Comprehensive analyses of gene mutational profile and viral integration in hepatocellular carcinoma and development of novel human iPS cells-derived disease model

• Project/Area Number: 16H05285
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• 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)
• 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)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 肝癌 / HBV / HCV / ヒトiPS細胞 / Viral integration / HBV integration / iPS細胞 / 肝細胞癌 / Ｂ型肝炎ウイルス / C型肝炎ウイルス / ゲノム / 次世代シークエンス

Outline of Final Research Achievements

In this study, host and viral genetic factors related to hepatocellular carcinoma were analyzed. As a result, no difference in cancer gene mutational profile was found between presence and absence of HCV infection, suggesting the presence of common oncogenic mechanism between them. On the other hand, in the case of HBV persistent infection, TERT promoter mutation, but not HBV integration, might be reduced in the condition with HBV suppression by nucleoside/nucleotide analogues. Furthermore, culture methods and virus infection systems in human iPS cells were developed, and an intellectual and technical basis was obtained to develop a human iPS cells-derived analytical model using genetic editing technology.

Academic Significance and Societal Importance of the Research Achievements

本研究ではNGS技術を駆使してHCV排除後やHBV持続感染、及び非ウイルス性肝癌に関わる癌ゲノムプロファイルを明らかとした。また、ヒトiPS細胞培養技術、ウイルス培養系、及び遺伝子改変技術を応用した疾患病態解析モデルを開発し、より生理的条件に近い状態での発癌・病態形成機構の解明を可能とする知的・技術的基盤を確立した。本研究の遂行により、未だ根本的治療法の存在しない、ウイルス性・非ウイルス性肝疾患及び肝癌における、これまでとは視点を異にする新規治療法開発への展開が期待される。更に、これらの研究成果は他分野に広く応用可能である。

Research Products

• [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.
  • Journal Title: Journal of Heptatology Volume: 印刷中 Issue: 1 Pages: 143-152
  • DOI: 10.1016/j.jhep.2019.02.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice (2019)
  • Author(s): Doi Akira、Hikita Hayato、Kai Yugo、Tahata Yuki、Saito Yoshinobu、Nakabori Tasuku、Yamada Ryoko、Kodama Takahiro、Sakamori Ryotaro、Murayama Asako、Nitta Sayuri、Asahina Yasuhiro、Suemizu Hiroshi、Tatsumi Tomohide、Kato Takanobu、Takehara Tetsuo
  • Journal Title: Journal of Gastroenterology Volume: 54 Issue: 5 Pages: 449-458
  • DOI: 10.1007/s00535-018-01541-x
  • Peer Reviewed
• [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.
  • Journal Title: Hepatology Research Volume: 印刷中 Issue: 5 Pages: 500-511
  • DOI: 10.1111/hepr.13307
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 2072-2072
  • DOI: 10.1038/s41598-018-37430-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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.
  • Journal Title: Digestive Diseases Volume: 37 Issue: 3 Pages: 247-254
  • DOI: 10.1159/000493580
  • Peer Reviewed
• [Journal Article] Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients With Chronic HBV Infection (2018)
  • Author(s): Seto Wai-Kay、Asahina Yasuhiro、Brown Todd T.、Peng Cheng-Yuan、Stanciu Carol、Abdurakhmanov Dzhamal、Tabak Fehmi、Nguyen Tuan T.、Chuang Wan-Long、Inokuma Tetsuro、Ikeda Fusao、Santantonio Teresa Antonia、Habersetzer Fran?ois、Ramji Alnoor、Lau Audrey H.、Suri Vithika、Flaherty John F.、Wang Hongyuan、et al.
  • Journal Title: Clinical Gastroenterology and Hepatology Volume: －
  • DOI: 10.1016/j.cgh.2018.06.023
  • Peer Reviewed / Int'l Joint Research
• [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.
  • Journal Title: Liver Int Volume: 印刷中 Issue: 9 Pages: 1552-1561
  • DOI: 10.1111/liv.13685
  • Peer Reviewed / Int'l Joint Research
• [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.
  • Journal Title: Hepatol Res Volume: 48 Issue: 6 Pages: 442-450
  • DOI: 10.1111/hepr.13048
  • Peer Reviewed
• [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.
  • Journal Title: J Gastroenterol Volume: 印刷中 Issue: 6 Pages: 780-786
  • DOI: 10.1007/s00535-017-1405-3
  • Peer Reviewed / Open Access
• [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
  • Journal Title: J Hepatol Volume: 67 Issue: 5 Pages: 933-939
  • DOI: 10.1016/j.jhep.2017.05.028
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: J Med Virol Volume: in press Issue: 7 Pages: 1241-1247
  • DOI: 10.1002/jmv.24763
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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.
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 11 Pages: 1212-1218
  • DOI: 10.1111/hepr.12867
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genome-wide association study identifies TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus. (2017)
  • Author(s): Matsuura K, Asahina Y, Tanaka Y, et al.
  • Journal Title: Gastroenterology Volume: 152 Pages: 1383-1394
  • Peer Reviewed
• [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.
  • Journal Title: J Viral Hepat Volume: 印刷中 Issue: 8 Pages: 672-678
  • DOI: 10.1111/jvh.12691
  • Peer Reviewed
• [Journal Article] Genome-wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection. (2017)
  • Author(s): Matsuura K, Honda M, et al.
  • Journal Title: Gastroenterology. Volume: - Issue: 6 Pages: 1383-1394
  • DOI: 10.1053/j.gastro.2017.01.041
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Complex pattern of resistance-associated substitutions of hepatitis C virus after daclatasvir/asunaprevir treatment failure. (2017)
  • Author(s): Itakura J, Kurosaki M, Hasebe C, Osaki Y, Joko K, Yagisawa H, Sakita S, Okushin H, Satou T, Hisai H, Abe T, Tsuji K, Tamada T, Kobashi H, Mitsuda A, Ide Y, Ogawa C, Tsuruta S, Takaguchi K, Murakawa M, Asahina Y, Enomoto N, Izumi N.
  • Journal Title: PLoS One Volume: － Issue: 10 Pages: e0165339-e0165339
  • DOI: 10.1371/journal.pone.0165339
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: Hepatol Res Volume: 印刷中 Issue: 9 Pages: 941-952
  • DOI: 10.1111/hepr.12823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents. (2016)
  • Author(s): Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 34652-34652
  • DOI: 10.1038/srep34652
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma. (2016)
  • Author(s): Takada H, Tsuchiya K, Yasui Y, Nakakuki N, Tamaki N, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Asahina Y, Enomoto N, Izumi N.
  • Journal Title: Cancer Med Volume: 5 Issue: 11 Pages: 3111-3120
  • DOI: 10.1002/cam4.932
  • Peer Reviewed
• [Journal Article] Serial measurement of Wisteria floribunda agglutinin positive Mac-2-binding protein is useful for predicting liver fibrosis and the development of hepatocellular carcinoma in chronic hepatitis C patients treated with IFN-based and IFN-free therapy. (2016)
  • Author(s): Nagata H, Nakagawa M, Nishimura-Sakurai Y, Asano Y, Tsunoda T, Miyoshi M, Kaneko S, Goto F, Otani S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Seishin Azuma S, Kakinuma S, Tojo N, Tohda T, Asahina Y, Watanabe M, the Ochanomizu Liver Conference Study Group.
  • Journal Title: Hepatol Int Volume: 10 Issue: 6 Pages: 956-964
  • DOI: 10.1007/s12072-016-9754-1
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human induced pluripotent stem cell-derived hepatic cell line as a new model for host interaction with hepatitis B virus. (2016)
  • Author(s): Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Asano Y, Nagata H, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Iwamoto M, Watashi K, Wakita T, Sugiyama M, Mizokami M, Shimotohno K, Watanabe M.
  • Journal Title: Sci Rep Volume: ６ Issue: 1 Pages: 29358-29358
  • DOI: 10.1038/srep29358
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of IFN resistance in newly established genotype 1b HCV cell culture system. (2016)
  • Author(s): Taniguchi M, Tasaka-Fujita M, Nakagawa M, Watanabe T, Kawai-Kitahata F, Otani S, Goto F, Nagata H, Kaneko S, Nitta S, Murakawa M, Nishimura-Sakurai Y, Azuma S, Itsui Y, Mori K, Yagi S, Kakinuma S, Asahina Y, Watanabe M.
  • Journal Title: J Clin Transl Hepatol Volume: 4 Issue: 1 Pages: 5-11
  • DOI: 10.14218/jcth.2015.00047
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Matrix Metalloproteinase-14 Mediates Formation of Bile Ducts and Hepatic Maturation of Fetal Hepatic Progenitor Cells. (2016)
  • Author(s): Otani S, Kakinuma S, Kamiya A, Goto F, Kaneko S, Miyoshi M, Tsunoda T, Asano Y, Kawai-Kitahata F, Nitta S, Nakata T, Okamoto R, Itsui Y, Nakagawa M, Azuma S, Asahina Y, Yamaguchi T, Koshikawa N, Seiki M, Nakauchi H, Watanabe M.
  • Journal Title: Biochem Biophys Res Commun Volume: 469 Issue: 4 Pages: 1062-1068
  • DOI: 10.1016/j.bbrc.2015.12.105
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features. (2016)
  • Author(s): Kawai-Kitahata F, Asahina Y, Tanaka S, Kakinuma S, Murakawa M, Sayuri Nitta S, Watanabe T, Otani S, Taniguchi M, Goto F, Nagata H, Kaneko S, Tasaka-Fujita M, Nishimura-Sakurai Y, Azuma S, Itsui Y, Nakagawa M, Tanabe M, Takano S, Fukasawa M, Sakamoto M, Maekawa S, Enomoto N, Watanabe M.
  • Journal Title: Journal of Gastroenterology Volume: 51 Issue: 5 Pages: 473-486
  • DOI: 10.1007/s00535-015-1126-4
  • Peer Reviewed
• [Journal Article] Efficacy of additional radiofrequency ablation after transcatheter arterial chemoembolization for intermediate hepatocellular carcinoma. (2016)
  • Author(s): Azuma S, Asahina Y, Nishimura-Sakurai Y, Kakinuma S, Kaneko S, Nagata H, Goto F, Ootani S, Kawai-Kitahata F, Taniguchi M, Murakawa M, Watanabe T, Tasaka-Fujita M, Itsui Y, Nakagawa M, Watanabe M.
  • Journal Title: Heptol Res Volume: 46 Issue: 4 Pages: 312-9
  • DOI: 10.1111/hepr.12566
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2. (2016)
  • Author(s): Asahina Y, Izumi N, Hiromitsu K, Kurosaki M, Koike K, Suzuki F, Takikawa H, Tanaka A, Tanaka E, Tanaka Y, Tsubouchi H, Hayashi N, Hiramatsu N, Yotsuyanagi H
  • Journal Title: Hepatol Res Volume: 46 Issue: 2 Pages: 129-165
  • DOI: 10.1111/hepr.12645
  • Peer Reviewed
• [Journal Article] Need for appropriate programs for prevention of hepatitis B infection: lessons from the latest nationwide survey in Japan. (2016)
  • Author(s): Asahina Y, Watanabe M
  • Journal Title: J Gastroenterol Hepatol Volume: 31 Issue: 1 Pages: 12-13
  • DOI: 10.1111/jgh.13157
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Increased risk of HCC following DAA: fact or fiction? / Follow up strategy after SVR in chronic hepatitis C. (2018)
  • Author(s): Asahina Y.
  • Organizer: Asian Pacific Digestive Week 2018
  • Int'l Joint Research / Invited
• [Presentation] Gene mutational profile and viral integration in hepatocellular carcinoma with or without HBV/HCV suppression. (2018)
  • Author(s): Asahina Y, Kitahata-Kawai F, Murakawa M, Nitta S, Nakagawa M, Kakinuma S, Watanabe M.
  • Organizer: The 69th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2018)
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [Presentation] Post-treatment M2BPGi level is useful for predicting HCC occurrence and recurrence after viral eradication in chronic hepatitis C patients. (2018)
  • Author(s): Nakagawa M, Asahina Y, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Tomita M, Watanabe M and the Ochanomizu Liver Conference Study Group.
  • Organizer: The 69th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2018)
  • Int'l Joint Research
• [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
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [Presentation] 肝発癌の完全制御を目指したC型慢性肝疾患SVR後サーベイランスの検討． (2018)
  • Author(s): 中川美奈, 村川美也子, 朝比奈靖浩．
  • Organizer: 第42回日本肝臓学会東部会
• [Presentation] 肝間葉系細胞との細胞間相互作用を介した胆管形成の分子機序． (2018)
  • Author(s): 佐藤綾子, 柿沼晴, 朝比奈靖浩．
  • Organizer: 第42回日本肝臓学会東部会
• [Presentation] F0の背景肝から発症した肝細胞癌における癌関連遺伝子変異とviral integrationの検討． (2018)
  • Author(s): 北畑富貴子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第42回日本肝臓学会東部会
• [Presentation] iPS細胞先天性肝線維症病態モデルによる胆管細胞異常に起因する肝線維化における免疫応答の解析． (2018)
  • Author(s): 角田知之, 柿沼晴, 朝比奈靖浩．
  • Organizer: 第42回日本肝臓学会東部会
• [Presentation] 免疫抑制状態によるE型肝炎慢性化症例の解析． (2018)
  • Author(s): 井津井康浩, 北畑富貴子, 新田沙由梨, 村川美也子, 中川美奈, 東正新, 柿沼晴, 朝比奈靖浩, 渡辺守．
  • Organizer: 第42回日本肝臓学会東部会
• [Presentation] B型慢性肝疾患に対する核酸アナログ治療例・未治療例における発癌背景因子の解析． (2018)
  • Author(s): 村川美也子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第22回日本肝臓学会大会
• [Presentation] Direct acting antivirals(DAA)治療不成功で認められる新規NS5A resistant associated substitutions(RAS)の特性と各種抗HCV薬に対する感受性の全長ウイルスを用いた基礎的検討． (2018)
  • Author(s): 新田沙由梨, 朝比奈靖浩, 渡辺守．
  • Organizer: 第22回日本肝臓学会大会
• [Presentation] HCVウイルスおよび宿主変異がDAA治療後肝発癌に与える影響． (2018)
  • Author(s): 中川美奈, 朝比奈靖浩, 渡辺守．
  • Organizer: 第22回日本肝臓学会大会
• [Presentation] 癌関連遺伝子変異とウイルスのヒトゲノムへの挿入から検討する肝炎ウイルス制御下肝細胞癌の病態． (2018)
  • Author(s): 北畑富貴子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第54回日本肝臓学会総会
• [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
• [Presentation] HBs抗原陰性化を目指した治療戦略 B型慢性肝疾患の長期経過におけるウイルス動態およびHBs抗原陰性化予測因子の検討． (2018)
  • Author(s): 村川美也子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] DAA治療後の耐性ウイルス出現と肝発癌の完全制御を目指した治療戦略． (2018)
  • Author(s): 中川美奈, 朝比奈靖浩, 渡辺守．
  • Organizer: 第54回日本肝臓学会総会
• [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
• [Presentation] DAAs治療によるHCV排除後の肝発癌抑止効果の検討． (2018)
  • Author(s): 永田紘子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] 肝癌の臨床検体を用いた癌関連遺伝子プロファイルと病態の解析． (2018)
  • Author(s): 北畑富貴子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第104回日本消化器病学会総会
• [Presentation] C型肝炎治療:現状と展望 治療不成功により生じたNS5A変異ウイルスの特性と各種抗ウイルス薬に対する感受性の検討． (2018)
  • Author(s): 新田沙由梨, 朝比奈靖浩, 渡辺守．
  • Organizer: 第104回日本消化器病学会総会
• [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)
  • Int'l Joint Research
• [Presentation] Host genome mutations and HBV integration in HCC patients with HBV infection. (2018)
  • Author(s): Asahina Y.
  • Organizer: 36th US-Japan Hepatitis Panel Meeting New Approaches to HBV Therapy.
  • Int'l Joint Research / Invited
• [Presentation] Gap between real world data and the clinical trial with DAA for HCV. (2017)
  • Author(s): Asahina Y.
  • Organizer: Taiwan Association for the Study of the Liver 2017
  • Int'l Joint Research / Invited
• [Presentation] Occurrence and recurrence of hepatocellular carcinoma (HCC) in HCV patients treated with direct acting antiviral agents. (2017)
  • Author(s): Asahina Y.
  • Organizer: Korean Association for the Study of the Liver 2017
  • Int'l Joint Research / Invited
• [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)
  • Int'l Joint Research
• [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),
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [Presentation] HCC with or without viral suppression and new predictive biomarkers. (2017)
  • Author(s): Asahina Y.
  • Organizer: Taiwan Digestive Diseases Week 2017
  • Int'l Joint Research / Invited
• [Presentation] Diabetic retinopathy as a risk factor associated with development of hepatocellular carcinoma in non-alcoholic fatty liver disease. (2017)
  • Author(s): Azuma S, Asahina Y, Kakinuma S, Azuma K, Watanabe M.
  • Organizer: Asian Pacific Digestive Week 2017
  • Int'l Joint Research
• [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)
  • Int'l Joint Research
• [Presentation] Risk factors for HCC in patients with HCV after anti-viral treatment. (2017)
  • Author(s): Asahina Y.
  • Organizer: The 11th APASL Single Topic Conference
  • Int'l Joint Research / Invited
• [Presentation] SVR100%を目指すDAAs治療 C型慢性肝炎に対するインターフェロンフリー治療不成功および治療後発癌例の検討． (2017)
  • Author(s): 中川美奈, 朝比奈靖浩, 渡辺守．
  • Organizer: 第21回日本肝臓学会大会
• [Presentation] C型慢性肝炎に対するIFN-based、IFN-free治療後SVR後発癌および発癌予測因子についての検討． (2017)
  • Author(s): 永田紘子, 中川美奈, 朝比奈靖浩．
  • Organizer: 第21回日本肝臓会大会
• [Presentation] HBV再活性化対策のup-to-date HBV-HCV共感染時における抗HCV－DAA治療に伴うHBV再活性化機構の解析． (2017)
  • Author(s): 金子俊, 柿沼晴, 朝比奈靖浩．
  • Organizer: 第21回日本肝臓学会大会
• [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
• [Presentation] C型肝炎の最新治療と新たなる課題. (2017)
  • Author(s): 朝比奈靖浩.
  • Organizer: 第16回日本ウイルス学会
  • Invited
• [Presentation] 肝炎ウイルス制御下およびB型肝炎ウイルス既往感染におけるにおける肝細胞癌遺伝子変異の検討． (2017)
  • Author(s): 北畑富貴子，朝比奈靖浩，田中真二，村川美也子，新田沙由梨，柿沼晴，永田紘子，金子俊，浅野侑，角田知之，三好正人，井上恵美，佐藤綾子，井津井康浩，中川美奈，東正新，田邉稔，前川伸哉，榎本信幸，渡辺守．
  • Organizer: 第53回日本肝癌研究会
• [Presentation] C型肝炎の最新治療と新たなる課題. (2017)
  • Author(s): 朝比奈靖浩.
  • Organizer: 第30回日本消化器病学会関東支部教育講演
  • Invited
• [Presentation] 日本肝臓学会ガイドラインup to date HCV感染と肝発癌. (2017)
  • Author(s): 朝比奈靖浩.
  • Organizer: 第53回日本肝臓学会総会
  • Invited
• [Presentation] ウイルス制御を目指したB型肝炎の治療戦略 B型慢性肝炎TDFまたはTAF投与例における骨密度の変化． (2017)
  • Author(s): 朝比奈靖浩, 泉並木．
  • Organizer: 第53回日本肝臓学会総会
  • Invited
• [Presentation] B型肝炎研究の新展開 ヒトiPS細胞由来肝細胞系譜細胞を用いたB型肝炎ウイルス感染への宿主自然免疫応答の解析． (2017)
  • Author(s): 金子俊, 柿沼晴, 朝比奈靖浩．
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] C型肝炎SVR後の問題点 C型慢性肝炎に対するIFN-based、IFN-free治療後発癌および発癌予測因子についての検討． (2017)
  • Author(s): 永田紘子, 中川美奈, 朝比奈靖浩．
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] ウイルス性肝炎の病態解析と新規治療 B型肝炎ウイルス制御下における肝細胞癌遺伝子変異の検討． (2017)
  • Author(s): 北畑富貴子, 朝比奈靖浩, 渡辺守．
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] C型肝炎インターフェロンフリー治療の現況 C型慢性肝疾患に対するインターフェロンフリー治療の有効性の検討． (2017)
  • Author(s): 中川美奈, 朝比奈靖浩, 渡辺守．
  • Organizer: 第103回日本消化器病学会大会
• [Presentation] 非ウイルス性肝癌の現況と治療戦略 非B非C型肝細胞癌の臨床背景． (2016)
  • Author(s): 東 正新, 朝比奈 靖浩, 渡辺 守．
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-12-08
• [Presentation] B型肝炎 根治を目指して HBV関連肝疾患における核酸アナログ治療効果と肝発癌の関連 (2016)
  • Author(s): 村川 美也子, 朝比奈 靖浩, 渡辺 守．
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-12-08
• [Presentation] C型肝炎の残された問題点 C型慢性肝疾患に対するインターフェロンフリー治療の効果と安全性の検討 (2016)
  • Author(s): 中川 美奈, 村川 美也子, 朝比奈 靖浩
  • Organizer: 第41回日本肝臓学会東部会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-12-08
• [Presentation] Reduced changes in bone mineral density in CHB patients receiving tenofovir alfenamide (TAF) compared with tenofovir disoproxil fumarate. (2016)
  • Author(s): Seto WK, Asahina Y, Peng, Stanciu CYC, Abdurakhmanov D, Flaherty JF, Kim K, Gaggar A, Subramanian M, Tabak F, Tuan T. Nguyen TT, Chan HLT.
  • Organizer: The 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2016).
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] Genetically modified human induced pluripotent stem cell-derived hepatic progenitor-like cell lines as a model for interaction between hepatitis В virus and host cells. (2016)
  • Author(s): Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Sato A, Asano Y, Nagata H, Otani S, Kawai-Kitahata F, Murakawa M, Nakagawa M, Azuma S, Watanabe M.
  • Organizer: The 67th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2016).
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] 肝疾患バイオマーカーの新知見 C型慢性肝炎に対する抗ウイルス治療後の発癌予測因子の検討 (2016)
  • Author(s): 永田 紘子, 中川 美奈, 朝比奈 靖浩
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-03
• [Presentation] 肝炎ウイルス制御下時代の肝癌診療 宿主ゲノム変異の網羅的解析からみたウイルス制御下における発癌の検討 (2016)
  • Author(s): 北畑 富貴子, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-03
• [Presentation] C型慢性肝疾患に対する抗ウイルス治療の意義の検討 (2016)
  • Author(s): 中川 美奈, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第20回日本肝臓学会大会
  • Place of Presentation: 神戸コンベンションセンター（兵庫県神戸市）
  • Year and Date: 2016-11-03
• [Presentation] C型慢性肝疾患における抗ウイルス療法と発癌抑止効果：ポストC型肝炎ウイルス時代における今後の課題． (2016)
  • Author(s): 朝比奈靖浩
  • Organizer: 第52回日本肝癌研究会
  • Place of Presentation: 虎ノ門ヒルズフォーラム（東京都港区）
  • Year and Date: 2016-07-01
  • Invited
• [Presentation] 明日から役立つ肝臓病理 Viral Hepatitis ウイルス性肝炎の線維化診断におけるM2BPGiの意義とその機序における病理学的考察 (2016)
  • Author(s): 永田 紘子, 中川 美奈, 朝比奈 靖浩
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張、東京ベイ幕張ホール（千葉県美浜区）
  • Year and Date: 2016-05-19
• [Presentation] C型肝炎治療の新時代に向けて C型慢性肝疾患に対するインターフェロンフリー治療の効果と安全性の検討 (2016)
  • Author(s): 中川 美奈, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張、東京ベイ幕張ホール（千葉県美浜区）
  • Year and Date: 2016-05-19
• [Presentation] 抗ウイルス療法による発癌抑制効果 (2016)
  • Author(s): 朝比奈 靖浩
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ幕張、東京ベイ幕張ホール（千葉県美浜区）
  • Year and Date: 2016-05-19
• [Presentation] 新規技術を用いた肝疾患診療の未来 診断から治療へ C型慢性肝炎に対するIFN-based/free治療の比較とMac2 Binding Protein(M2BP)Giの有用性の検討 (2016)
  • Author(s): 中川 美奈, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
• [Presentation] 肝癌の病態解明を見据えた新戦略 肝細胞癌の病態に関連する宿主ゲノム変異とB型肝炎ウイルスX蛋白の機能解析 (2016)
  • Author(s): 北畑 富貴子, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
• [Presentation] C型肝炎治療の新時代と将来への展望 C型慢性肝炎治療後の発癌リスクを考慮した治療戦略 (2016)
  • Author(s): 村川 美也子, 朝比奈 靖浩, 渡辺 守
  • Organizer: 第102回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
• [Presentation] A model for interaction between HBV and host cells derived from human induced pluripotent stem cells. (2016)
  • Author(s): Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Nitta S, Tsunoda T, Miyoshi M, Asano Y, Nagata H, Goto F, Otani S, Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma AS, Watanabe M.
  • Organizer: The 51th annual meeting of the European association for the study of the liver (EASL The International Liver Congress 2016).
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2016-04-13
  • Int'l Joint Research
• [Presentation] Recent progress in anti-HCV therapy and challenges toward HCC eradication. (2016)
  • Author(s): Asahina Y
  • Organizer: Academic Forum of Liver Disease in Northeast China and the Annual Convention for the Study of Liver Diseases in Jilin Province in 2016
  • Place of Presentation: Changchun, China
  • Int'l Joint Research / Invited
• [Presentation] Hepatocarcinogenesis after hepatitis C viral eradication. (2016)
  • Author(s): Asahina Y
  • Organizer: The 10th APASL Single Topic Conference
  • Place of Presentation: Kaoshiung, Taiwan
  • Int'l Joint Research / Invited