Establishment of highly safe gene therapy without usage of double stranded DNA

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17H06269
• Research Institution: Hiroshima University
• Principal Investigator: 茶山 一彰 広島大学, 医系科学研究科(医), 教授 (00211376)
• Co-Investigator(Kenkyū-buntansha): 三木 大樹 広島大学, 医系科学研究科(医), 講師 (10584592) ; 茶山 弘美 広島大学, 医系科学研究科(医), 准教授 (70572329) ; 林 亮平 広島大学, 病院(医), 病院助教 (80772053)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: genome editing / lentivirus / dsDNA / cancer therapy

Outline of Annual Research Achievements

遺伝子治療のターゲットは遺伝性疾患、癌、ウイルス感染症など多岐にわたる。遺伝性疾患の多くを占める劣性遺伝の形式を取るものでは遺伝子の改変(正常化)により細胞としての機能を回復するものが多く存在する。遺伝子治療は望ましい治療ではあるが、これまで遺伝子の改変が容易に行える手法が無かったことから、その実施は困難であると見なされてきた。最近開発されたCRISPR/cas9システムを使用すれば遺伝子のknock inが可能であり、遺伝子治療の画期的な進展が期待される。しかし、2本鎖DNAの宿主遺伝子への挿入は不必要な遺伝子の挿入による不必要な遺伝子改変が起こってしまうリスクを伴う。本研究では2本鎖DNAを使用しないで遺伝子改変を行うシステムを構築することを目的として研究を開始した。まず、ゲノム編集を行うために実際にknock inが出来るシステムを構築する実験を行った。この目的でcas9、guide RNA、donor DNAを搭載するall in one typeのlentivirus vectorの作製を行った。しかし、insert sizeが大きいためか、算出されたlentivirusのRNA濃度を元に算出したウイルスタイターと、実際の感染効率との間に大きな差異が生じた。このため、cas9のみとguide RNAおよびdonor DNAを含む2つのlentivirus vectorを作製し、ウイルス粒子を作製、感染により目的としたゲノム編集が行えるかどうかを検討した。donor DNAには薬剤による選択が可能となるようにpuromycin耐性遺伝子を用いた。ウイルス感染後、細胞をpuromycin存在下に培養し、得られた細胞クローンの標的遺伝子剤をPCRにより増幅、目的としたゲノム編集が行えていることを確認した。今後deliveryの検討を行う。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Regression of Idiopathic Thrombocytopenic Purpura in a Patient With Eradication of Hepatitis C Virus by Direct-Acting Antivirals. (2020)
  • Author(s): Johira Y, Hatooka H, Mori N, Fukuhara T, Takaki S, Shimomura Y, Imamura M, Hayes CN, Tsuji K, Chayama K.
  • Journal Title: Hepatology. Volume: 71 Pages: 389-391
  • DOI: 10.1002/hep.30900.
  • Peer Reviewed / Open Access
• [Journal Article] Successful retreatment with 12 weeks of glecaprevir and pibrentasvir for a genotype 2a HCV-infected hemodialysis patient who failed to respond to 8 weeks of prior glecaprevir and pibrentasvir therapy. (2020)
  • Author(s): Ohya K, Imamura M, Osawa M, Teraoka Y, Morio K, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Hiramatsu A, Tsuge M, Aikata H, Hayes CN, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: 13 Pages: 267-270
  • DOI: 10.1007/s12328-019-01039-w.
  • Peer Reviewed / Open Access
• [Journal Article] Management of refractory ascites attenuates muscle mass reduction and improves survival in patients with decompensated cirrhosis. (2020)
  • Author(s): Namba M, Hiramatsu A, Aikata H, Kodama K, Uchikawa S, Ohya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Tsuge M, Imamura M, Chayama K.
  • Journal Title: J Gastroenterol. Volume: 55 Pages: 217-226
  • DOI: 10.1007/s00535-019-01623-4.
  • Peer Reviewed / Open Access
• [Journal Article] Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV-infected Japanese Subjects in Phase 3 CERTAIN-1 and CERTAIN-2 Trials. (2020)
  • Author(s): Suleiman AA, Lin CW, Liu W, Eckert D, Mensing S, Burroughs M, Kato K, Chayama K, Kumada H, Oberoi RK.
  • Journal Title: J Clin Pharmacol. Volume: 60 Pages: 331-339
  • DOI: 10.1002/jcph.1524.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan. (2020)
  • Author(s): Kawaguchi I, Chayama K, Gonzalez YS, Virabhak S, Mitchell D, Yuen C, Kumada H.
  • Journal Title: Adv Ther. Volume: 37 Pages: 457-476
  • DOI: 10.1007/s12325-019-01166-3.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Three Children Treated with Direct-acting Antivirals for Chronic Hepatitis C Virus Genotype 1b Infection. (2020)
  • Author(s): Ohya K, Kawaoka T, Imamura M, Morio K, Nakahara T, Murakami E, Yamauchi M, Hiramatsu A, Tsuge M, Aikata H, Chayama K.
  • Journal Title: Intern Med. Volume: 59 Pages: 941-944.
  • DOI: 10.2169/internalmedicine.3824-19.
  • Peer Reviewed / Open Access
• [Journal Article] Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases. (2020)
  • Author(s): Daijo K, Nakahara T, Inagaki Y, Nanba M, Nishida Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Ono A, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Imamura M, Aikata H, Ochi H, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: - Pages: -
  • DOI: 10.1111/jgh.14968.
• [Journal Article] Preoperative PET-CT is useful for predicting recurrent extrahepatic metastasis of hepatocellular carcinoma after resection. (2020)
  • Author(s): Morio K, Kawaoka T, Aikata H, Namba M, Uchikawa S, Kodama K, Ohya K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Nakamura Y, Akagi M, Awai K, Kobayashi T, Ohdan H, Chayama K.
  • Journal Title: Eur J Radiol. Volume: 124 Pages: 108828
  • DOI: 10.1016/j.ejrad.2020.108828.
  • Peer Reviewed / Open Access
• [Journal Article] A case of advanced HCC treated with lenvatinib after hepatic arterial infusion chemotherapy combined with radiation therapy treatment for portal vein tumor thrombosis in the main trunk. (2020)
  • Author(s): Kosaka Y, Kawaoka T, Aikata H, Suehiro Y, Yamaoka K, Ando Y, Namba M, Takeuchi Y, Fujii Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Baba Y, Awai K, Kimura T, Nagata Y, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: - Pages: -
  • DOI: 10.1007/s12328-020-01093-9.
  • Peer Reviewed / Open Access
• [Journal Article] Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability. (2020)
  • Author(s): Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Kodama K, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Clin J Gastroenterol. Volume: - Pages: -
  • DOI: 10.1007/s12328-020-01099-3.
  • Peer Reviewed / Open Access
• [Journal Article] Publisher Correction: Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP. (2020)
  • Author(s): Makokha GN, Abe-Chayama H, Chowdhury S, Hayes CN, Tsuge M, Yoshima T, Ishida Y, Zhang Y, Uchida T, Tateno C, Akiyama R, Chayama K.
  • Journal Title: Sci Rep. Volume: 10 Pages: 2233
  • DOI: 10 2233 10.1038/s41598-020-58888-6.
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: J Gastroenterol. Volume: - Pages: -
  • DOI: 10.1007/s00535-020-01672-0.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incidence of microsatellite instability-high hepatocellular carcinoma among Japanese patients and response to pembrolizumab. (2020)
  • Author(s): Kawaoka T, Ando Y, Yamauchi M, Suehiro Y, Yamaoka K, Kosaka Y, Fuji Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Ono A, Murakami E, Takahashi S, Tsuge M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Hepatol Res. Volume: - Pages: -
  • DOI: 10.1111/hepr.13496.
  • Peer Reviewed / Open Access
• [Journal Article] Serum miR-379 expression is related to the development and progression of hypercholesterolemia in non-alcoholic fatty liver disease. (2020)
  • Author(s): Okamoto K, Koda M, Okamoto T, Onoyama T, Miyoshi K, Kishina M, Matono T, Kato J, Tokunaga S, Sugihara T, Hiramatsu A, Hyogo H, Tobita H, Sato S, Kawanaka M, Hara Y, Hino K, Chayama K, Murawaki Y, Isomoto H.
  • Journal Title: PLoS One. Volume: 15 Pages: e0219412
  • DOI: 10.1371/journal.pone.0219412.
  • Peer Reviewed / Open Access
• [Journal Article] Classification of primary liver cancer with immunosuppression mechanisms and correlation with genomic alterations. (2020)
  • Author(s): Fujita M, Yamaguchi R, Hasegawa T, Shimada S, Arihiro K, Hayashi S, Maejima K, Nakano K, Fujimoto A, Ono A, Aikata H, Ueno M, Hayami S, Tanaka H, Miyano S, Yamaue H, Chayama K, Kakimi K, Tanaka S, Imoto S, Nakagawa H.
  • Journal Title: EBioMedicine. Volume: 53 Pages: 102659
  • DOI: 10.1016/j.ebiom.2020.102659.
  • Peer Reviewed / Open Access
• [Journal Article] Diminished hepatic IFN response following HCV clearance triggers HBV reactivation in coinfection. (2020)
  • Author(s): Cheng X, Uchida T, Xia Y, Umarova R, Liu CJ, Chen PJ, Gaggar A, Suri V, Mucke MM, Vermehren J, Zeuzem S, Teraoka Y, Osawa M, Aikata H, Tsuji K, Mori N, Hige S, Karino Y, Imamura M, Chayama K, Liang TJ.
  • Journal Title: J Clin Invest. Volume: - Pages: -
  • DOI: 10.1172/JCI135616.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Targeting clinical epigenetic reprogramming for chemoprevention of metabolic and viral hepatocellular carcinoma. (2020)
  • Author(s): Juhling F, Hamdane N, Crouchet E, Li S, El Saghire H, Mukherji A, Fujiwara N, Oudot MA, Thumann C, Saviano A, Roca Suarez AA, Goto K, Masia R, Sojoodi M, Arora G, Aikata H, Ono A, Tabrizian P, Schwartz M, Polyak SJ, Davidson I, Schmidl C, Chayama K, et al.
  • Journal Title: Gut. Volume: - Pages: -
  • DOI: 10.1136/gutjnl-2019-318918.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy. (2019)
  • Author(s): Nagaoki Y, Imamura M, Nishida Y, Daijo K, Teraoka Y, Honda F, Nakamura Y, Morio K, Fujino H, Nakahara T, Kawaoka T, Tsuge M, Hiramatsu A, Kawakami Y, Miki D, Hiyama Y, Ochi H, Chayama K, Aikata H.
  • Journal Title: J Med Virol. Volume: 91 Pages: 650-658
  • DOI: 10.1002/jmv.25352.
  • Peer Reviewed / Open Access
• [Journal Article] A nationwide survey on non-B, non-C hepatocellular carcinoma in Japan: 2011-2015 update. (2019)
  • Author(s): Tateishi R, Uchino K, Fujiwara N, Takehara T, Okanoue T, Seike M, Yoshiji H, Yatsuhashi H, Shimizu M, Torimura T, Moriyama M, Sakaida I, Okada H, Chiba T, Chuma M, Nakao K, Isomoto H, Sasaki Y, Kaneko S, Masaki T, Chayama K, Koike K.
  • Journal Title: J Gastroenterol. Volume: 54 Pages: 367-376
  • DOI: 10.1007/s00535-018-1532-5.
  • Peer Reviewed / Open Access
• [Journal Article] HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease. (2019)
  • Author(s): Fujii H, Imajo K, Yoneda M, Nakahara T, Hyogo H, Takahashi H, Hara T, Tanaka S, Sumida Y, Eguchi Y, Chayama K, Nakajima A, Nishimoto N, Kawada N; Japan Study Group of Nonalcoholic Fatty Liver Disease.
  • Journal Title: J Gastroenterol Hepatol. Volume: 34 Pages: 1390-1395
  • DOI: 10.1111/jgh.14595.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis. (2019)
  • Author(s): Kodama K, Kawaguchi T, Hyogo H, Nakajima T, Ono M, Seike M, Takahashi H, Nozaki Y, Kawanaka M, Tanaka S, Imajo K, Sumida Y, Kamada Y, Fujii H, Seko Y, Takehara T, Itoh Y, Nakajima A, Masaki N, Torimura T, Saibara T, Karino Y, Chayama K, Tokushige K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 34 Pages: 1626-1632
  • DOI: 10.1111/jgh.14608.
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous transvenous shunt occlusion for portosystemic encephalopathy due to lenvatinib administration to a patient with hepatocellular carcinoma and portosystemic shunt. (2019)
  • Author(s): Namba M, Kawaoka T, Aikata H, Kodama K, Uchikawa S, Ohya K, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Baba Y, Awai K, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: 12 Pages: 341-346
  • DOI: 10.1007/s12328-019-00938-2.
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of intracellular responses between HBV genotype A and C infection in human hepatocyte chimeric mice. (2019)
  • Author(s): Tsushima K, Tsuge M, Hiraga N, Uchida T, Murakami E, Makokha GN, Kurihara M, Nomura M, Hiyama Y, Fujino H, Ono A, Nakahara T, Yamauchi M, Abe-Chayama H, Kawaoka T, Miki D, Imamura M, Aikata H, Hayes CN, Chayama K.
  • Journal Title: J Gastroenterol. Volume: 54 Pages: 650-659
  • DOI: 10.1007/s00535-019-01558-w.
  • Peer Reviewed / Open Access
• [Journal Article] Reply: Hepatectomy versus stereotactic body radiotherapy for primary early hepatocellular carcinoma: A propensity -matched analysis in a single institution. (2019)
  • Author(s): Nakano R, Ohira M, Kobayashi T, Ide K, Tahara H, Kuroda S, Shimizu S, Kimura T, Nagata Y, Aikata H, Chayama K, Ohdan H.
  • Journal Title: Surgery. Volume: 165 Pages: 1054-1057
  • DOI: 10.1016/j.surg.2018.10.022.
  • Peer Reviewed / Open Access
• [Journal Article] HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response. (2019)
  • Author(s): Hamdane N, Juhling F, Crouchet E, El Saghire H, Thumann C, Oudot MA, Bandiera S, Saviano A, Ponsolles C, Roca Suarez AA, Li S, Fujiwara N, Ono A, Davidson I, Bardeesy N, Schmidl C, Bock C, Schuster C, Lupberger J, Habersetzer F, Doffoel M, Piardi T, Sommacale D, Imamura M, Chayama K. et al.
  • Journal Title: Gastroenterology. Volume: 156 Pages: 2313-2329.e7
  • DOI: 10.1053/j.gastro.2019.02.038.
  • Peer Reviewed / Open Access
• [Journal Article] Real-world virological efficacy and safety of daclatasvir/asunaprevir/beclabuvir in patients with chronic hepatitis C virus genotype 1 infection in Japan. (2019)
  • Author(s): Takaguchi K, Toyoda H, Tsutsui A, Suzuki Y, Nakamuta M, Imamura M, Senoh T, Nagano T, Tada T, Tachi Y, Hiraoka A, Michitaka K, Shibata H, Joko K, Okubo H, Tsuji K, Takaki S, Watanabe T, Ogawa C, Chayama K, Kumada T, Kudo M, Kumada H.
  • Journal Title: J Gastroenterol. Volume: 54 Pages: 742-751
  • DOI: 10.1007/s00535-019-01568-8.
  • Peer Reviewed / Open Access
• [Journal Article] Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection. (2019)
  • Author(s): Naganuma A, Chayama K, Notsumata K, Gane E, Foster GR, Wyles D, Kwo P, Crown E, Bhagat A, Mensa FJ, Otani T, Larsen L, Burroughs M, Kumada H.
  • Journal Title: J Gastroenterol. Volume: 54 Pages: 752-761
  • DOI: 10.1007/s00535-019-01569-7.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development. (2019)
  • Author(s): Lupberger J, Croonenborghs T, Roca Suarez AA, Van Renne N, Juhling F, Oudot MA, Virzi A, Bandiera S, Jamey C, Meszaros G, Brumaru D, Mukherji A, Durand SC, Heydmann L, Verrier ER, El Saghire H, Hamdane N, Bartenschlager R, Fereshetian S, Ramberger E, Sinha R, Nabian M, Chayama K. et al.
  • Journal Title: Gastroenterology. Volume: 157 Pages: 537-551.e9
  • DOI: 10.1053/j.gastro.2019.04.003.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes. (2019)
  • Author(s): Xue R, Chen L, Zhang C, Fujita M, Li R, Yan SM, Ong CK, Liao X, Gao Q, Sasagawa S, Li Y, Wang J, Guo H, Huang QT, Zhong Q, Tan J, Qi L, Gong W, Hong Z, Li M, Zhao J, Peng T, Lu Y, Lim KHT, Boot A, Ono A, Chayama K, Zhang Z, Rozen SG, Teh BT, Wang XW, Nakagawa H, Zeng MS, Bai F, Zhang N.
  • Journal Title: Cancer Cell. Volume: 35 Pages: 932-947.e8
  • DOI: 10.1016/j.ccell.2019.04.007.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis. (2019)
  • Author(s): Yen CJ, Yang ST, Chen RY, Huang W, Chayama K, Lee MH, Yang SJ, Lai HS, Yen HY, Hsiao YW, Wang JM, Lin YJ, Hung LY.
  • Journal Title: J Biomed Sci. Volume: 26 Pages: 44
  • DOI: 10.1186/s12929-019-0534-9.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP. (2019)
  • Author(s): Makokha GN, Abe-Chayama H, Chowdhury S, Hayes CN, Tsuge M, Yoshima T, Ishida Y, Zhang Y, Uchida T, Tateno C, Akiyama R, Chayama K
  • Journal Title: Sci Rep. Volume: 10 Pages: 2233
  • DOI: 10.1038/s41598-019-44934-5.
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of glecaprevir and pibrentasvir treatment for genotype 1b hepatitis C virus drug resistance-associated variants in humanized mice. (2019)
  • Author(s): Osawa M, Uchida T, Imamura M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Abe-Chayama H, Hayes CN, Makokha GN, Aikata H, Ishida Y, Tateno C, Miyayama Y, Hijikata M, Chayama K.
  • Journal Title: J Gen Virol. Volume: 100 Pages: 1123-1131
  • DOI: 10.1099/jgv.0.001268.
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib. (2019)
  • Author(s): Kodama K, Kawaoka T, Namba M, Uchikawa S, Ohya K, Morio K, Nakahara T, Murakami E, Yamauchi M, Hiramatsu A, Imamura M, Chayama K, Aikata H.
  • Journal Title: Oncology. Volume: 97 Pages: 75-81
  • DOI: 10.1159/000499715.
  • Peer Reviewed / Open Access
• [Journal Article] Management of HCV patients in cases of direct-acting antiviral failure. (2019)
  • Author(s): Hayes CN, Imamura M, Chayama K.
  • Journal Title: Expert Rev Gastroenterol Hepatol. Volume: 13 Pages: 839-848
  • DOI: 10.1080/17474124.2019.1651642.
  • Peer Reviewed / Open Access
• [Journal Article] Early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated by lenvatinib therapy. (2019)
  • Author(s): Ohya K, Kawaoka T, Namba M, Uchikawa S, Kodama K, Morio K, Nakahara T, Murakami E, Hiramatsu A, Tsuge M, Yamauchi M, Imamura M, Chayama K, Aikata H.
  • Journal Title: Sci Rep. Volume: 9 Pages: 12101
  • DOI: 10.1038/s41598-019-48045-z.
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of a self-management program in patients with chronic viral hepatitis in China. (2019)
  • Author(s): Cui Y, Moriyama M, Chayama K, Liu Y, Ya C, Muzembo BA, Rahman MM.
  • Journal Title: BMC Nurs. Volume: 18 Pages: 44
  • DOI: 10.1186/s12912-019-0366-7.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ribavirin induces hepatitis C virus genome mutations in chronic hepatitis patients who failed to respond to prior daclatasvir plus asunaprevir therapy. (2019)
  • Author(s): Saito Y, Imamura M, Uchida T, Osawa M, Teraoka Y, Fujino H, Nakahara T, Ono A, Murakami E, Kawaoka T, Miki D, Tsuge M, Serikawa M, Aikata H, Abe-Chayama H, Hayes CN, Chayama K.
  • Journal Title: J Med Virol. Volume: 92 Pages: 210-218
  • DOI: 10.1002/jmv.25602.
• [Journal Article] eVIDENCE: a practical variant filtering for low-frequency variants detection in cell-free DNA. (2019)
  • Author(s): Mizuno K, Akamatsu S, Sumiyoshi T, Wong JH, Fujita M, Maejima K, Nakano K, Ono A, Aikata H, Ueno M, Hayami S, Yamaue H, Chayama K, Inoue T, Ogawa O, Nakagawa H, Fujimoto A.
  • Journal Title: Sci Rep. Volume: 9 Pages: 15017
  • DOI: 10.1038/s41598-019-51459-4
  • Peer Reviewed / Open Access
• [Journal Article] Pruritus in patients with chronic liver disease and serum autotaxin levels in patients with primary biliary cholangitis. (2019)
  • Author(s): Fujino H, Tanaka M, Imamura M, Morio K, Ono A, Nakahara T, Murakami E, Kawaoka T, Takahashi S, Miki D, Tsuge M, Hiramatsu A, Aikata H, Hayes CN, Chayama K.
  • Journal Title: BMC Gastroenterol. Volume: 19 Pages: 169
  • DOI: 10.1186/s12876-019-1092-z
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Lipids in Hepatocellular Carcinoma. (2019)
  • Author(s): Hayes CN, Zhang P, Chayama K.
  • Journal Title: Hepatocellular Carcinoma. Volume: - Pages: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Isolated cardiac metastases of hepatocellular carcinoma after resection: a case report. (2019)
  • Author(s): Tamura Y, Kawaoka T, Aikata H, Namba M, Fujii Y, Morio K, Murakami E, Yamauchi M, Hiramatsu A, Nakahara T, Imamura M, Maruhashi T, Kobayashi T, Ohdan H, Kimura T, Nagata Y, Arihiro K, Chayama K.
  • Journal Title: Clin J Gastroenterol. Volume: - Pages: -
  • DOI: 10.1007/s12328-019-01075-6.
  • Peer Reviewed / Open Access
• [Journal Article] Comparative study on the replication of HCV1b genome between wild-type and cell culture-adaptive mutant in regard to sensitivities against anti-HCV drugs. (2019)
  • Author(s): Miyayama Y, Lee H, Song H, Abe-Chayama H, Miki D, Imamura M, Chayama K, Hijikata M.
  • Journal Title: Microbiol Immunol. Volume: - Pages: -
  • DOI: 10.1111/1348-0421.12768.
  • Peer Reviewed / Open Access
• [Journal Article] Sinusoidal obstruction syndrome post-treatment with trastuzumab emtansine (T-DM1) in advanced breast cancer. (2019)
  • Author(s): Fujii Y, Doi M, Tsukiyama N, Hattori Y, Ohya K, Shiroma N, Morio K, Morioka T, Aikata H, Shinozaki K, Chayama K.
  • Journal Title: Int Cancer Conf J. Volume: 9 Pages: 18-23
  • DOI: 10.1007/s13691-019-00392-4.
  • Peer Reviewed / Open Access
• [Presentation] HCV治療の今後の展望-ウイルス性肝炎撲滅を目指した最新治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第45回日本急性肝不全研究会
• [Presentation] HCV治療の今後の展望-ウイルス性肝炎撲滅を目指した最新治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第20回日本肝がん分子標的治療研究会
• [Presentation] 最新のC型肝炎、肝硬変の治療 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第33回日本臨床内科医学会
• [Presentation] ウイルス性肝炎研究の進歩と今後の課題 (2019)
  • Author(s): 茶山一彰
  • Organizer: 第23回日本肝臓学会大会
• [Presentation] 肝硬変診療の課題 (2019)
  • Author(s): 茶山一彰
  • Organizer: 日本消化器関連学会機構（JDDW）2019
• [Book] 肝原発平滑筋肉腫の一例 (2019)
  • Author(s): 山岡賢治, 児玉健一郎, 河岡友和, 難波麻衣子, 内川慎介, 大屋一輝, 盛生 慶, 中原隆志, 村上英介, 山内理海, 平松 憲, 今村道雄, 相方 浩, 織田麻琴, 有廣光司, 小林 剛, 大段秀樹, 茶山一彰
  • Total Pages: 358-365
  • Publisher: 肝臓
• [Remarks] 広島大学大学院 医系科学研究科 消化器・代謝内科学
  • URL: http://shounai.hiroshima-u.ac.jp/
• [Remarks] 広島大学 自立型研究拠点 肝臓・消化器研究拠点
  • URL: http://shounai.hiroshima-u.ac.jp/liverproject/
• [Patent(Industrial Property Rights)] Ｂ型肝炎治療用核酸分子 (2019)
  • Inventor(s): 茶山一彰/吉間忠彦/水谷隆之
  • Industrial Property Rights Holder: 茶山一彰/吉間忠彦/水谷隆之
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2019-514692