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Development of treatment for intractable portal vein thrombosis targeting intestinal flora-related coagulation disorders

Research Project

Project/Area Number 20K08280
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKanazawa University

Principal Investigator

Takatori Hajime  金沢大学, 附属病院, 准教授 (60613734)

Co-Investigator(Kenkyū-buntansha) 飯田 宗穂  金沢大学, 附属病院, 講師 (40705604)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords門脈血栓 / 肝硬変 / 腸内細菌叢 / 予後 / 再発因子 / 抗凝固療法 / 予後予測 / 門脈血栓症 / 凝固異常
Outline of Research at the Start

肝硬変における門脈血栓は予後悪化の原因になるが、抗凝固療法に難治性の門脈血栓につい てその原因は明らかになっていない。予備実験から肝硬変患者の腸内細菌叢異常により腸管 透過性亢進がもたらされることを我々は明らかにし、門脈に移行するLPSや細菌による“腸 内細菌叢関連凝固異常”が難治の原因の一つだと仮説を立てた。①門脈血栓患者に対する抗 凝固療法臨床試験において治療効果と腸内細菌叢関連因子の相関を解析、②門脈血栓患者便 細菌叢移植マウスにおける凝固異常のメカニズムの解明の2点を柱としてこの仮説を実証し、 門脈血栓難治例に対する治療法の開発のターゲットを見出す。

Outline of Final Research Achievements

We collected cases of portal vein thrombosis and found that patients with reduced antithrombotic activity had a poor prognosis, and in particular, that it was a factor related to death from liver failure. In addition, we published a paper in an overseas academic society that showed that in cases of partial splenic artery embolization (PSE) to lower portal vein pressure, which is attracting clinical attention as a salvage treatment for patients with portal hypertension, and in cases of difficulty in controlling anticoagulation treatment for the appearance of portal vein thrombi in splenectomy, symptoms of portal hypertension worsen, leading to increased gastrointestinal bleeding events and further affecting life prognosis. The results of treatment of patients with portal vein thrombosis treated with DOAC, the significant decrease in pre- and post-treatment FDP in successful cases, and the response rate in Yerdel classification 2/3 were presented at an overseas academic conference.

Academic Significance and Societal Importance of the Research Achievements

門脈血栓症例を集積し、抗凝固療法の有効性および再燃、臨床経過との関連を解析した。アンチトロンビン活性低下は有意に生命予後が不良であり、とくに肝不全死に関わる因子であることを解明し、英文論文として発表した。 また門脈圧亢進症例のサルベージ治療として臨床的に注目されている門脈圧低下目的での部分脾動脈塞栓術(PSE)や脾臓摘出術における門脈血栓の出現に対する抗凝固治療でのコントロール困難例においては門脈圧亢進症状が増悪し、消化管出血イベントの増加、さらに生命予後へ影響することを国内外の学会で発表し、論文化の予定である。

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

    (23 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Plasma Antithrombin III Levels Can Be a Prognostic Factor in Liver Cirrhosis Patients with Portal Vein Thrombosis2023

    • Author(s)
      Suda Tsuyoshi、Takatori Hajime、Hayashi Takehiro、Kaji Kiichiro、Nio Kouki、Terashima Takeshi、Shimakami Tetsuro、Arai Kuniaki、Yamashita Tatsuya、Mizukoshi Eishiro、Honda Masao、Okumura Kenichiro、Kozaka Kazuto、Yamashita Taro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 9 Pages: 7732-7732

    • DOI

      10.3390/ijms24097732

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of Thrombosis Volume, Anticoagulants, and Recurrence Factors in Portal Vein Thrombosis with Cirrhosis2020

    • Author(s)
      Suda Tsuyoshi、Takatori Hajime、Hayashi Takehiro、Horii Rika、Nio Kouki、Terashima Takeshi、Iida Noriho、Kitahara Masaaki、Shimakami Tetsuro、Arai Kuniaki、Yamashita Taro、Yamashita Tatsuya、Mizukoshi Eishiro、Honda Masao、Okumura Kenichiro、Kozaka Kazuto、Kaneko Shuichi
    • Journal Title

      Life

      Volume: 10 Issue: 9 Pages: 177-177

    • DOI

      10.3390/life10090177

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Management of biliary stricture in patients with IgG4-related sclerosing cholangitis2020

    • Author(s)
      Miyazawa Masaki、Takatori Hajime、Kawaguchi Kazunori、Kitamura Kazuya、Arai Kuniaki、Matsuda Koichiro、Urabe Takeshi、Inamura Katsuhisa、Komura Takuya、Mizuno Hideki、Fuchizaki Uichiro、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Mizukoshi Eishiro、Honda Masao、Kaneko Shuichi
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 4 Pages: e0232089-e0232089

    • DOI

      10.1371/journal.pone.0232089

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative analysis of liver functional reserve during lenvatinib and sorafenib for advanced hepatocellular carcinoma.2020

    • Author(s)
      Terashima T, Yamashita T, Takata N, Toyama T, Shimakami T, Takatori H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
    • Journal Title

      Hepatology Research

      Volume: - Issue: 7 Pages: 871-884

    • DOI

      10.1111/hepr.13505

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-28B variant as a predictor in patients with advanced hepatocellular carcinoma treated with hepatic arteiral infusion chemotherapy.2020

    • Author(s)
      Terashima T, Honda M, Toyama T, Shimakami T, Shimizu R, Takatori H, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: - Issue: 10 Pages: 1813-1820

    • DOI

      10.1111/jgh.15035

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inactivation of Transcriptional Repressor Capicua Confers Sorafenib Resistance in Human Hepatocellular Carcinoma2020

    • Author(s)
      Hashiba Tomomi、Yamashita Taro、et al
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 20 Issue: 2 Pages: 30039-4

    • DOI

      10.1016/j.jcmgh.2020.02.009

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脾摘およびPSEは難治性門亢症合併症の治療手段となりうる2023

    • Author(s)
      鷹取 元
    • Organizer
      第109回日本消化器病学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 主肺動脈径の拡張、肺動脈・大動脈の直径比の増加はPoPHのスクリーニングに有用である2023

    • Author(s)
      鷹取 元
    • Organizer
      第30回日本門脈圧亢進症学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] オキサリプラチンによる肝類洞閉塞症候群に対して集学的に治療した1例2023

    • Author(s)
      柳昌宏
    • Organizer
      第30回日本門脈圧亢進症学会総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Changes in endoscopic findings of portal hypertension due to splenectomy and partial splenic artery embolization2022

    • Author(s)
      宮澤正樹、鷹取 元
    • Organizer
      アジア太平洋肝臓学会オンコロジー2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 門脈血栓症に対するエドキサバン投与の安全性と有効性の前向き研究2022

    • Author(s)
      鷹取 元
    • Organizer
      日本消化器病学会週間2022
    • Related Report
      2022 Research-status Report
  • [Presentation] 門脈圧亢進症改善目的での脾摘・PSEの治療成績と問題点2022

    • Author(s)
      鷹取 元
    • Organizer
      第29回日本門脈圧亢進症学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 門脈血栓の体積と最大体積の相関,CT値と治療後再増悪に関わる検討2021

    • Author(s)
      須田 烈史,鷹取 元
    • Organizer
      第107回日本消化器病学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] アンチトロンビン活性低下は門脈血栓症の臨床経過予想に有用である2021

    • Author(s)
      鷹取 元
    • Organizer
      第57回日本肝臓学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 脾摘後門脈血栓症の臨床的特徴2021

    • Author(s)
      鷹取 元
    • Organizer
      第28回日本門脈圧亢進症学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 門脈血栓合併肝硬変症例におけるアンチトロンビン活性値による予後予測の試み2021

    • Author(s)
      梶喜一郎,鷹取 元
    • Organizer
      第29回日本消化器関連学会週間
    • Related Report
      2021 Research-status Report
  • [Presentation] 門脈血栓診療のポイント2021

    • Author(s)
      鷹取 元
    • Organizer
      第5回北陸門脈圧亢進症研究会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 門脈血栓治療の予後への影響とedoxaban投与の現状2020

    • Author(s)
      鷹取 元
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 門脈血栓治療とアンチトロンビン活性の肝硬変症例予後への影響2020

    • Author(s)
      鷹取 元
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 門脈血栓治療の最前線2020

    • Author(s)
      鷹取 元
    • Organizer
      第27回日本門脈圧亢進症学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 門脈血栓治療の予後への影響とedoxaban投与の現状2020

    • Author(s)
      鷹取 元
    • Organizer
      第27回日本門脈圧亢進症学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Investigation of Thrombosis Volume, Clinical Efficacy, Recurrence and Prognosis Factors in Portal Vein Thrombosis with Cirrhosis2020

    • Author(s)
      須田烈史、鷹取 元
    • Organizer
      JDDW2020
    • Related Report
      2020 Research-status Report
  • [Book] Portal Vein Thrombosis2021

    • Author(s)
      Hajime Takatori, Xingshun Qi
    • Total Pages
      171
    • Publisher
      Springer
    • ISBN
      9789813365384
    • Related Report
      2021 Research-status Report

URL: 

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

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