Mechanism of emergence of hepatitis C virus with resistance-associated substitution after liver transplantation
| Project/Area Number |
17K09420
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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 | Kobe University (2019)
Kyoto University (2017-2018) |
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Principal Investigator |
Ueda Yoshihide 神戸大学, 医学研究科, 特命教授 (90378662)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | C型肝炎 / 肝移植 / direct acting antiviral / 耐性変異 / インターフェロンフリー治療 |
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| Outline of Final Research Achievements |
Efficacy and safety of 12-week-regimen of sofosbuvir and ledipasvir, and 8- or 12-week regimen of glecaprevir and pibrentasvir were efficacious and safe in patients with recurrent hepatitis C after liver transplantation in our institution and in Japanese multicenter analysis. Diversity of HCV RNA in post-liver transplant and non-liver transplant patients were analyzed by using third-generation sequencing technique. We revealed that multi-drug resistant HCV clones at treatment failure originated from a subpopulation of pre-existing HCV with resistance-associated substitution, and those HCV were selected for and became dominant with the acquisition of multiple resistance-associated substitutions.
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| Academic Significance and Societal Importance of the Research Achievements |
C型肝炎ウイルス（HCV）による肝硬変・肝癌症例に対して肝移植が行われた場合には、ほぼ全例で移植後にC型肝炎が再発すること、再発後の進行が速いこと、抗HCV治療の効果が低く副作用が多いことから、肝移植後の長期生存率が低いことが明らかになっていた。本研究では、新しい抗HCV治療が肝移植後C型肝炎に対しても効果的で安全であることを明らかにした。さらに、治療不成功の原因となる薬剤耐性ウイルス出現の機序を、新しい遺伝子解析技術を用いて明らかにした。今後、肝移植後の生存率の向上が期待できる。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Single-molecular real-time deep sequencing reveals the dynamics of multidrug resistant haplotypes and structural variations in the hepatitis C virus genome.2020
Author(s)
Yamashita T, Takeda H, Takai A, Arasawa S, Nakamura F, Mashimo Y, Hozan M, Ohtsuru S, Seno H,Ueda Y, Sekine A
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Journal Title
Sci. Rep,
Volume: 10
Issue: 1
Pages: 2651-2651
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Efficacy and safety of glecaprevir and pibrentasvir treatment for 8 or 12 weeks in patients with recurrent hepatitis C after liver transplantation: A Japanese multicenter experience.2019
Author(s)
Ueda Y, Kobayashi T, Ikegami T, Miuma S, Mizuno S, Akamatsu N, Tkaki A, Ishigami M, Takatsuki M, Sugawara Y, Maehara Y, Uemoto S, Seno H.
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Journal Title
J Gastroenterol.
Volume: 印刷中
Issue: 7
Pages: 660-666
DOI
Related Report
Peer Reviewed
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[Journal Article] Impact of Donor Age on Recipient Survival in Adult-to-adult Living-donor Liver Transplantation.2017
Author(s)
Kubota T, Hata K, Sozu T, Ueda Y, Hirao H, Okamura Y, Tamaki I, Yoshikawa J, Kusakabe J, Uemoto S, et al.
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Journal Title
Annals of Surgery
Volume: In Press
Issue: 6
Pages: 1126-1133
DOI
Related Report
Peer Reviewed
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[Presentation] Treatment with sofosbuvir and ledipasvir without ribavirin for 12 weeks is highly effective for recurrent hepatitis C after living donor liver transplantation: a Japanese multicenter experience.2017
Author(s)
Yoshihide Ueda, Toru Ikegami, Nobuhisa Akamatsu, Akihiko Soyama, Masahiro Shinoda, Ryoichi Goto, Hideaki Okajima, Tomoharu Yoshizumi, Akinobu Taketomi, Yuko Kitagawa, Susumu Eguchi, Norihiro Kokudo, Shinji Uemoto, Yoshihiko Maehara.
Organizer
EASL The Internationala liver congress 2017
Related Report
Int'l Joint Research
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