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Basic Characteristics of Mutations
|
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Mutation Site
|
Y93H |
|
Mutation Site Sentence
|
One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10;retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. |
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Mutation Level
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Amino acid level |
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Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS5A |
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Standardized Encoding Gene
|
NS5A
|
|
Genotype/Subtype
|
1b |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Hepatitis C, Chronic
Liver Cirrhosis
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
sofosbuvir;ledipasvir |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
29435197
|
|
Title
|
Successful retreatment with sofosbuvir plus ledipasvir for cirrhotic patients with hepatitis C virus genotype 1b, who discontinued the prior treatment with asunaprevir plus daclatasvir: A case series and review of the literature
|
|
Author
|
Haga Y,Kanda T,Yasui S,Nakamura M,Ooka Y,Takahashi K,Wu S,Nakamoto S,Arai M,Chiba T,Maruyama H,Yokosuka O,Takada N,Moriyama M,Imazeki F,Kato N
|
|
Journal
|
Oncotarget
|
|
Journal Info
|
2017 Dec 29;9(4):5509-5513
|
|
Abstract
|
BACKGROUND: Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only approximately 70% SVR rates. CASE SUMMARY: Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. CONCLUSION: Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment.
|
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Sequence Data
|
-
|
|
|