Development of therapies for DAA-resistant HCV
Project/Area Number |
26461008
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Hiroshima University |
Principal Investigator |
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Research Collaborator |
Nobuhiko Hiraga 広島大学, 大学院医歯薬保健学研究院
Keiichi Kosaka 広島大学, 大学院医歯薬保健学研究院
Kan Hiromi 広島大学, 大学院医歯薬保健学研究院
Takuro Uchida 広島大学, 大学院医歯薬保健学研究院
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | C型慢性肝炎 / DAA / 薬剤耐性変異 / NS5A阻害薬 / ヒト肝細胞キメラマウス / 耐性変異 / deep sequence |
Outline of Final Research Achievements |
Direct-acting antiviral (DAA) is effective for chronic hepatitis C. However, resistant associated variants (RAVs) is one of the problems. In the present study, using chronic hepatitis C patients serum samples and HCV-infected human hepatocyte chimeric mice, we clarified 1) Genotype 1 HCV-infected patients with either protease inhibitor or NS5A inhibitor RAVs are likely to fail to daclatasvir plus asunaprevir treatment. 2) While protease inhibitor RAVs that emerged during therapy gradually decreases and became undetectable by deep sequencing analysis, emerged NS5A inhibitor RAVs tends to long-term persist in the absence of the drug. 3) The virological response to daclatasvir plus asunaprevir treatment was low in patients with simeprevir treatment failure. Protease inhibitor resistance remains even after disappearance of mutant strains by deep sequencing.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Protease inhibitor resistance remains even after mutant strains become undetectable using deep sequencing2016
Author(s)
Kan H, Imamura M, Uchida T, Hiraga N, Hayes CN, Tsuge M, Abe H, Aikata H, Makokha GN, Chowdhury S, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
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Journal Title
Journal of Infectious Disease
Volume: 214
Issue: 11
Pages: 1687-1694
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir andBMS-788329 combination therapy in human hepatocyte chimeric mice.2016
Author(s)
Uchida T, Hiraga N, Imamura M, Yoshimi S, Kan H, Miyaki E, Tsuge M, Abe H, Hayes CN, Aikata H, Ishida Y, Tateno C, Ellis JD, Chayama K.
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Journal Title
Virus Reserch
Volume: 213
Pages: 62-8
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Combination therapies with daclatasvir and asunaprevir on NS3-D168 mutated HCV in human hepatocyte chimeric mice2016
Author(s)
Kan H, Hiraga N, Imamura M, Hayes CN, Uchida T, Miyaki E, Tsuge M, Abe H, Aikata H, Miki D, Ochi H, Ishida Y, Tateno C, Chayama K.
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Journal Title
Antiviral Therapy
Volume: 21
Issue: 4
Pages: 307-15
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Long term persistence of NS5A inhibitor-resistant hepatitis C virus in patients who failed daclatasvir and asunaprevir therapy.2015
Author(s)
Yoshimi S, Imamura M, Murakami E, Hiraga N, Tsuge M, Kawakami Y, Aikata H, Abe H, Hayes CN, Sasaki T, Ochi H, Chayama K.
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Journal Title
J Med Virol.
Volume: 87
Issue: 11
Pages: 1913-1920
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Ultradeep sequencing study of chronic hepatitis C virus genotype 1 infection in patients treated with daclatasvir, peginterferon, and ribavirin2014
Author(s)
Murakami, E. Imamura, M. Hayes, C. N. Abe, H. Hiraga, N. Honda, Y. Ono, A. Kosaka, K. Kawaoka, T. Tsuge, M. Aikata, H. Takahashi, S. Miki, D. Ochi, H. Matsui, H. Kanai, A. Inaba, T. McPhee, F. Chayama, K.
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Journal Title
Antimicrob Agents Chemother
Volume: 58
Issue: 4
Pages: 2105-2112
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1.2014
Author(s)
Kosaka K, Imamura M, Hayes CN, Abe H, Hiraga N, Yoshimi S, Murakami E, Kawaoka T, Tsuge M, Aikata H, Miki D, Ochi H, Matsui H, Kanai A, Inaba T, Chayama K.
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Journal Title
J Viral Hepat.
Volume: 22
Issue: 2
Pages: 158-165
DOI
Related Report
Peer Reviewed / Open Access
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