Reversible and irreversible damages of hepatocyte after DAA treatment for HCV carriers
Project/Area Number |
17K09447
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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 | National Institute of Infectious Diseases |
Principal Investigator |
Wakita Takaji 国立感染症研究所, 所長, 所長 (40280789)
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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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | HCV / HCV |
Outline of Final Research Achievements |
Development of DAA for HCV has dramatically changed its prognosis. On the other hand, persistence of liver damage after elimination of virus and HCC are problems after viral clearance. In this study, we analyzed the ultrastructural changes and gene expression changes in liver injury using HCV infection models. HCV uninfected, HCV infected and post-HCV infected excluded cells were constructed. In these cells, there were genes that changed reversibly or irreversibly in the process of HCV infection and HCV elimination. For further study, analysis of human liver chimera mice and patient specimens reveals genes that reversibly and irreversibly change in common in the three models, and thus liver damage after DAA treatment.
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Academic Significance and Societal Importance of the Research Achievements |
HCV感染は肝臓に持続感染して慢性肝炎、肝硬変、肝臓癌といった慢性肝障害を引き起こす。慢性肝障害は肝細胞のアポトーシス、リンパ球浸潤、脂肪肝などを伴う。さらに線維化が進行すると肝小葉が再構築され、肝臓の血液循環動態も変化する。従って、HCV持続感染による肝障害はウイルス感染そのもの、および宿主の免疫反応だけによるものではなく、肝臓の組織再構築による変化も関与することが考えられる。従って、DAA治療によりウイルス排除が達成された後も、引き続き肝障害が持続し、肝発がんに至ることもあり得る。
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Surfeit 4 contributes to the replication of hepatitis C virus using double membrane vesicles.2020
Author(s)
Kong L, Aoyagi H, Yang Z, Ouyang T, Matsuda M, Fujimoto A, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, Suzuki T, Suzuki T, Muramatsu M, Wakita T, Aizaki H.
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Journal Title
Journal of Virology
Volume: 94
Issue: 2
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Interferon sensitivity-determining region of hepatitis C virus influences virus production and interferon signaling2017
Author(s)
Sugiyama R., Murayama A., Nitta S., Yamada N., Tasaka-Fujita M., Masaki T., Aly H. H., Shiina M., Ryo A., Ishii K., Wakita T. and Kato T.
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Journal Title
Oncotarget
Volume: 9
Issue: 5
Pages: 5627-5640
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Characterization of miR-122-independent propagation of HCV2017
Author(s)
C. Ono, T. Fukuhara, D. Motooka, S. Nakamura, D. Okuzaki, S. Yamamoto, T. Tamura, H. Mori, A. Sato, K. Uemura, Y. Fauzyah, T. Kurihara, T. Suda, A. Nishio, Su Su Hmwe, T. Okamoto, T. Tatsumi, T. Takehara, K. Chayama, T. Wakita, K. Koike, Y. Matsuura
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Journal Title
PLoS Pathogens
Volume: -
Issue: 5
Pages: e1006374-e1006374
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Abnormal hepatocellular organelles are still present in patients with sustained virological response (SVR)2019
Author(s)
Haruyo Aoyagi, Hiroko Iijima, Minami Kikuchi, Maiko Koyama, Mami Matsuda, Koichi Watashi, Ryo suke Suzuki, Takahiro Masaki, Noritomo Shimada, Keizo Kato, Akihito Tsubota, Kenjiro Wake, Takaji Wakita, Hideki Aizaki
Organizer
26th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] Hepatitis C virus infection triggers the transactivation of aryl hydrocarbon receptor to rearrange hepatic lipid biosynthesis2018
Author(s)
Hirofumi Ohashi, Syo Nakajima, Sulyi Kim, Ryosuke Suzuki, Hideki Aizaki, Masayoshi Fukasawa, Shinji Kamisuki, Fumio Sugawara, Naoko Ohtani, Masamichi Muramatsu, Takaji Wakita, Koichi Watashi
Organizer
第66回日本ウイルス学会学術集会
Related Report
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[Presentation] Abnormal hepatocellular organelles remain to be observed in sustained virological response (SVR) patients2018
Author(s)
Haruyo Aoyagi, Hiroko Iijima, Xin Zheng, Yu Ting Kao, Gewaid E. Hossam, Mami Matsuda, Koichi Watashi, Ryosuke Suzuki, Takahiro Masaki, Noritomo Shimada, Keizo Kato, Akihito Tsubota, Ayako Mimata, Yuriko Sakamaki, Shizuko Ichinose, Kenjiro Wake, Takaji Wakita, Hideki Aizaki.
Organizer
第66回日本ウイルス学会学術集会
Related Report
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[Presentation] Aryl hydrocarbon receptor-cytochrome p450 1a1 pathway regulates hepatic lipid biosynthesis to maximize hepatitis C virus production2018
Author(s)
Hirofumi Ohashi, Syo Nakajima, Sulyi Kim, Ryosuke Suzuki, Hideki Aizaki, Masayoshi Fukasawa, Shinji Kamisuki, Kouji Kuramochi, Fumio Sugawara, Naoko Ohtani, Masamichi Muramatsu, Takaji Wakita, Koichi Watashi
Organizer
25th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] Flavivirus subviral particles-based DNA vaccine induces neutralizing antibodies against HCV2018
Author(s)
Keigo Yato, Mami Matsuda, Noriyuki Watanabe, Shogo Nakajima, Akira Fujimoto, Koichi Watashi, Hideki Aizaki, Takanobu Kato, Koji Tamura, Masamichi Muramatsu, Takaji Wakita, Ryosuke Suzuki
Organizer
25th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] Establishment of infectious genotype 4a HCVcc2018
Author(s)
Noriyuki Watanabe, Takaya Suzuki, Tomoko Date, Su Su Hmwe, Hussein H Aly, Hideki Aizaki, Masaya Sugiyama, Masashi Mizokami, Mohamed El Kassas, Ashraf Tabl, William IV Delaney, Guofeng Cheng, Masamichi Muramatsu, Takaji Wakita
Organizer
25th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] C型慢性肝炎のウイルス学的著効(SVR)後の肝実質細胞のオルガネラ異常の解析2017
Author(s)
青柳東代, 飯島尋子, Francesc Puig-Basagoiti, Zheng Xin, Yu Ting Kao, Gewaid E. Hossam, 在津拓馬, 松田麻未, 渡士幸一, 鈴木亮介, 政木隆博, 島田紀明, 加藤慶三, 坪田昭人, 三又絢子, 酒巻有里子, 市野瀬志津子, 和氣健二郎, 脇田隆字, 相崎英樹
Organizer
第27回抗ウイルス療法学会学術集会
Related Report
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[Presentation] Abnormal organelles were continuously observed in sustained virological response (SVR) patients2017
Author(s)
Aoyagi H, Iijima H, Puig-Basagoiti F, Zheng X, Kao YT, Gewaid HE, Zaitsu T, Matsuda M, Watashi K, Suzuki R, Masaki T, Shimada N, Kato K, Tsubota A, Mimata A, Sakamaki Y, Ichinose S, Wake K, Wakita T, Aizaki H
Organizer
he Asian Pacific Associaton for the Study of the Liver - Single Topic Conference 2017
Related Report
Int'l Joint Research
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[Presentation] Hepatic aryl hydrocarbon receptor-mediated lipid droplets production regulates the assembly efficacy of hepatitis C virus.2017
Author(s)
Hirofumi Ohashi, Syo Nakajima, Sulyi Kim, Ryosuke Suzuki, Hideki Aizaki, Masayoshi Fukasawa, Shinji Kamisuki, Fumio Sugawara, Naoko Ohtani, Takaji Wakita, Koichi Watashi
Organizer
24th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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