| 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 |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Hiroshima University |
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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)
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| 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)
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| 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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