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MicroRNA as a biomarker for prediction of HCC development after achieving an SVR

Research Project

Project/Area Number 16K09369
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

Enomoto Masaru  大阪市立大学, 大学院医学研究科, 准教授 (20423874)

Co-Investigator(Kenkyū-buntansha) 村上 善基  大阪市立大学, 大学院医学研究科, 准教授 (00397556)
河田 則文  大阪市立大学, 大学院医学研究科, 教授 (30271191)
田守 昭博  大阪市立大学, 大学院医学研究科, 准教授 (30291595)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsC型肝炎 / マイクロRNA / SVR / 線維化 / バイオマーカー / 内科 / 肝炎
Outline of Final Research Achievements

Direct-acting antivirals (DAAs) can result in a sustained virologic response (SVR) in >90% of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate histological improvement after obtaining an SVR to DAAs in patients with HCV. Among 691 patients with chronic hepatitis C who had an SVR to DAAs, 51 underwent liver biopsy 41±20 weeks after the end of therapy. In 20 patients, liver biopsies obtained a median of 1.2 years before the start of treatment were available. Among the 51 patients who underwent post-SVR biopsies, the grade of inflammation was A0 in 18, A1 in 24, A2 in 8, and A3 in 1; the stage of fibrosis was F0 in 3, F1 in 20, F2 in 15, F3 in 9, and F4 in 4. In the 20 paired biopsies, the inflammation grade regressed (p = 0.0043), but the fibrosis stage did not (p = 0.45). Even if ALT become normal after having an SVR, significant histological inflammation was found in some patients. The improvement in liver fibrosis was not evident in the short term

Academic Significance and Societal Importance of the Research Achievements

我が国には500万人以上の慢性肝疾患患者が存在するが、その数は非アルコール性脂肪肝炎の増加に伴い増え続けている。また慢性肝疾患の終末像である肝硬変からは、例え肝炎ウイルスが制御されたとしても年率3~7%の割合で肝発がんが起こると考えられている。肝発がんは肝の壊死・炎症と線維化に密接に関係しており、肝線維化に関連するバイオマーカーの探索から肝発がんの機構を明らかにし、発がん高リスク患者を囲い込もうとする本研究の学術的意義は非常に高い。慢性肝疾患の制御は公衆衛生上も大変重要な国民的健康問題であり、臨床的にこれに利用可能なバイオマーカーを開発することが出来れば社会的に貢献できる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 14 results,  Peer Reviewed: 14 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] Remission of Psoriasis After Treatment of Chronic Hepatitis C Virus Infection With Direct-Acting Antivirals2018

    • Author(s)
      Enomoto Masaru、Tateishi Chiharu、Tsuruta Daisuke、Tamori Akihiro、Kawada Norifumi
    • Journal Title

      Annals of Internal Medicine

      Volume: 168 Issue: 9 Pages: 678-678

    • DOI

      10.7326/l17-0613

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Stagnation of histopathological improvement is a predictor of hepatocellular carcinoma development after hepatitis C virus eradication2018

    • Author(s)
      Motoyama H, Tamori A, Kubo S, Uchida-Kobayashi S, Takemura S, Tanaka S, Ohfuji S, Teranishi Y, Kozuka R, Kawamura E, Hagihara A, Morikawa H, Enomoto M, Murakami Y, Kawada N.
    • Journal Title

      PLoS One.

      Volume: 13 Issue: 3 Pages: e0194163

    • DOI

      10.1371/journal.pone.0194163

    • NAID

      120006411697

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020442

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Short-term histological evaluations after achieving a sustained virologic response to direct-acting antiviral treatment for chronic hepatitis C2018

    • Author(s)
      Enomoto Masaru、Ikura Yoshihiro、Tamori Akihiro、Kozuka Ritsuzo、Motoyama Hiroyuki、Kawamura Etsushi、Hagihara Atsushi、Fujii Hideki、Uchida-Kobayashi Sawako、Morikawa Hiroyasu、Murakami Yoshiki、Kawada Norifumi
    • Journal Title

      United European Gastroenterology Journal

      Volume: 6 Issue: 9 Pages: 1391-1400

    • DOI

      10.1177/2050640618791053

    • NAID

      120006533846

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020542

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor-na?ve patients with chronic HCV genotype 1b infection in a real-world cohort2018

    • Author(s)
      Kozuka R.、Hai H.、Motoyama H.、Hagihara A.、Fujii H.、Uchida-Kobayashi S.、Morikawa H.、Enomoto M.、Murakami Y.、Kawada N.、Tamori A.
    • Journal Title

      Journal of Viral Hepatitis

      Volume: - Issue: 5 Pages: 535-542

    • DOI

      10.1111/jvh.12850

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Successful direct-acting antiviral treatment of three patients with genotype 2/1 recombinant hepatitis C virus2018

    • Author(s)
      Okada Masako、Hai Hoang、Tamori Akihiro、Uchida-Kobayashi Sawako、Enomoto Masaru、Kumada Hiromitsu、Kawada Norifumi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 12 Issue: 3 Pages: 213-217

    • DOI

      10.1007/s12328-018-0922-9

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2019774

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy2017

    • Author(s)
      Tamori A.、Abiru S.、Enomoto H.、Kioka K.、Korenaga M.、Tani J.、Enomoto M.、Sugiyama M.、Masaki T.、Kawada N.、Yatsuhashi H.、Nishiguchi S.、Mizokami M.
    • Journal Title

      Journal of Viral Hepatitis

      Volume: - Issue: 5 Pages: 608-611

    • DOI

      10.1111/jvh.12840

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with chronic hepatitis C-related hepatocellular carcinoma2017

    • Author(s)
      Hai Hoang、Tamori Akihiro、Thuy Le Thi Thanh、Yoshida Kanako、Hagihara Atsushi、Kawamura Etsushi、Uchida-Kobayashi Sawako、Morikawa Hiroyasu、Enomoto Masaru、Murakami Yoshiki、Kawada Norifumi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11912

    • DOI

      10.1038/s41598-017-10363-5

    • NAID

      120006346630

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2020474

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Outcomes for Cirrhotic Patients with Hepatitis C Virus 1b Treated with Asunaprevir and Daclatasvir Combination2017

    • Author(s)
      Tamori Akihiro、Hai Hoang、Uchida-Kobayashi Sawako、Enomoto Masaru、Kozuka Ritsuzo、Motoyama Hiroyuki、Kawamura Etsushi、Hagihara Atsushi、Teranishi Yuga、Yoshida Kanako、Morikawa Hiroyasu、Murakami Yoshiki、Kawada Norifumi
    • Journal Title

      Annals of Hepatology

      Volume: 16 Issue: 5 Pages: 734-741

    • DOI

      10.5604/01.3001.0010.2732

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of HCV RNA in Sustained Virologic Response to?Direct-Acting Antiviral Agents: Occult or Science Fiction?2017

    • Author(s)
      Enomoto Masaru、Murakami Yoshiki、Kawada Norifumi
    • Journal Title

      Gastroenterology

      Volume: 153 Issue: 1 Pages: 327-328

    • DOI

      10.1053/j.gastro.2017.03.075

    • Related Report
      2017 Research-status Report
  • [Journal Article] Long-Term Follow-Up of Resistance-Associated Substitutions in Hepatitis C Virus in Patients in Which Direct Acting Antiviral-Based Therapy Failed2017

    • Author(s)
      Yoshida Kanako、Hai Hoang、Tamori Akihiro、Teranishi Yuga、Kozuka Ritsuzo、Motoyama Hiroyuki、Kawamura Etsushi、Hagihara Atsushi、Uchida-Kobayashi Sawako、Morikawa Hiroyasu、Enomoto Masaru、Murakami Yoshiki、Kawada Norifumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18 Issue: 5 Pages: 962-962

    • DOI

      10.3390/ijms18050962

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Detection of HCV RNA in Sustained Virologic Response to Direct-Acting Antiviral Agents: Occult or Science Fiction?2017

    • Author(s)
      Enomoto M, Murakami Y, Kawada N.
    • Journal Title

      Gastroenterology

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Correlation between polymorphism in the inosine triphosphatase and the reductions in hemoglobin concentration and ribavirin dose during sofosbuvir and ribavirin therapy2016

    • Author(s)
      Tamori A, Yoshida K, Kurai O, Kioka K, Hai H, Kozuka R, Motoyama H, Kawamura E, Hagihara A, Uchida-Kobayashi S, Morikawa H, Enomoto M, Murakami Y, Kawada N
    • Journal Title

      Hepatol Res.

      Volume: 32 Issue: 8 Pages: 1495-1502

    • DOI

      10.1111/jgh.13743

    • NAID

      120006510936

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2019975

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Putting "sticky notes" on the electronic medical record to promote intra-hospital referral of hepatitis B and C virus-positive patients to hepatology specialists: an exploratory study.2016

    • Author(s)
      Fujii H, Yamaguchi S, Kurai O, Miyano M, Ueda W, Oba H, Aoki T, Enomoto M, Kawada N, Okawa K.
    • Journal Title

      BMC Infect Dis.

      Volume: 16 Issue: 1 Pages: 410-410

    • DOI

      10.1186/s12879-016-1765-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent advances in antiviral therapy for chronic hepatitis C2016

    • Author(s)
      Tamori A, Enomoto M, Kawada N.
    • Journal Title

      Mediators of Inflammation

      Volume: 2016 Pages: 1-11

    • DOI

      10.1155/2016/6841628

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b2016

    • Author(s)
      Tamori A, Yoshida K, Kurai O, Kioka K, Hai H, Kozuka R, Motoyama H, Kawamura E, Hagihara A, Uchida-Kobayashi S, Morikawa H, Enomoto M, Murakami Y, Kawada N.
    • Journal Title

      Hepatol Res

      Volume: 46 Issue: 13 Pages: 1311-1320

    • DOI

      10.1111/hepr.12689

    • NAID

      120006534926

    • URL

      https://ocu-omu.repo.nii.ac.jp/records/2019875

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Establishing efficient systems to promote intra-hospital referrals of hepatitis virus carriers to hepatology specialists2018

    • Author(s)
      M Enomoto, S Uchida, N Kawada
    • Organizer
      JDDW2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 麻酔科医に必要なB型・C型肝炎の知識2018

    • Author(s)
      榎本大
    • Organizer
      日本臨床麻酔学会 第38回大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Establishing Efficient Systems through Electronic Medical Records to Promote Intra-Hospital Referrals of Hepatitis Virus Carriers to Hepatology Specialists: A Multicenter Questionnaire Survey of 1,314 Healthcare2018

    • Author(s)
      Masaru Enomoto, Syuuichi Sato, Atsushi Suetsugu, Tomomitsu Matono, Isao Hidaka, Minoru Sakamoto, Mika Horino, Kiyoaki Ito, Koji Ogawa, Jun Inoue, Masaaki Korenaga
    • Organizer
      69th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] “Normal” ALT by central laboratory criteria but >30 U/L for males and >19 U/L for females is predictive of residual inflammation in liver biopsies after sustained virologic response to direct-acting antivirals for chronic hepatitis C2018

    • Author(s)
      Masaru Enomoto, Yoshihiro Ikura, Akihiro Tamori, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Hideki Fujii, Sawako Uchida-Kobayashi, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada
    • Organizer
      69th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Changes in clinical and histological parameters predictive of liver fibrosis and/or HCC development after direct-acting antiviral treatment for chronic hepatitis C2017

    • Author(s)
      M Enomoto, A Tamori, R Kozuka, H Motoyama, A Hagihara, H Fujii, S Uchida-Kobayashi, H Morikawa, Y Murakami, N Kawada
    • Organizer
      Asian Pacific Association for the Study of the Liver (APASL) Single Topic Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型慢性肝疾患に対するDAA治療前後の短期的肝線維化改善効果について2017

    • Author(s)
      榎本大、田守昭博、河田則文
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] C型慢性肝疾患に対するDAA治療前後の肝病理組織所見の変化について2017

    • Author(s)
      榎本大、伊倉義弘 、元山宏行 、小塚立蔵 、萩原淳司、藤井英樹、打田佐和子、森川浩安、村上善基、田守昭博、河田則文
    • Organizer
      第24回日本門脈圧亢進症学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] DAA治療による肝線維化改善効果:非侵襲的評価、病理学的検討を含めて2017

    • Author(s)
      榎本大、村上善基、河田則文
    • Organizer
      第21回日本肝臓学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Short-term histological evaluations after achieving a sustained virological response to direct-acting antiviral treatment for chronic hepatitis C2017

    • Author(s)
      Masaru Enomoto, Akihiro Tamori, Ritsuzo Kozuka, Hiroyuki Motoyama, Atsushi Hagihara, Hideki Fujii, Sawako Uchida-Kobayashi, Hiroyasu Morikawa, Yoshiki Murakami, Yoshihiro Ikura, Norifumi Kawada
    • Organizer
      68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院および関連施設におけるC型肝炎ウイルス感染者の拾い上げに向けた取り組み2016

    • Author(s)
      榎本大、森川浩安、河田則文
    • 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
    • Related Report
      2016 Research-status Report
  • [Presentation] Promotion of intra-hospital referral of hepatitis B and C virus carriers to hepatology specialists by electronic medical record-based alert system: a case study at a university hospital2016

    • Author(s)
      M. Enomoto, S. Uchida-Kobayashi, H. Fujii, A. Iida-Ueno, H. Motoyama, R. Kozuka, A. Hagihara, E. Kawamura, H. Morikawa, Y. Murakami, A. Tamori, N. Kawada
    • Organizer
      24th United European Gastroenterology Week (UEGW)
    • Place of Presentation
      ウイーン(オーストリア)
    • Year and Date
      2016-10-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] C型慢性肝疾患に対するIFNフリーDAA治療前後の門脈圧に関連する検査値の変化について2016

    • Author(s)
      榎本大、田守昭博、寺西優雅、元山宏行、小塚立蔵、川村悦史、萩原淳司、打田佐和子、森川浩安、村上善基、河田則文
    • Organizer
      第23回日本門脈圧亢進症学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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