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Clinical study to develop the novel therapy for decompensated liver cirrhosis combinede with interventional radiology and liver regeneration

Research Project

Project/Area Number 20K08137
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionYamaguchi University

Principal Investigator

Ishikawa Tsuyoshi  山口大学, 大学院医学系研究科, 准教授 (20569305)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords非代償性肝硬変 / IVR治療 / 肝再生 / 再生療法
Outline of Research at the Start

我々が開発した「非代償性肝硬変症に対する自己骨髄細胞投与療法」を基盤とし、その治療効率を高めるべく種々の改良を重ねて基礎・臨床研究を進めてきた。
研究代表者は、大学院在籍中~米国留学中に幹細胞由来肝再生および細胞外基質制御機構に関する基礎研究に従事し、また帰学後の臨床研究において門脈圧亢進症に対するIVR治療が非代償性肝硬変患者にもたらす様々な有効性について報告してきた。
本研究では「バルーン閉塞下逆行性経静脈的塞栓術」の多種多様な効果に着目し、IVR治療と再生療法の融合による、肝再生促進・肝線維化抑制さらには生命予後延長を目指した、低侵襲かつ効率的な非代償性肝硬変に対する新規治療戦略を確立する。

Outline of Final Research Achievements

Development of portosystemic shunts has been reported to be one of prognostic factors in patients with liver cirrhosis with portal hypertension. The aim of this clinical research is to elucidate the impact of portosystemic shunt occlusion on hepatic fibrosis and cross-talk between liver and lung. The present study demonstrated that balloon-occluded retrograde transvenous obliteration could result in increased portal venous flow and elevated nitrogen oxide levels, leading to an improvement in hepatic fibrosis. In addition, from the results of this study, the procedure might be a therapeutic option for portopulmonary hypertension through the correction of pulmonary hemodynamics related to the regulation of both systemic hemodynamics and humoral substances by portosystemic shunt occlusion.

Academic Significance and Societal Importance of the Research Achievements

門脈-大循環シャント(PSS)は、肝臓を介することなく門脈血流を大循環に流出させる異常血管であり、肝循環のみならず全身循環にも影響を及ぼし得る。従ってバルーン閉塞下逆行性経静脈的塞栓術(BRTO)によるPSS閉塞は、肝機能や肝線維化の改善のみならず、全身循環障害の是正による他臓器の機能改善をもたらすことが予想される。PSS合併症例においてBRTOが肝線維化および肝肺連関に及ぼす影響に関する報告は未だなく、その未知なる付随効果を証明することで非代償性肝硬変患者の予後延長につながる新規治療戦略の構築が期待できる。従って、本研究の学術的意義ならびに社会的意義は大きいものと自己評価する。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 2020

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (20 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Portopulmonary Hypertension Treated by Occlusion of a Spontaneous Portosystemic Shunt Followed by Endothelin Receptor Antagonist Administration2024

    • Author(s)
      Ishikawa Tsuyoshi、Kawamoto Daiki、Nishimura Tatsuro、Suetomi Takeshi、Kobayashi Shigeki、Takami Taro
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: 35 Issue: 2 Pages: 313-315

    • DOI

      10.1016/j.jvir.2023.10.028

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drastic Improvement in Hepatitis B/C Virus-induced Decompensated Liver Cirrhosis Treated by Total Management Consisting of Interventional Radiology, Endoscopy, and Pharmacotherapy2022

    • Author(s)
      Nishimura Tatsuro、Ishikawa Tsuyoshi、Kawamoto Daiki、Sasaki Ryo、Matsuda Takashi、Takami Taro
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 21 Pages: 3217-3223

    • DOI

      10.2169/internalmedicine.9240-21

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-11-01
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A combination of liver stiffness and international normalized ratio is an ideal prognostic predictor of portosystemic shunt occlusion in patients with portal hypertension2022

    • Author(s)
      Ishikawa Tsuyoshi、Egusa Maho、Fujioka Tsuyoshi、Nishiyama Natsuko、Kawamoto Daiki、Sasaki Ryo、Nishimura Tatsuro、Tanabe Norikazu、Oono Takashi、Saeki Issei、Takami Taro
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 3 Pages: 246-256

    • DOI

      10.1007/s00535-022-01947-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification2021

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Matsuda Takashi、Iwamoto Takuya、Saeki Issei、Hidaka Isao、Takami Taro、Sakaida Isao
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 9 Pages: 1331-1342

    • DOI

      10.2169/internalmedicine.6267-20

    • NAID

      130008033267

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-05-01
    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful Management With Dual Therapy of Lenvatinib and Macitentan for HCC With Portopulmonary Hypertension2021

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Matsuda Takashi、Saeki Issei、Takami Taro、Wada Yasuaki、Yano Masafumi、Sakaida Isao
    • Journal Title

      Hepatology

      Volume: 74 Issue: 4 Pages: 2300-2303

    • DOI

      10.1002/hep.31865

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism2021

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Matsuda Takashi、Iwamoto Takuya、Saeki Issei、Hidaka Isao、Takami Taro、Sakaida Isao
    • Journal Title

      Journal of Gastroenterology

      Volume: 56 Issue: 4 Pages: 382-394

    • DOI

      10.1007/s00535-021-01762-7

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rendezvous therapy with endoscopic and endovascular treatments for rectal arteriovenous malformation: A case report2021

    • Author(s)
      Matsuda Takashi、Ishikawa Tsuyoshi、Oono Takashi、Sasaki Ryo、Hidaka Isao、Okada Munemasa、Sakaida Isao
    • Journal Title

      Endoscopy

      Volume: - Issue: 03 Pages: E77-E78

    • DOI

      10.1055/a-1388-6021

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significant improvement in portal‐systemic liver failure symptoms and successful management of portal‐splenic venous hemodynamics by the combination of interventional radiology and pharmacotherapy2020

    • Author(s)
      Ishikawa Tsuyoshi、Hamamoto Kaori、Sasaki Ryo、Nishimura Tatsuro、Matsuda Takashi、Iwamoto Takuya、Takami Taro、Sakaida Isao
    • Journal Title

      Hepatology Research

      Volume: 50 Issue: 10 Pages: 1201-1208

    • DOI

      10.1111/hepr.13545

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 門脈-大循環シャント閉塞が肺動脈循環・全身循環および液性因子に及ぼす影響~BRTOはPoPHに有効か?~2023

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第109回日本消化器病学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Efficacy of BRTO on Portopulmonary Hypertension-from a perspective of hemodynamics and humoral substances-2023

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第52回日本IVR学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Spontaneous portosystemic shunts as a therapeutic target for portopulmonary hypertension2023

    • Author(s)
      Tsuyoshi Ishikawa, Natsuko Nishiyama, Maho Egusa, Tsuyoshi Fujioka, Daiki Kawamoto, Ryo Sasaki, Tatsuro Nishimura, Norikazu Tanabe, Issei Saeki, and Taro Takami
    • Organizer
      The Liver Meeting 2023, AASLD
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 門脈肺高血圧症診断における胸部CT検査の臨床的有用性2022

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第108回日本消化器病学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 門脈-大循環シャント合併慢性肝不全に対するBRTOの適応と意義~予後予測因子の再検証~2022

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第58回 日本肝臓学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Portosystemic shunt syndromeの予後延長を目指した治療戦略~Point of No Returnの探求~2022

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第29回 日本門脈圧亢進症学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] A Case of Cardiofundal Varices (CFV)2022

    • Author(s)
      Tsuyoshi Ishikawa
    • Organizer
      The International Liver Congress 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Liver stiffness and international normalized ratio may predict prognosis following portosystemic shunt occlusion in patients with portal hypertension2022

    • Author(s)
      Tsuyoshi Ishikawa, Maho Egusa, Tsuyoshi Fujioka, Daiki Kawamoto, Tatsuro Nishimura, Ryo Sasaki, and Taro Takami
    • Organizer
      The Liver Meeting 2022, AASLD
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 難治性脳症に対する バルーン閉塞下逆行性経静脈的塞栓術2022

    • Author(s)
      石川 剛、高見太郎
    • Organizer
      第58回日本腹部救急医学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 「HVPG低下」の観点からPSEの臨床的有用性を再考する2021

    • Author(s)
      石川 剛、高見太郎、坂井田 功
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] BRTOが全身循環に及ぼす影響~肝心相関へのアプローチ~2021

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第28回日本門脈圧亢進症学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 胸部CT検査は門脈肺高血圧症の拾い上げに有用か?2021

    • Author(s)
      石川 剛、西村達朗、高見太郎
    • Organizer
      第44回日本肝臓学会西部会
    • Related Report
      2021 Research-status Report
  • [Presentation] 門脈系血行動態の改変による肝線維化改善の可能性 ~IVRによる類洞周囲微小環境の変化~2021

    • Author(s)
      石川 剛、高見太郎
    • Organizer
      第35回肝類洞壁細胞研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] BRTO症例における門脈-脾静脈系血行動態把握の意義2020

    • Author(s)
      石川 剛、高見太郎、坂井田 功
    • Organizer
      第43回日本肝臓学会東部会
    • Related Report
      2020 Research-status Report
  • [Presentation] 「HVPG response」の観点から見た部分的脾動脈塞栓術の有用性2020

    • Author(s)
      石川 剛、高見太郎、坂井田 功
    • Organizer
      JDDW2020
    • Related Report
      2020 Research-status Report
  • [Presentation] BRTOの有効性・安全性の向上を目指した治療戦略2020

    • Author(s)
      石川 剛、坂井田 功
    • Organizer
      第23回BRTO研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] シャント性脳症に対するBRTO~胃静脈瘤に対するBRTOとの比較~2020

    • Author(s)
      石川 剛、佐々木 嶺、松田崇史、坂井田 功
    • Organizer
      第22回肝不全治療研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] HVPGを用いてPSEによる門脈圧降下作用を再考する2020

    • Author(s)
      石川 剛、佐々木 嶺、松田崇史、坂井田 功
    • Organizer
      第27回日本門脈圧亢進症学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 非代償性肝硬変に対する部分的脾動脈塞栓術は是か非か~有効性と安全性の観点より~2020

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] BRTO後の予後予測因子に関する統計解析2020

    • Author(s)
      石川 剛、高見太郎、坂井田 功
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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