OTC欠損症のモデル動物作製とその応用

2014 Fiscal Year Annual Research Report

• Project/Area Number: 26670383
• Research Institution: Hiroshima University
• Principal Investigator: 茶山 一彰 広島大学, 医歯薬保健学研究院, 教授 (00211376)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: ゲノム

Outline of Annual Research Achievements

肝臓を疾患の主要臓器とする遺伝性疾患はα1 anti-trypsin欠損症、血友病、OTC欠損症、ウイルソン病、ヘモクロマトーシスなど多数存在する。これらの疾患の病態の解析、治療の開発にはノックアウトマウスが用いられていることが多い。しかし、マウスとヒトの病態は必ずしも同一ではなく、またマウスで良好なモデルが作製できないものもある。我々は肝臓がほぼ完全にヒト肝細胞に置換されたキメラマウスを作製して、ヒトとチンパンジーにしか感染しないB型肝炎ウイルス、C型肝炎ウイルスの感染モデルを作製し、創薬研究に成果を上げてきた。さらに、最近我々は理学研究科との共同研究でTALENやCRISPR/Casシステムを用いて複数の遺伝子を同時にknockoutする系を構築した。また、BacMamシステムを使用して、高効率にヒト肝細胞キメラマウス由来の培養ヒト肝細胞にGFP遺伝子を導入できることも確認した。
そこで、本研究ではこれらの技術を使用してヒト肝細胞キメラマウスの肝細胞の標的遺伝子をknockoutし、創薬研究が可能なマウス、細胞系を創出することとした。平成26年度にはOTC欠損症のモデル作製に必要なknockout constructを作製し、BacMamのシステムに導入した。現在BacMamシステムでマウス中のヒト肝細胞に遺伝子が導入し、実際に切断が得られるかどうかについて検討を行っている。
今後はこのようにして正常の遺伝子を破壊した細胞を選択し、さらにそれをキメラマウスに戻すことにより、全てのヒト肝細胞が遺伝子欠損を有する動物モデルを作製することが出来るが、さらにこの動物から取り出した肝臓を再潅流して播種することにより薬剤のスクリーニングに使用できる細胞を作製することが出来ると考えられるため、この方向でさらに研究を進めていく。

Research Products

• [Journal Article] Hepatitis C virus core protein suppresses mitophagy by interacting with parkin in the context of mitochondrial depolarization. (2014)
  • Author(s): Hara Y, Yanatori I, Ikeda M, Kiyokage E, Nishina S, Tomiyama Y, Toida K, Kishi F, Kato N, Imamura M, Chayama K, Hino K.
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  • Peer Reviewed
• [Journal Article] Interleukin 28B polymorphism predicts interferon plus ribavirin treatment outcome in patients with hepatitis C virus-related liver cirrhosis: A multicenter retrospective study in Japan. (2014)
  • Author(s): Shakado S, Sakisaka S, Okanoue T, Chayama K, Izumi N, Toyoda J, Tanaka E, Ido A, Takehara T, Yoshioka K, Hiasa Y, Nomura H, Seike M, Ueno Y, Kumada H.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 983-992
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  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of RECIST and tumor markers. (2014)
  • Author(s): Miyaki D, Kawaoka T, Aikata H, Kan H, Fujino H, Fukuhara T, Kobayashi T, Naeshiro N, Honda Y, Tsuge M, Hiramatsu A, Imamura M, Hyogo H, Kawakami Y, Yoshimatsu R, Yamagami T, Awai K, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 30 Pages: 726-32
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  • Peer Reviewed / Open Access
• [Journal Article] Impact of alloimmune T cell responses on hepatitis C virus replication in liver transplant recipients. (2014)
  • Author(s): Tanaka Y, Ohira M, Tashiro H, Imamura M, Chayama K, Ohdan H.
  • Journal Title: Hum Immunol. Volume: 75 Pages: 1259-1267
  • DOI: 10.1016/j.humimm.2014.09.006.
  • Peer Reviewed
• [Journal Article] Emerging treatments for chronic hepatitis C. (2014)
  • Author(s): Hayes CN, Chayama K.
  • Journal Title: J Formos Med Assoc. Volume: 114 Pages: 204-215
  • DOI: 10.1016/j.jfma.2014.09.001.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Case reports of portal vein thrombosis and bile duct stenosis after stereotactic body radiation therapy for hepatocellular carcinoma. (2014)
  • Author(s): Takahashi S, Kimura T, Kenjo M, Nishibuchi I, Takahashi I, Takeuchi Y, Doi Y, Kaneyasu Y, Murakami Y, Honda Y, Aikata H, Chayama K, Nagata Y.
  • Journal Title: Hepatol Res. Volume: 44 Pages: E273-278
  • DOI: 10.1111/hepr.12241. Epub 2014 Jan 8.
  • Peer Reviewed / Open Access
• [Journal Article] Differences in K- ras and mitochondrial DNA mutations and microsatellite instability between colorectal cancers of Vietnamese and Japanese patients. (2014)
  • Author(s): Miwata T, Hiyama T, Quach D, Le H, Hua H, Oka S, Tanaka S, Arihiro K, Chayama K.
  • Journal Title: BMC Gastroenterol. Volume: 14 Pages: 203
  • DOI: 10.1186/s12876-014-0203-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differences in serum microRNA profiles in hepatitis B and C virus infection. (2014)
  • Author(s): Akamatsu S, Hayes CN, Tsuge M, Miki D, Akiyama R, Ochi H, Hiraga N, Imamura M, Aikata H, Kawaoka T, Kawakami Y, Chayama PK.
  • Journal Title: J Infect. Volume: 70 Pages: 273-87
  • DOI: 10.1016/j.jinf.2014.10.017.
  • Peer Reviewed
• [Journal Article] Endocannabinoid CB1 antagonists inhibit hepatitis C virus production, providing a novel class of antiviral host-targeting agents. (2014)
  • Author(s): Shahidi M, Tay ES, Read SA, Ramezani-Moghadam M, Chayama K, George J, Douglas MW.
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• [Journal Article] Upper limit of normal serum alanine aminotransferase levels in Japanese subjects. (2014)
  • Author(s): Tanaka K, Hyogo H, Ono M, Takahashi H, Kitajima Y, Ono N, Eguchi T, Fujimoto K, Chayama K, Saibara T, Anzai K, Eguchi Y, Japan Study Group of Non-alcoholic Fatty Liver D.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 1196-1207
  • DOI: 10.1111/hepr.12293.
  • Peer Reviewed / Open Access
• [Journal Article] Type 2 diabetes mellitus is associated with the fibrosis severity in patients with nonalcoholic fatty liver disease in a large retrospective cohort of Japanese patients. (2014)
  • Author(s): Nakahara T, Hyogo H, Yoneda M, Sumida Y, Eguchi Y, Fujii H, Ono M, Kawaguchi T, Imajo K, Aikata H, Tanaka S, Kanemasa K, Fujimoto K, Anzai K, Saibara T, Sata M, Nakajima A, Itoh Y, Chayama K, Okanoue T, Japan Study Group of Nonalcoholic Fatty Liver D.
  • Journal Title: J Gastroenterol. Volume: 49 Pages: 1477-1484
  • DOI: 10.1007/s00535-013-0911-1.
  • Peer Reviewed / Open Access
• [Journal Article] Stereotactic body radiotherapy for patients with small hepatocellular carcinoma ineligible for resection or ablation therapies. (2014)
  • Author(s): Kimura T, Aikata H, Takahashi S, Takahashi I, Nishibuchi I, Doi Y, Kenjo M, Murakami Y, Honda Y, Kakizawa H, Awai K, Chayama K, Nagata Y.
  • Journal Title: Hepatol Res. Volume: 45 Pages: 378-86
  • DOI: 10.1111/hepr.12359.
  • Peer Reviewed / Open Access
• [Journal Article] Effect of vitamin D supplementation on pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b: a randomized controlled trial. (2014)
  • Author(s): Yokoyama S, Takahashi S, Kawakami Y, Hayes CN, Kohno H, Kohno H, Tsuji K, Aisaka Y, Kira S, Yamashina K, Nonaka M, Moriya T, Kitamoto M, Aimitsu S, Nakanishi T, Kawakami H, Chayama K.
  • Journal Title: J Viral Hepat. Volume: 21 Pages: 348-356
  • DOI: 10.1111/jvh.12146.
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcome of patients with gastric varices treated by balloon-occluded retrograde transvenous obliteration. (2014)
  • Author(s): Naeshiro N, Aikata H, Kakizawa H, Hyogo H, Kan H, Fujino H, Kobayashi T, Fukuhara T, Honda Y, Ohno A, Miyaki D, Kawaoka T, Tsuge M, Hiraga N, Hiramatsu A, Imamura M, Kawakami Y, Takahashi S, Awai K, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 29 Pages: 1035-1042
  • DOI: 10.1111/jgh.12508.
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of sitagliptin for the treatment of nonalcoholic fatty liver disease with type 2 diabetes mellitus. (2014)
  • Author(s): Fukuhara T, Hyogo H, Ochi H, Fujino H, Kan H, Naeshiro N, Honda Y, Miyaki D, Kawaoka T, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Aikata H, Chayama K.
  • Journal Title: Hepatogastroenterology. Volume: 61 Pages: 323-328
  • Peer Reviewed
• [Journal Article] Non-invasive assessment of liver steatosis in non-alcoholic fatty liver disease. (2014)
  • Author(s): Kan H, Kimura Y, Hyogo H, Fukuhara T, Fujino H, Naeshiro N, Honda Y, Kawaoka T, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Aikata H, Ochi H, Arihiro K, Chayama K.
  • Journal Title: Hepatol Res. Volume: 44 Pages: E420-427
  • DOI: 10.1111/hepr.12330.
  • Peer Reviewed / Open Access
• [Journal Article] IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population. (2014)
  • Author(s): Ochi H, Miki D, Hayes CN, Abe H, Hayashida Y, Kubo M, Chayama K.
  • Journal Title: J Gen Virol. Volume: 95 Pages: 1297-1306
  • DOI: 10.1099/vir.0.060103-0.
  • Peer Reviewed
• [Journal Article] The association of insomnia with gastroesophageal reflux symptoms in biopsy-proven nonalcoholic fatty liver disease. (2014)
  • Author(s): Taketani H, Sumida Y, Tanaka S, Imajo K, Yoneda M, Hyogo H, Ono M, Fujii H, Eguchi Y, Kanemasa K, Chayama K, Itoh Y, Yoshikawa T, Saibara T, Fujimoto K, Nakajima A, Japan Study Group of N.
  • Journal Title: J Gastroenterol. Volume: 49 Pages: 1163-1174
  • DOI: 10.1007/s00535-013-0871-5.
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous transvenous embolization for portosystemic shunts associated with encephalopathy: Long-term outcomes in 14 patients. (2014)
  • Author(s): Naeshiro N, Kakizawa H, Aikata H, Kan H, Fujino H, Fukuhara T, Kobayashi T, Honda Y, Miyaki D, Kawaoka T, Tsuge M, Hiramatsu A, Imamura M, Kawakami Y, Hyogo H, Ishikawa M, Awai K, Chayama K.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 740-749
  • DOI: 10.1111/hepr.12181.
  • Peer Reviewed / Open Access
• [Journal Article] Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. (2014)
  • Author(s): Honda Y, Kimura T, Aikata H, Nakahara T, Naeshiro N, Tanaka M, Miyaki D, Nagaoki Y, Kawaoka T, Takaki S, Hiramatsu A, Waki K, Ishikawa M, Kakizawa H, Kenjo M, Awai K, Nagata Y, Chayama K.
  • Journal Title: Hepatogastroenterology. Volume: 61 Pages: 31-36
  • Peer Reviewed
• [Journal Article] Virological escape in HCV genotype-1-infected patients receiving daclatasvir plus ribavirin and peginterferon alfa-2a or alfa-2b. (2014)
  • Author(s): McPhee F, Hernandez D, Zhou N, Yu F, Ueland J, Monikowski A, Chayama K, Toyota J, Izumi N, Yokosuka O, Kawada N, Osaki Y, Hughes EA, Watanabe H, Ishikawa H, Kumada H.
  • Journal Title: Antivir Ther. Volume: 19 Pages: 479-490
  • DOI: 10.3851/IMP2729.
  • Peer Reviewed
• [Journal Article] Quantitative effect of natural killer-cell licensing on hepatocellular carcinoma recurrence after curative hepatectomy. (2014)
  • Author(s): Tanimine N, Tanaka Y, Kobayashi T, Tashiro H, Miki D, Imamura M, Aikata H, Tanaka J, Chayama K, Ohdan H.
  • Journal Title: Cancer Immunol Res. Volume: 2 Pages: 1142-1147
  • DOI: 10.1158/2326-6066.CIR-14-0091.
  • Peer Reviewed / Open Access
• [Journal Article] Predictive value of the IFNL4 polymorphism on outcome of telaprevir, peginterferon, and ribavirin therapy for older patients with genotype 1b chronic hepatitis C. (2014)
  • Author(s): Fujino H, Imamura M, Nagaoki Y, Kawakami Y, Abe H, Hayes CN, Kan H, Fukuhara T, Kobayashi T, Masaki K, Ono A, Nakahara T, Honda Y, Naeshiro N, Urabe A, Yokoyama S, Miyaki D, Murakami E, Kawaoka T, Hiraga N, Tsuge M, Hiramatsu A, Hyogo H, Aikata H, Takahashi S, Miki D, Ochi H, Ohishi W, Chayama K
  • Journal Title: J Gastroenterol. Volume: 49 Pages: 1548-1556
  • DOI: 10.1007/s00535-013-0924-9.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The effects of bisphosphonate zoledronic acid in hepatocellular carcinoma, depending on mevalonate pathway. (2014)
  • Author(s): Honda Y, Takahashi S, Zhang Y, Ono A, Murakami E, Shi N, Kawaoka T, Miki D, Tsuge M, Hiraga N, Abe H, Ochi H, Imamura M, Aikata H, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 30 Pages: 619-27
  • DOI: 10.1111/jgh.12715.
  • Peer Reviewed / Open Access
• [Journal Article] Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease. (2014)
  • Author(s): Kessoku T, Ogawa Y, Yoneda M, Imajo K, Sumida Y, Eguchi Y, Fujii H, Hyogo H, Ono M, Suzuki Y, Kawaguchi T, Chayama K, Tanaka S, Fujimoto K, Anzai K, Saibara T, Sata M, Itoh Y, Nakajima A, Okanoue T, Japan Study Group of N.
  • Journal Title: World J Gastroenterol. Volume: 20 Pages: 10108-10114
  • DOI: 10.3748/wjg.v20.i29.10108.
  • Peer Reviewed / Open Access
• [Journal Article] Interferon lambda 4 polymorphism affects on outcome of telaprevir, pegylated interferon and ribavirin combination therapy for chronic hepatitis C. (2014)
  • Author(s): Nagaoki Y, Imamura M, Kawakami Y, Kan H, Fujino H, Fukuhara T, Kobayashi T, Ono A, Nakahara T, Naeshiro N, Urabe A, Yokoyama S, Miyaki D, Murakami E, Kawaoka T, Tsuge M, Hiramatsu A, Aikata H, Takahashi S, Hayes CN, Ochi H, Chayama K, Hiroshima Liver Study G.
  • Journal Title: Hepatol Res. Volume: 44 Pages: E447-454
  • DOI: 10.1111/hepr.12336.
  • Peer Reviewed / Open Access
• [Journal Article] New insight into the enhanced effect of pegylated interferon-alpha. (2014)
  • Author(s): Abe H, Hayes CN, Chayama K.
  • Journal Title: Hepatology. Volume: 60 Pages: 1435-1437
  • DOI: 10.1002/hep.27269.
  • Peer Reviewed / Open Access
• [Journal Article] Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA. (2014)
  • Author(s): Kohno T, Tsuge M, Murakami E, Hiraga N, Abe H, Miki D, Imamura M, Ochi H, Hayes CN, Chayama K.
  • Journal Title: J Viral Hepat. Volume: 21 Pages: e89-97
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits. (2014)
  • Author(s): Kitamoto A, Kitamoto T, Nakamura T, Ogawa Y, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Nakao K, Sekine A, Chayama K, Nakajima A, Hotta K.
  • Journal Title: Endocr J. Volume: 61 Pages: 683-689
  • Peer Reviewed / Open Access
• [Journal Article] Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. (2014)
  • Author(s): Kumada H, Suzuki Y, Ikeda K, Toyota J, Karino Y, Chayama K, Kawakami Y, Ido A, Yamamoto K, Takaguchi K, Izumi N, Koike K, Takehara T, Kawada N, Sata M, Miyagoshi H, Eley T, McPhee F, Damokosh A, Ishikawa H, Hughes E.
  • Journal Title: Hepatology. Volume: 59 Pages: 2083-2091
  • DOI: 10.1002/hep.27113.
  • Peer Reviewed / Open Access
• [Journal Article] Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease. (2014)
  • Author(s): Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Nakao K, Sekine A, Chayama K, Nakajima A, Hotta K.
  • Journal Title: J Hum Genet. Volume: 59 Pages: 241-246
  • DOI: 10.1038/jhg.2014.17.
  • Peer Reviewed
• [Journal Article] Ultradeep sequencing study of chronic hepatitis C virus genotype 1 infection in patients treated with daclatasvir, peginterferon, and ribavirin. (2014)
  • Author(s): Murakami E, Imamura M, Hayes CN, Abe H, Hiraga N, Honda Y, Ono A, Kosaka K, Kawaoka T, Tsuge M, Aikata H, Takahashi S, Miki D, Ochi H, Matsui H, Kanai A, Inaba T, McPhee F, Chayama K.
  • Journal Title: Antimicrob Agents Chemother. Volume: 58 Pages: 2105-2112
  • DOI: 10.1128/AAC.02068-13.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial. (2014)
  • Author(s): Ishigaki T, Sasaki T, Serikawa M, Minami T, Okazaki A, Yukutake M, Ishii Y, Kosaka K, Mouri T, Yoshimi S, Chayama K.
  • Journal Title: J Gastroenterol Hepatol. Volume: 29 Pages: 653-659
  • DOI: 10.1111/jgh.12427.
  • Peer Reviewed / Open Access
• [Journal Article] Transarterial therapy of hepatocellular carcinoma fed by the right renal capsular artery. (2014)
  • Author(s): Ishikawa M, Yamagami T, Kakizawa H, Hieda M, Toyota N, Fukumoto W, Kajiwara K, Yoshimatsu R, Aikata H, Chayama K, Awai K.
  • Journal Title: J Vasc Interv Radiol. Volume: 25 Pages: 389-395
  • DOI: 10.1016/j.jvir.2013.11.009.
  • Peer Reviewed
• [Journal Article] Aryl hydrocarbon receptor plays protective roles in ConA-induced hepatic injury by both suppressing IFN-gamma expression and inducing IL-22. (2014)
  • Author(s): Abe H, Kimura A, Tsuruta S, Fukaya T, Sakaguchi R, Morita R, Sekiya T, Shichita T, Chayama K, Fujii-Kuriyama Y, Yoshimura A.
  • Journal Title: Int Immunol. Volume: 26 Pages: 129-137
  • DOI: 10.1093/intimm/dxt049.
  • Peer Reviewed / Open Access
• [Journal Article] Non-invasive liver fibrosis score calculated by combination of virtual touch tissue quantification and serum liver functional tests in chronic hepatitis C patients. (2014)
  • Author(s): Takaki S, Kawakami Y, Miyaki D, Nakahara T, Naeshiro N, Murakami E, Tanaka M, Honda Y, Yokoyama S, Nagaoki Y, Kawaoka T, Hiramatsu A, Tsuge M, Hiraga N, Imamura M, Hyogo H, Aikata H, Takahashi S, Arihiro K, Chayama K.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 280-287
  • DOI: 10.1111/hepr.12129.
  • Peer Reviewed / Open Access
• [Journal Article] Long-term elimination of hepatitis C virus from human hepatocyte chimeric mice after interferon-gamma gene transfer. (2014)
  • Author(s): Takahashi Y, Ando M, Nishikawa M, Hiraga N, Imamura M, Chayama K, Takakura Y.
  • Journal Title: Hum Gene Ther Clin Dev. Volume: 25 Pages: 28-39
  • DOI: 10.1089/humc.2013.066.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical outcome and prognostic factors of patients with hepatocellular carcinoma and extrahepatic metastasis treated with sorafenib. (2014)
  • Author(s): Kawaoka T, Aikata H, Kan H, Fujino H, Fukuhara T, Kobayashi T, Naeshiro N, Miyaki D, Hiramatsu A, Imamura M, Kawakami Y, Hyogo H, Chayama K.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 1320-1328
  • DOI: 10.1111/hepr.12307.
  • Peer Reviewed / Open Access
• [Journal Article] Letter: Pitavastatin supplementation of PEG-IFN/ribavirin improves sustained virological response against HCV. (2014)
  • Author(s): Yokoyama S, Kawakami Y, Chayama K.
  • Journal Title: Aliment Pharmacol Ther. Volume: 39 Pages: 443-444
  • DOI: 10.1111/apt.12605.
  • Peer Reviewed / Open Access
• [Journal Article] Serum asymmetric dimethylarginine levels are independently associated with procollagen III N-terminal peptide in nonalcoholic fatty liver disease patients. (2014)
  • Author(s): Hyogo H, Yamagishi S, Maeda S, Fukami K, Ueda S, Okuda S, Nakahara T, Kimura Y, Ishitobi T, Chayama K.
  • Journal Title: Clin Exp Med. Volume: 14 Pages: 45-51
  • DOI: 10.1007/s10238-012-0223-4.
  • Peer Reviewed / Open Access
• [Journal Article] A randomized trial of daclatasvir with peginterferon alfa-2b and ribavirin for HCV genotype 1 infection. (2014)
  • Author(s): Suzuki F, Toyota J, Ikeda K, Chayama K, Mochida S, Hayashi N, Ishikawa H, Miyagoshi H, Hu W, McPhee F, Hughes EA, Kumada H.
  • Journal Title: Antivir Ther. Volume: 19 Pages: 491-499
  • DOI: 10.3851/IMP2730
  • Peer Reviewed
• [Journal Article] Two patients treated with pegylated interferon/ribavirin/telaprevir triple therapy for recurrent hepatitis C after living donor liver transplantation. (2014)
  • Author(s): Kawaoka T, Takahashi S, Tatsukawa Y, Hiramatsu A, Hiraga N, Miki D, Tsuge M, Imamura M, Kawakami Y, Aikata H, Ochi H, Ishiyama K, Ide K, Tashiro H, Ohdan H, Chayama K.
  • Journal Title: Hepatol Res. Volume: 44 Pages: 1259-1264
  • DOI: 10.1111/hepr.12296.
  • Peer Reviewed / Open Access
• [Journal Article] Serum interleukin-6 associated with hepatocellular carcinoma risk: a nested case-control study. (2014)
  • Author(s): Ohishi W, Cologne JB, Fujiwara S, Suzuki G, Hayashi T, Niwa Y, Akahoshi M, Ueda K, Tsuge M, Chayama K.
  • Journal Title: Int J Cancer. Volume: 134 Pages: 154-163
  • DOI: 10.1002/ijc.28337.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nonalcoholic fatty liver disease and cardiovascular disease. (2014)
  • Author(s): Hyogo H, Chayama K, Yamagishi S.
  • Journal Title: Curr Pharm Des. Volume: 20 Pages: 2403-2411
  • DOI: 10.2174/13816128113199990476
  • Peer Reviewed
• [Journal Article] Multiplex genome engineering in human cells using all-in-one CRISPR/Cas9 vector system. (2014)
  • Author(s): Sakuma T, Nishikawa A, Kume S, Chayama K, Yamamoto T.
  • Journal Title: Sci Rep. Volume: 4 Pages: 5400
  • DOI: 10.1038/srep05400.
  • Peer Reviewed / Open Access
• [Journal Article] Telaprevir is effective given every 12 h at 750 mg with pegylated interferon-alpha2b and ribavirin to Japanese patients with HCV-1b IL28B rs8099917 TT. (2014)
  • Author(s): Kawakami Y, Suzuki F, Karino Y, Toyota J, Kumada H, Chayama K.
  • Journal Title: Antivir Ther. Volume: 19 Pages: 277-285
  • DOI: 10.3851/IMP2706.
  • Peer Reviewed
• [Journal Article] Smoking cessation reverses DNA double-strand breaks in human mononuclear cells. (2014)
  • Author(s): Ishida M, Ishida T, Tashiro S, Uchida H, Sakai C, Hironobe N, Miura K, Hashimoto Y, Arihiro K, Chayama K, Kihara Y, Yoshizumi M.
  • Journal Title: PLoS One. Volume: 9 Pages: e103993
  • DOI: 10.1371/journal.pone.0103993.
  • Peer Reviewed / Open Access
• [Journal Article] Hepatitis C virus (HCV) reactivation caused by steroid therapy for dermatomyositis. (2014)
  • Author(s): Mori N, Imamura M, Takaki S, Araki T, Hayes NC, Aisaka Y, Chayama K.
  • Journal Title: Intern Med. Volume: 53 Pages: 2689-2693
  • DOI: 10.2169/internalmedicine.53.3194
  • Peer Reviewed / Open Access
• [Journal Article] Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. (2014)
  • Author(s): Shiraishi Y, Fujimoto A, Furuta M, Tanaka H, Chiba K, Boroevich KA, Abe T, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Shibuya T, Nakano K, Sasaki A, Maejima K, Kitada R, Hayami S, Shigekawa Y, Marubashi S, Yamada T, Kubo M, Ishikawa O, Aikata H, Arihiro K, Ohdan H, Yamamoto M, Yamaue H, Chayama K
  • Journal Title: PLoS One. Volume: 9 Pages: e114263
  • DOI: 10.1371/journal.pone.0114263.
  • Peer Reviewed / Open Access
• [Presentation] Hepatitis B mouse model involving CTL (2015)
  • Author(s): 茶山一彰
  • Organizer: 肝炎部会
  • Place of Presentation: 台北（台湾）
  • Year and Date: 2015-01-25 – 2015-01-25
• [Presentation] 肝硬変の新たなマネージメント (2014)
  • Author(s): 茶山一彰
  • Organizer: 第102回日本消化器病学会中国支部例会
  • Place of Presentation: 広島
  • Year and Date: 2014-11-29 – 2014-11-29
• [Presentation] All-oral Dual Combination of Daclatasvir plus Asunaprevir Compared with Telaprevir plus Peginterferon Alfa/Ribavirin in Treatment-maive Japanese Patients ChronicallyInfected with HCV Genotype 1b:Results from a Phase 3 Study (2014)
  • Author(s): 茶山一彰
  • Organizer: The 65nd Annual Meeting of American Association for the Study of Liver Diseases 2014(AASLD)
  • Place of Presentation: ボストン(アメリカ)
  • Year and Date: 2014-11-11 – 2014-11-11
• [Presentation] 肝炎ウイルス感染と肝細胞癌 (2014)
  • Author(s): 茶山一彰
  • Organizer: 日本消化器関連学会機構(JDDW)2014
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-26 – 2014-10-26
• [Presentation] 肝動脈化学塞栓療法の新しい治療戦略 (2014)
  • Author(s): 茶山一彰
  • Organizer: JDDW2014第18回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-24 – 2014-10-24
• [Presentation] C型肝炎治療の新展開と到達点 (2014)
  • Author(s): 茶山一彰
  • Organizer: JDDW2014第18回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2014-10-23 – 2014-10-24
• [Presentation] 肝癌に対する経カテーテル治療におけるDEB-TACEの位置づけ (2014)
  • Author(s): 茶山一彰
  • Organizer: 第21回日本門脈圧亢進症学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-13 – 2014-09-13
• [Presentation] C型慢性肝炎に対する治療の最前線 (2014)
  • Author(s): 茶山一彰
  • Organizer: 日本内科学会北陸支部 第62回生涯教育講演会
  • Place of Presentation: 金沢
  • Year and Date: 2014-06-22 – 2014-06-22
• [Presentation] C型肝炎撲滅に向けた治療戦略 (2014)
  • Author(s): 茶山一彰
  • Organizer: 第101回日本消化器病学会中国支部例会
  • Place of Presentation: 岡山
  • Year and Date: 2014-06-21 – 2014-06-21
• [Presentation] 講演1：DC Beadによる肝動脈化学塞栓療法 講演2：肝癌治療におけるイノベーション (2014)
  • Author(s): 茶山一彰
  • Organizer: 第50回日本肝癌研究会
  • Place of Presentation: 京都
  • Year and Date: 2014-06-05 – 2014-06-05
• [Presentation] C型肝炎に対する最新の治療 (2014)
  • Author(s): 茶山一彰
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-29
• [Presentation] 肝炎ウイルスに対する創薬研究 (2014)
  • Author(s): 茶山一彰
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-29 – 2014-05-29
• [Presentation] プロテアーゼ阻害剤の知見と問題点 (2014)
  • Author(s): 茶山一彰
  • Organizer: 第100回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24 – 2014-04-24
• [Remarks] 広島大学病院消化器・代謝内科ホームページ
  • URL: http://home.hiroshima-u.ac.jp/naika1/research_profile/liver_lab/
• [Patent(Industrial Property Rights)] 急性重症肝炎モデル非ヒト動物の作製方法、急性重症肝炎モデル非ヒト動物、劇症肝炎治療薬のスクリーニング方法および劇症肝炎治療薬 (2014)
  • Inventor(s): 茶山一彰
  • Industrial Property Rights Holder: 茶山一彰
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2014-217516
  • Filing Date: 2014-10-24