Development of human iPS cell-derived model for hepatocarcinogenesis
Project/Area Number |
17K19647
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
General internal medicine and related fields
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Asahina Yasuhiro 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (00422692)
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Co-Investigator(Kenkyū-buntansha) |
柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (30372444)
中川 美奈 東京医科歯科大学, 統合教育機構, 准教授 (30401342)
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Project Period (FY) |
2017-06-30 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | ヒトiPS細胞 / 肝細胞癌 / HBV / 発癌モデル / 肝星細胞 / HBV integration / iPS細胞 / HCV / HBV |
Outline of Final Research Achievements |
The genetic alterations responsible for HCC development and progression are unclear. Moreover, elucidation of mechanism for hepatocarcinogenesis involving host-viral genomic factors is hampered by lack of an appropriate in vitro human disease model. In this study, details of viral integration into the host genome associated with hepatocellular carcinoma were clarified, and the basis for the development of human iPS cell-derived in vitro model was constructed for analysing the mechanism responsible for these host-virus chimeric genome.
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Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、抗ウイルス療法によっても抑制できなかった肝発癌に対して、新たな対策を講じるための標的となる遺伝子要因が明らかとなった。また、ヒトiPS細胞を用いたin vitro解析モデル開発の技術的基盤を構築したことで、これまで未知であった癌化や病態形成のメカニズムが明らかとなる糸口が切り開かれた。さらに、本研究成果は、肝臓領域のみならず他のあらゆる臨床医学分野に応用可能であり、それぞれの分野における病態解明が加速することが期待される。
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Report
(4 results)
Research Products
(87 results)
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[Journal Article] JNJ-4178 (adafosbuvir, odalasvir, and simeprevir) in Japanese patients with chronic hepatitis C virus genotype 1 or 2 infection with or without compensated cirrhosis: The Phase IIa OMEGA-3 study.2020
Author(s)
Takehara T, Chayama K, Kurosaki M, Yatsuhashi H, Tanaka Y, Hiramatsu N, Sakamoto N, Asahina Y, Nozaki A, Nakano T, Hagiwara Y, Shimizu H, Yoshida H, Huang Y, Biermer M, Vijgen L, Hayashi N.
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Journal Title
J Gastroenterol
Volume: -
Issue: 6
Pages: 640-652
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Vasoactive Intestinal Peptide Derived From Liver Mesenchymal Cells Mediates Tight Junction Assembly in Mouse Intrahepatic Bile Ducts2020
Author(s)
Sato A, Kakinuma S, Miyoshi M, Kamiya A, Tsunoda T, Kaneko S, Tsuchiya J, Shimizu T, Takeichi E, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Koshikawa N, Seiki S, Nakauchi H, Asahina Y, Watanabe M.
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Journal Title
Hepatology Communications
Volume: 4
Issue: 2
Pages: 235-254
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma‐like area and metachronous hepatocellular carcinoma2019
Author(s)
Kawai-Kitahata F, Asahina Y, Kaneko S, Tsuchiya J, Sato A, Miyoshi M, Tsunoda T, Inoue-Shinomiya E, Murakawa M, Nitta S, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Tanabe M, Sugawara E, Takemoto A, Ojima H, Sakamoto M, Muraoka M, Takano S, Maekawa S, Enomoto N and Watanabe M.
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Journal Title
Hepatology Research
Volume: 49
Issue: 12
Pages: 1466-1474
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients2019
Author(s)
Nitta S, Asahina Y, Kato T, Tsuchiya J, Inoue-Shinomiya E, Sato A, Tsunoda T, Miyoshi M, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Hikita H, Takehara T, Watanabe M.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 5722-5722
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Loss of Fibrocystin Promotes Interleukin-8-Dependent Proliferation and CTGF Production of Biliary Epithelium.2019
Author(s)
Tsunoda T, Kakinuma S, Miyoshi M, Kamiya A, Kaneko S, Sato A, Tsuchiya J, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Sogo T, Komatsu H, Mukouchi R, Inui A, Fujisawa T, Nakauchi H, Asahina Y, Watanabe M.
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Journal Title
Journal of Heptatology
Volume: 印刷中
Issue: 1
Pages: 143-152
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] .Association of serum IFN-λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct-acting antiviral agents.2019
Author(s)
Emi Inoue-Shinomiya, Miyako Murakawa, Yasuhiro Asahina, Mina Nakagawa, Jun Tsuchiya, Ayako Sato, Tomoyuki Tsunoda, Masato Miyoshi, Sayuri Nitta, Fukiko Kawai-Kitahata, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Kazumoto Murata, Masashi Mizokami, Mamoru Watanabe.
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Journal Title
Hepatology Research
Volume: 印刷中
Issue: 5
Pages: 500-511
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] LIM homeobox 2 promotes interaction between human iPS-derived hepatic progenitors and iPS-derived hepatic stellate-like cells.2019
Author(s)
Miyoshi M, Kakinuma S, Kamiya A, Tsunoda T, Tsuchiya J, Sato A, Kaneko S, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Asahina Y, Watanabe M.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 2072-2072
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Diabetic Retinopathy as a Risk Factor Associated with the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.2019
Author(s)
Azuma S, Asahina Y, Kakinuma S, Azuma K, Miyoshi M, Inoue E, Tsunoda T, Sato A, Kaneko S, Nagata H, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Tomita M, Nakagawa M, Watanabe M.
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Journal Title
Digestive Diseases
Volume: 37
Issue: 3
Pages: 247-254
DOI
Related Report
Peer Reviewed
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[Journal Article] Ledipasvir-sofosbuvir for treating Japanese patients with chronic hepatitis C virus genotype 2 infection.2018
Author(s)
Asahina Y, Itoh Y, Ueno Y, Matsuzaki Y, Takikawa Y, Yatsuhashi H, Genda T, Ikeda F, Matsuda T, Dvory-Sobol H, Jiang D, Massetto B, Osinusi AO, Brainard DM, McHutchison JG, Kawada N, Enomoto N.
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Journal Title
Liver Int
Volume: 印刷中
Issue: 9
Pages: 1552-1561
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after the initial conventional TACE.2018
Author(s)
Yasui Y, Tsuchiya K, Kurosaki M, Takeguchi T, Takeguchi Y, Okada M, Wang W, Kubota Y, Goto T, Komiyama Y, Higuchi M, Takaura K, Hayashi T, Takada H, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Enomoto N, Himeno Y, Izumi N.
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Journal Title
Hepatol Res
Volume: 48
Issue: 6
Pages: 442-450
DOI
Related Report
Peer Reviewed
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[Journal Article] Association Between Alanine Aminotransferase Elevation And UGT1A1*6 Polymorphisms In Daclatasvir And Asunaprevir Combination Therapy For Chronic Hepatitis C.2017
Author(s)
Maekawa S, Sato M, Kuratomi N, Inoue T, Suzuki Y, Tatsumi A, Miura M, Matsuda S, Muraoka M, Nakakuki N, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Sato T, Sakamoto M, Murakawa M, Nakagawa M, Asahina Y, Enomoto N.
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Journal Title
J Gastroenterol
Volume: 印刷中
Issue: 6
Pages: 780-786
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C.2017
Author(s)
Nagata H, Nakagawa M, Asahina Y, Sato A, Asano Y, Tsunoda T, Miyoshi M, Kaneko S, Otani S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Nouchi T, Sakai H, Tomita M, Watanabe M
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Journal Title
J Hepatol
Volume: 67
Issue: 5
Pages: 933-939
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hepatic IFNL4 expression is associated with non-response to interferonbased therapy through the regulation of basal interferon-stimulated gene expression in chronic hepatitis C patients.2017
Author(s)
Murakawa M, Asahina Y, Kawai-Kitahata F, Nakagawa M, Nitta S, Otani S, Nagata H, Kaneko S, Asano Y, Tsunoda T, Miyoshi M, Itsui Y, Azuma S, Kakinuma S, Tanaka Y, Iijima S, Tsuchiya K, Izumi N, Tohda S, Watanabe M.
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Journal Title
J Med Virol
Volume: in press
Issue: 7
Pages: 1241-1247
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.2017
Author(s)
Murakawa M, Asahina Y, Nagata H, Nakagawa M, Kakinuma S, Nitta S, Kawai-Kitahata F, Otani S, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Sato A, Itsui Y, Azuma S, Nouchi T, Furumoto Y, Asano T, Chuganji Y, Tohda S, Watanabe M.
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 11
Pages: 1212-1218
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Hepatitis B Surface Antigen Reduction by Switching from Long-term Nucleoside/nucleotide Analog Administration to Pegylated Interferon.2017
Author(s)
Tamaki N, Kurosaki M, Kusakabe A, Orito E, Joko K, Kojima Y, Kimura H, Uchida Y, Hasebe C, Asahina Y, Izumi N.
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Journal Title
J Viral Hepat
Volume: 印刷中
Issue: 8
Pages: 672-678
DOI
Related Report
Peer Reviewed
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[Journal Article] Bone Morphogenetic Protein-4 Modulates Proliferation and Terminal Differentiation of Fetal Hepatic Stem/Progenitor Cells.2016
Author(s)
Goto F, Kakinuma S, Miyoshi M, Tsunoda T, Kaneko S, Sato A, Asano Y, Otani S, Azuma S, Nagata H, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Nakagawa M, Asahina Y, Watanabe M.
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 9
Pages: 941-952
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] The characteristic and the anti-HCV reagents susceptibility analysis of NS5A Resistance-Associated Substitutions (RAS) detected after DAA treatment failure patients.2018
Author(s)
Nitta S, Kato T, Tuchiya J, Inoue-Shinomiya E, Sato A, Tsunoda T, Miyoshi M, Kawai-Kitahata F, Murakawa M, Istui Y, Azuma S, Nakagawa M, Kakinuma S, Asahina Y.
Organizer
The 69th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2018)
Related Report
Int'l Joint Research
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[Presentation] The in vitro analysis of NS5A resistance-associated substitutions (RAS) observed in DAA treatment failure patients.2018
Author(s)
Sayuri Nitta, Takanobu Kato, Jun Tuchiya, Emi Inoue-Shinomiya, Ayako Sato, Tomoyuki Tsunoda, Masato Miyoshi, Fukiko Kawai-Kitahata, Miyako Murakawa, Yasuhiro Istui, Seishin Azuma, Mina Nakagawa, Sei Kakinuma, Yasuhiro Asahina.
Organizer
25th International Symposium on Hepatitis C Virus and Related Viruses
Related Report
Int'l Joint Research
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[Presentation] HBV Reactivation and changes in interferon-stimulated gene expression during treatment of direct-acting antivirals for HCV: analyses in a novel in vitro model for HBV-HCV coinfection using human induced pluripotent stem cell-derived hepatic cells.2018
Author(s)
Asahina Y, Kaneko S, Kakinuma S, Kamiya A, Miyoshi M, Tsunoda T, Inoue-Shinomiya E, Nitta S, Sato A, Asano Y, Nagata H, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Watanabe M.
Organizer
The 53red annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2018)
Related Report
Int'l Joint Research
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[Presentation] Difference of gene mutational profile among viral- and non-viral HCC with or without prior HBV infection: Results of comprehensive deep sequencing analyses of cancer genes and HBV/AAV integration.2018
Author(s)
Kawai-Kitahata F, Asahina Y, Kakinuma S, Murakawa M, Nitta S, Nagata H, Kaneko S, Inoue E, Miyoshi M, Tsunoda T, Sato A, Nakagawa M, Itsui Y, Azuma S, Tanaka S, Tanabe M, Maekawa S, Enomoto N, Watanabe M.
Organizer
The 53red annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2018)
Related Report
Int'l Joint Research
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[Presentation] 日本人のジェノタイプ2型C型慢性肝炎患者に対するLDV/SOF療法.2018
Author(s)
朝比奈靖浩, 伊藤義人, 上野義之, 松崎靖司, 滝川康裕, 八橋弘, 玄田拓哉, 池田房雄, 松田卓磨, Huang K, Massetto Benedetta, Osinusi Anu, Brainard Diana, McHutchison John, 河田則文, 榎本信幸.
Organizer
第54回日本肝臓学会総会
Related Report
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[Presentation] ヒトiPS細胞由来星細胞様細胞における転写因子LHX2の機能解析.2018
Author(s)
好正人, 柿沼晴, 金子俊, 紙谷聡英, 佐藤綾子, 角田知之, 四宮恵美, 北畑富貴子, 新田沙由梨, 村川美也子, 井津井康浩, 中川美奈, 東正新, 朝比奈靖浩, 渡辺守.
Organizer
第54回日本肝臓学会総会
Related Report
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[Presentation] HCV NS5Aキメラ株感染培養系を用いたNS5A阻害剤に対する耐性変異と薬剤感受性評価システムの構築.2018
Author(s)
新田沙由梨, 朝比奈靖浩, 佐藤綾子, 三好正人, 角田知之, 永田紘子, 金子俊, 北畑富貴子, 村川美也子, 中川美奈, 東正新, 柿沼晴, 加藤孝宣, 渡辺守.
Organizer
第54回日本肝臓学会総会
Related Report
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[Presentation] Twelve Weeks of Ledipasvir/Sofosbuvir All-oral Regimen for Patients with Chronic Hepatitis C Genotype 2 Infection: Integrated Analysis of Three Clinical Studies.2018
Author(s)
Asahina Y, Liu CJ, Gane E, Itoh Y, Kawada N, Ueno Y, Wang CY, Llewellyn J, Osinusi A, Svarovskaia J, Mo H, Crans G, Chuang WL, Chen PJ, Enomoto N.
Organizer
27th conference of the Asian Pacific Association for the Study of the Liver (APASL 2018)
Related Report
Int'l Joint Research
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[Presentation] Novel culture model for coinfection of hepatitis B and hepatitis C viruses using human induced pluripotent stem cell-derived hepatic cells for analyses of changes in host-innate immune responses.2017
Author(s)
Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Inoue-Shinomiya E, Nitta S, Sato A, Asano Y, Nagata H, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Watanabe M.
Organizer
The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2017)
Related Report
Int'l Joint Research
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[Presentation] Evaluation of an early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C patients treated with DAAs - Retrospective review of a prospective database -.2017
Author(s)
Nakagawa M, Asahina Y, Nagata H, Sato A, Miyoshi M, Tsunoda T, Asano Y, Kaneko S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Watanabe M.
Organizer
The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2017),
Related Report
Int'l Joint Research
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[Presentation] The analysis of NS5A Resistance-Associated Substitutions (RAS): In vitro study of NS5A recombinant hepatitis C in infectious cell culture system for various RAS detected after treatment failure in chronic hepatitis C patients.2017
Author(s)
Nitta S, Murakawa M, Kato T, Sato A, Tsunoda T, Miyoshi M, Asano Y, Kaneko S, Nagata H, Kawai-Kitahata F, Itsui Y, Nakagawa M, Azuma S, Kakinuma S, Asahina Y.
Organizer
The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2017)
Related Report
Int'l Joint Research
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[Presentation] On-treatment higher levels of alpha-fetoprotein and M2BPGi are associated with development of hepatocellular carcinoma during nucleos(t)ide analog therapy in patients with HBV chronic infection.2017
Author(s)
Murakawa M, Asahina Y, Nakagawa M, Sato A, Miyoshi M, Tsunoda T, Asano Y, Nagata H, Kaneko S, Kawai-Kitahata F, Nitta S, Itsui Y, Azuma S, Kakinuma S, Watanabe M.
Organizer
The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2017)
Related Report
Int'l Joint Research
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[Presentation] Ledipasvir/Sofosbuvir in the Treatment of Japanese Patients with Chronic HCV Genotype 2 Infection.2017
Author(s)
Asahina Y, Itoh Y, Ueno Y, Matsuzaki Y, Takikawa Y, Yatsuhashi H, Genda T, Ikeda F, Matsuda T, Jiang D, Huang KC, Massetto B, Osinusi A, Brainard DM, McHutchison JG, Kawada N, Enomoto N.
Organizer
The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2017)
Related Report
Int'l Joint Research
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[Presentation] Genetic differences in hepatocellular carcinoma among chronic persistent hepatitis B virus (HBV) infection with or without viral suppression and prior HBV infection.2017
Author(s)
Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Nitta S, Watanabe T, Otani S, Goto F, Nagata H, Kaneko S, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Maekawa S, Enomoto N, Watanabe M.
Organizer
The 52th annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2017)
Related Report
Int'l Joint Research
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[Presentation] 慢性肝疾患の線維化発がん阻止への展望 ヒトiPS細胞由来肝臓系譜細胞による病態モデルの作成と先天性肝線維症の病態解析.2017
Author(s)
角田知之, 柿沼 晴, 三好正人, 佐藤綾子, 四宮恵美, 金子 俊, 浅野 侑, 村川美也子, 新田沙由梨, 井津井康浩, 東 正新, 中川美奈, 朝比奈靖浩, 渡辺 守.
Organizer
第54回日本消化器免疫学会総会
Related Report
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