The relationship between the efficacy and the prevalence of the mutant virus for the novel anti-viral drugs for hepatitis C
Project/Area Number |
25460994
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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 | Osaka University |
Principal Investigator |
hiramatsu naoki 大阪大学, 医学(系)研究科(研究院), 准教授 (30362700)
|
Co-Investigator(Kenkyū-buntansha) |
OZE tsugiko 大阪大学, 大学院医学系研究科, 寄附講座助教 (30623582)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 薬剤耐性変異 / C型肝炎 / DAA治療 / HCV遺伝子多型 / 次世代シークエンサー / シメプレビル / Deep sequence法 |
Outline of Final Research Achievements |
Factors associated with the treatment effect,including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy. The SVR rate was 50% (10/20,PPS).Ultra-deep sequencing at the start of SMV-based therapy revealed that TVR-resistant variants were detected in 6 patients (29%),and no variants at position 168 were observed. Cross-resistant variants between TVR and SMV were detected in only one patient(SVR).Higher SVRs for SMV-based therapy were attained in relapsers to prior Peg-IFN plus RBV therapy (relapsers 100% vs non-responders 20%, p = 0.007). In this study, ultra-deep sequencing analysis revealed that TVR and/or SMV-resistant variants may have no influence on the effect of SMV-based therapy after failure of TVR-based therapy. Relapsers to previous Peg-IFN/RBV therapy would be a good candidate for retreatment with SMV-based triple therapy.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Significance of liver stiffness measurement by acoustic radiation force impulse (ARFI) among hepatitis C patients.2014
Author(s)
Yamada R, Hiramatsu N, Oze T, Morishita N, Harada N, Miyazaki M, Yakushijin T, Miyagi T, Yoshida Y, Tatsumi T, Kanto T, Hayashi N, Takehara T.
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Journal Title
J Med Virol.
Volume: 86
Issue: 2
Pages: 241-7
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Risk factors for hepatocellular carcinoma in hepatitis C patients with normal ALT treated with pegylated interferon and ribavirin2014
Author(s)
Harada N, Hiramatsu N, Oze T, Morishita N, Yamada R, Hikita H, Miyazaki M, Yakushijin T, Miyagi T, Yoshida Y, Tatsumi T, Kanto A, Kasahara A, Oshita M, Mita E, Hagiwara H, Inui Y, Katayama K, Shinji Tamura, Yoshihara H, Imai Y, Inoue A, Hayashi N, Takehara T
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Journal Title
J Viral Hepat
Volume: 21
Issue: 5
Pages: 357-365
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Human blood dendritic cell antigen 3 (BDCA3)(+) dendritic cells are a potent producer of interferon-λ in response to hepatitis C virus2013
Author(s)
Yoshio S, Kanto T, Kuroda S, Matsubara T, Higashitani K, Kakita N, Ishida H, Hiramatsu N, Nagano H, Sugiyama M, Murata K, Fukuhara T, Matsuura Y, Hayashi N, Mizokami M, Takehara T
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Journal Title
Hepatology
Volume: 57
Issue: 5
Pages: 1705-15
DOI
Related Report
Peer Reviewed
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[Journal Article] The combination therapy of α-galactosylceramide and 5-fluorouracil showed antitumor effect synergistically against liver tumor in mice2013
Author(s)
Aketa H, Tatsumi T, Kohga K, Tsunematsu H, Aono S, Shimizu S, Kodama T, Nawa T, Shigekawa M, Hikita H, Sakamori R, Hosui A, Miyagi T, Hiramatsu N, Kanto T, Hayashi N, Takehara T
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Journal Title
Int J Cancer
Volume: 133
Issue: 5
Pages: 1126-34
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum Fucosylated Haptoglobin as a Novel Diagnostic Biomarker for Predicting Hepatocyte Ballooning and Nonalcoholic Steatohepatitis.2013
Author(s)
Kamada Y, Akita M, Takeda Y, Yamada S, Fujii H, Sawai Y, Doi Y, Asazawa H, Nakayama K, Mizutani K, Fujii H, Yakushijin T, Miyazaki M, Ezaki H, Hiramatsu N, Yoshida Y, Kiso S, Imai Y, Kawada N, Takehara T, Miyoshi E.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Valine, the branched-chain amino acid, suppresses hepatitis C virus RNA replication but promotes infectious particle formation2013
Author(s)
Ishida H, Kato T, Takehana K, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T
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Journal Title
Biochem Biophys Res Commun
Volume: 437
Issue: 1
Pages: 127-33
DOI
Related Report
Peer Reviewed
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[Journal Article] Carbamazepine promotes liver regeneration and survival in mice.2013
Author(s)
Kawaguchi T, Kodama T, Hikita H, Tanaka S, Shigekawa M, Nawa T, Shimizu S, Li W, Miyagi T, Hiramatsu N, Tatsumi T, Takehara T.
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Journal Title
J Hepatol.
Volume: 59
Issue: 6
Pages: 1239-1245
DOI
Related Report
Peer Reviewed
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[Journal Article] The Bcl-2 homology 3 (BH3)-only proteins Bim and Bid are functionally active and restrained by anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) family proteins in healthy liver.2013
Author(s)
[1] Kodama T, Hikita H, Kawaguchi T, Saito Y, Tanaka S, Shigekawa M, Shimizu S, Li W, Miyagi T, Kanto T, Hiramatsu N, Tatsumi T, Takehara T.
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Journal Title
J. Biol. Chem.
Volume: 288
Issue: 42
Pages: 30009-30018
DOI
Related Report
Peer Reviewed
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