• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The analysis of IFN-lambda related innate immunity and the mechanism of immne escape of HBV using human induced pluripotent stem cell-derived hepatic cell lines.

Research Project

Project/Area Number 17K15931
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MURAKAWA Miyako  東京医科歯科大学, 医学部附属病院, 助教 (20733851)

Research Collaborator ASANIHA Yasuhiro  
KAKINUMA Sei  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsインターフェロンラムダ / ウイルス性肝炎 / 発癌 / B型肝炎 / IFNλ / ウイルス / 免疫 / iPS細胞
Outline of Final Research Achievements

We investigated the role of IFN-λ on chronic viral hepatitis using both human induced pluripotent stem cell-derived hepatic cell lines and liver biopsy samples, blood samples, and clinical data obtained from the patients with viral hepatitis. The difference of anti-viral effect and expression of ISGs according to the expression levels of IFNL were shown in our study. Moreover, we found that the risk for HCC development were high in the patients under the antiviral treatment with higher expression levels of serum IFN-λ3. Additionally, by the sub-analysis of HBV clinical data, we confirmed the relationship between diabetes mellitus and HCC development in the patients in whom HBV replication were suppressed well.

Academic Significance and Societal Importance of the Research Achievements

今回、新規抗HBV治療薬の開発に直結する成果は得られなかったが、IFNλの機能には未だ不明点が多い中で、ウイルスが駆除された状況でもIFNλ3が誘導され、かつその後の発癌とも関連するという新たな知見は、今後問題となり続ける抗ウイルス治療後発癌に対する治療戦略における新たなターゲットを見出せた点で有意義である。また、IFNλ3の抗HBV作用について臨床データを用いた再検証を行う中で、現在急増している糖尿病がHBV肝癌に関わることを示したことは、癌健診の啓蒙などの社会的意義も大きい。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (29 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 9 results,  Acknowledgement Compliant: 3 results) Presentation (18 results) (of which Int'l Joint Research: 6 results) Book (1 results)

  • [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

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 5722-5722

    • DOI

      10.1038/s41598-019-42114-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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

    • Related Report
      2018 Annual Research Report
    • 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

    • Related Report
      2018 Annual Research Report
    • 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

    • Related Report
      2017 Research-status Report
    • 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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The association of serum IFN-λ3 levels with liver fibrosis and hepatocarcinogenesis in chronic hepatitis C patients treated with direct-acting antiviral agents.2019

    • Author(s)
      Miyako Murakawa, Emi Inoue-Shinomiya, Yasuhiro Asahina, Mina Nakagawa, Jun Tsuchiya, Ayako Sato, Masato Miyoshi, Tomoyuki Tsunoda, Fukiko Kawai-Kitahata, Sayuri Nitta, Yasuhiro Itsui, Sei Kakinuma, Seishin Azuma, Mamoru Watanabe
    • Organizer
      The International Liver Congress 2019 (EASL)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] B型慢性肝炎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
    • Related Report
      2018 Annual Research Report
  • [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 (JDDW2018)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Genetic differences in hepatocellular carcinoma among chronic persistent hepatitis B virus infection with or without viral suppression and prior hepatitis B virus infection.2017

    • Author(s)
      Kawai-Kitahata F, Asahina Y, Kakinuma S, Murakawa M, Niita S, Nagata H, Kaneko S, Otani S, Miyoshi M, Tsunoda T, Sato A, Nakagawa M, Itsui Y, Azuma S, Tanaka S, Tanabe M, Maekawa S, Enomoto N, Watanabe M.
    • Organizer
      EASL The International Liver Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 潰瘍性大腸炎に合併した急性膵炎の2例2017

    • Author(s)
      保志ゆりか、矢内真人、松岡克善、日比谷秀爾、勝倉暢洋、竹中健人、鬼澤道夫、北畑富貴子、村川美也子、新田沙由梨、藤井俊光、岡田英理子、井津井康浩、中川美奈、柿沼 晴、東 正新、長堀正和、大塚和朗
    • Organizer
      日本消化器病学会関東支部第344回例会
    • Related Report
      2017 Research-status Report
  • [Presentation] 免疫抑制状態でのE 型肝炎慢性化症例の解析2017

    • Author(s)
      井津井康浩、大谷賢志、北畑富貴子、新田沙由梨、村川美也子、中川美奈、柿沼 晴、東 正新、高橋和明、朝比奈靖浩、渡辺 守
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] HCV-NS5A 阻害薬使用に関連する薬剤耐性変異ウイルスとその特徴2017

    • Author(s)
      新田沙由梨、村川美也子、永田紘子、佐藤綾子、三好正人、角田知之、浅野 侑、金子 俊、大谷賢志、北畑富貴子、東 正新、柿沼 晴、中川美奈、加藤孝宣、朝比奈靖浩、渡辺 守
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 食餌誘導性NASH モデルマウスにおけるMatrix Metalloporoteinase-2 の機能的解析2017

    • Author(s)
      柿沼 晴、浅野 侑、三好正人、佐藤綾子、角田知之、金子 俊、大谷賢志、永田紘子、北畑富貴子、村川美也子、新田沙由梨、井津井康浩、中川美奈、東 正新、朝比奈靖浩、渡辺 守
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 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、柿沼 晴、東 正新、井津井康浩、新田沙由梨、村川美也子、北畑富貴子、金子 俊、浅野 侑、井上恵美、角田知之、三好正人、佐藤綾子、渡辺 守
    • Organizer
      第16回日本肝がん分子標的治療研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS 細胞培養系を利用したHBV-HCV 共感染下でのHCV 排除により惹起されるHBV の再活性化メカニズムの解明2017

    • Author(s)
      金子 俊、柿沼 晴、朝比奈靖浩、紙谷聡英、三好正人、角田知之、四宮恵美、佐藤綾子、浅野 有、新田沙由梨、村川美也子、井津井靖浩、東 正新、渡辺 守
    • Organizer
      第24回肝細胞研究会
    • Related Report
      2017 Research-status Report
  • [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、田中信二、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
    • Related Report
      2017 Research-status Report
  • [Presentation] 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
      2017 Research-status Report
  • [Presentation] 2年間持続する貧血があり、イレウス症状を契機に診断に至った原発性小腸癌の1例2017

    • Author(s)
      近藤有紀、藤井 崇、日比谷秀爾、勝倉暢洋、竹中健人、鬼澤道夫、北畑富貴子、村川美也子、松岡克善、新田沙由梨、藤井俊光、岡田英理子、井津井康浩、齋藤詠子、中川美奈、柿沼 晴、長堀正和、大塚和朗、渡辺 守、高岡亜弓、山内慎一
    • Organizer
      日本消化器病学会関東支部第346回例会
    • Related Report
      2017 Research-status Report
  • [Presentation] B 型慢性肝疾患における核酸アナログ治療成績と肝発癌予測因子の検討2017

    • Author(s)
      村川美也子、朝比奈靖浩、中川美奈、東 正新、柿沼 晴、井津井康浩、新田沙由梨、北畑富貴子、金子俊、永田紘子、浅野 侑、三好正人、角田知之、井上恵美、佐藤綾子、渡辺 守
    • Organizer
      JDDW2017 第21回肝臓学会大会
    • Related Report
      2017 Research-status Report
  • [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, Nitta S, Kawai-Kitahata F, Nagata H, Kaneko S, Asano Y, Miyoshi M, Tsunoda T, Inoue-Shinomiya E, Sato A, Itsui Y, Kakinuma S, Azuma S, Watanabe M.
    • Organizer
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Research-status Report
    • 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
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] A 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
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Evaluation of an early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C patients treated with All-Oral DAAs - propensity score-matched analysis of a prospective database.2017

    • Author(s)
      Nakagawa M, Asahina Y, Nagata H, Kaneko S, Kawai-Kitahata F, Murakawa M, Nitta S, Itsui Y, Azuma S, Kakinuma S, Tanaka Y,Watanabe M.
    • Organizer
      AASLD The Liver Meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] B 型・C 型肝炎の抗ウイルス療法 最前線の治療エッセンス2017

    • Author(s)
      村川美也子、中川美奈、朝比奈靖浩.
    • Total Pages
      195
    • Publisher
      医薬ジャーナル社
    • ISBN
      9784753228430
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi