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Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed

We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simepre...

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Autores principales: Yoshida, Kanako, Hai, Hoang, Tamori, Akihiro, Teranishi, Yuga, Kozuka, Ritsuzo, Motoyama, Hiroyuki, Kawamura, Etsushi, Hagihara, Atsushi, Uchida-Kobayashi, Sawako, Morikawa, Hiroyasu, Enomoto, Masaru, Murakami, Yoshiki, Kawada, Norifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454875/
https://www.ncbi.nlm.nih.gov/pubmed/28467359
http://dx.doi.org/10.3390/ijms18050962
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author Yoshida, Kanako
Hai, Hoang
Tamori, Akihiro
Teranishi, Yuga
Kozuka, Ritsuzo
Motoyama, Hiroyuki
Kawamura, Etsushi
Hagihara, Atsushi
Uchida-Kobayashi, Sawako
Morikawa, Hiroyasu
Enomoto, Masaru
Murakami, Yoshiki
Kawada, Norifumi
author_facet Yoshida, Kanako
Hai, Hoang
Tamori, Akihiro
Teranishi, Yuga
Kozuka, Ritsuzo
Motoyama, Hiroyuki
Kawamura, Etsushi
Hagihara, Atsushi
Uchida-Kobayashi, Sawako
Morikawa, Hiroyasu
Enomoto, Masaru
Murakami, Yoshiki
Kawada, Norifumi
author_sort Yoshida, Kanako
collection PubMed
description We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, p < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up.
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spelling pubmed-54548752017-06-08 Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed Yoshida, Kanako Hai, Hoang Tamori, Akihiro Teranishi, Yuga Kozuka, Ritsuzo Motoyama, Hiroyuki Kawamura, Etsushi Hagihara, Atsushi Uchida-Kobayashi, Sawako Morikawa, Hiroyasu Enomoto, Masaru Murakami, Yoshiki Kawada, Norifumi Int J Mol Sci Article We evaluated the transition of dominant resistance-associated substitutions (RASs) in hepatitis C virus during long-term follow-up after the failure of DAAs (direct acting antivirals)-based therapy. RASs in non-structure (NS)3/4A, NS5A, NS5B, and deletions in NS5A from 20 patients who failed simeprevir/pegylated-interferon/ribavirin (SMV/PEG-IFN/RBV) and 25 patients who failed daclatasvir/asunaprevir (DCV/ASV) treatment were examined by direct sequencing. With respect to SMV/PEG-IFN/RBV treatment, RAS was detected at D168 in NS3/4A but not detected in NS5A and NS5B at treatment failure in 16 of 20 patients. During the median follow-up period of 64 weeks, the RAS at D168 became less dominant in 9 of 16 patients. Among 25 DCV/ASV failures, RASs at D168, L31, and Y93 were found in 57.1%, 72.2%, and 76.9%, respectively. NS5A deletions were detected in 3 of 10 patients treated previously with SMV/PEG-IFN/RBV. The number of RASs in the breakthrough patients exceeded that in relapsers (mean 3.9 vs. 2.7, p < 0.05). RAS at D168 in NS3/4A became less dominant in 6 of 15 patients within 80 weeks. Y93H emerged at the time of relapse, then decreased gradually by 99% at 130 weeks post-treatment. Emerged RASs were associated with the clinical course of treatment and could not be detected during longer follow-up. MDPI 2017-05-03 /pmc/articles/PMC5454875/ /pubmed/28467359 http://dx.doi.org/10.3390/ijms18050962 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoshida, Kanako
Hai, Hoang
Tamori, Akihiro
Teranishi, Yuga
Kozuka, Ritsuzo
Motoyama, Hiroyuki
Kawamura, Etsushi
Hagihara, Atsushi
Uchida-Kobayashi, Sawako
Morikawa, Hiroyasu
Enomoto, Masaru
Murakami, Yoshiki
Kawada, Norifumi
Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title_full Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title_fullStr Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title_full_unstemmed Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title_short Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed
title_sort long-term follow-up of resistance-associated substitutions in hepatitis c virus in patients in which direct acting antiviral-based therapy failed
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454875/
https://www.ncbi.nlm.nih.gov/pubmed/28467359
http://dx.doi.org/10.3390/ijms18050962
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