterology
|
|
Journal Info
|
2015 Nov;50(11):1145-51
|
|
Abstract
|
BACKGROUND: Resistance-associated variants (RAVs) emerge at multiple positions spanning hepatitis C virus (HCV) NS3/4A and NS5A regions upon failure of asunaprevir/daclatasvir combination therapy. It has not been determined whether the emergence of such RAVs have an impact on re-treatment by a combination of ledipasvir and sofosbuvir, a potent regimen for HCV genotype 1 infection. METHODS: TK-NOG human hepatocyte chimeric mice were inoculated with sera from a patient with treatment failure of asunaprevir/daclatasvir therapy. RESULTS: They developed persistent HCV infection with triple variants of NS3/4A D168V, NS5A L31V plus Y93H. Administration of ledipasvir/GS-558093 (a NS5B nucleotide analog) in these mice failed to achieve end-of-treatment response or sustained virologic response, which was in sharp contrast to the results in mice with wild-type virus infection. The administration of telaprevir/GS-558093 successfully achieved it in those mice. CONCLUSIONS: Treatment failure with asunaprevir/daclatasvir may limit further treatment options. This population may represent a growing unmet medical need.
|
|
Sequence Data
|
-
|