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Role of hepato-splenic interaction in portal hypertension

Research Project

Project/Area Number 20K08998
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionYamanashi Prefectural Hospital Organization

Principal Investigator

Iimuro Yuji  地方独立行政法人山梨県立病院機構山梨県立中央病院(がんセンター局ゲノム解析センター), ゲノム解析センター, 研究員 (30252018)

Co-Investigator(Kenkyū-buntansha) 弘津 陽介  地方独立行政法人山梨県立病院機構山梨県立中央病院(がんセンター局ゲノム解析センター), ゲノム解析センター, チーフ研究員 (10793838)
河野 寛  山梨大学, 大学院総合研究部, 特任准教授 (40322127)
鈴村 和大  兵庫医科大学, 医学部, 講師 (50434949)
波多野 悦朗  兵庫医科大学, 医学部, 非常勤講師 (80359801)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords門脈圧亢進症 / 脾線維化 / 肝細胞癌 / ゲノム解析 / 肝線維化 / 遺伝子解析 / 脾腫 / 肝発癌 / 脾摘
Outline of Research at the Start

肝炎治療の進歩に伴い、肝臓の線維化は改善するようになりました。一方、高度の肝硬変に合併する食道静脈瘤の発達や脾臓の腫大は、肝線維化が改善しても、遷延することがあります。我々は、こういった状況に脾臓が重要な働きをしている可能性について研究を行い、脾臓の線維化について報告しています。線維化などの脾臓における器質的変化が肝臓の線維化および肝発癌に及ぼす機序を解明し、社会貢献することを目的としています。

Outline of Final Research Achievements

The purpose of this study was to elucidate the relationship between splenomegaly/splenic fibrosis in a state of portal hypertension, and the development of liver fibrosis/hepatocellular carcinoma. In the liver tissues of patients with liver cirrhosis, the accumulation of anti-inflammatory macrophages around the attenuated fibrous tissue was observed after splenectomy. In order to investigate the relationship between the accumulated macrophages and the improvement of liver fibrosis, gene expression analysis at the cellular level was attempted, but no distinctive results have been obtained thus far. On the other hand, genomic analysis of hepatocellular carcinoma that developed in patients with liver cirrhosis accompanied by splenomegaly was conducted, comparing it with hepatocellular carcinoma in non-cirrhotic cases, to determine whether there are differences in the profile of mutated genes. However, no distinctive differences have been found up to the present.

Academic Significance and Societal Importance of the Research Achievements

ウイルス肝炎治療の進歩の一方で、残存する肝線維化に起因する肝発癌の抑制、門脈圧亢 進状態遷延による合併症の制御などが、重要な課題として浮上しています。これまでの検討で、腫大および線維化した脾臓が肝臓の線維化および肝発癌に関与する可能性が明らかになりつつあります。今回の研究で、脾臓摘出に伴う肝組織での細胞レベルの遺伝子発現、発症肝細胞癌での変異遺伝子の特徴などを行いましたが、まだ特徴的な変化は得られていません。今後、腫瘍内微小環境などの解析を加えて検討を行い、肝臓脾臓臓器相関の研究を行う予定です。

Report

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

    (9 results)

All 2023 2022 2021

All Presentation (9 results) (of which Int'l Joint Research: 5 results)

  • [Presentation] Significance of Tumor Genomic Differentiation (MC/IM) in the Treatment of Recurrent Hepatocellular Carcinoma.2023

    • Author(s)
      Iimuro Y, Takano A, Amemiya K, Hirotsu Y, Mochizuki H, Obi S, Omata M.
    • Organizer
      APASL2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multifocal HCCs genetically classified as Multicentric Occurrence (MO) possess better prognosis after surgery comparing to Intrahepatic Metastasis (IM).2022

    • Author(s)
      Iimuro Y, Takano A, Amemiya K, Hirotsu Y, Mochizuki H, Obi S, Omata M.
    • Organizer
      APASL 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genomic profile of hepatocellular carcinoma after sustained virologic response.2022

    • Author(s)
      Ohyama H, Obi S, Ooka Y, Hirotsu Y, Amemiya K, Iimuro Y, Mochizuki H, Kato N, Omata M.
    • Organizer
      APASL 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Major signaling pathways in 195 HCC samples including multiple occurrence.2022

    • Author(s)
      Amemiya K, Hirotsu Y, Obi S, Iimuro Y, Omata M.
    • Organizer
      APASL 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of genetic differentiation between MC and IM in multinodular HCCs.2022

    • Author(s)
      Iimuro Y
    • Organizer
      APASL Oncology 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Post-SVR時代の肝癌治療におけるMinimal Invasive Hepatectomyの有用性2021

    • Author(s)
      飯室勇二、小尾俊太郎、望月仁、大山宏、弘津陽介、雨宮健司、小俣政男
    • Organizer
      第57回日本肝癌研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] Genetic discrimination between Multicentric Occurrence and Intrahepatic Metastasis in multifocal HCC2021

    • Author(s)
      Yuji Iimuro, Atsushi Takano, Kenji Amemiya, Yosuke Hirotsu, Hitoshi Mochizuki, Shuntaro Obi, and Masao Omata
    • Organizer
      APASL Oncology 2021
    • Related Report
      2021 Research-status Report
  • [Presentation] Minimal Invasive Hepatectomy in the Post-SVR Era2021

    • Author(s)
      Yuji Iimuro, Atsushi Takano, Shuntaro Obi, Hitoshi Mochizuki, Masao Omata
    • Organizer
      APASL Oncology 2021
    • Related Report
      2021 Research-status Report
  • [Presentation] Multifocal HCCs genetically classified as Multicentric Occurrence (MO) possess better prognosis after surgery comparing to Intrahepatic Metastasis (IM)2021

    • Author(s)
      Yuji Iimuro1, Atsushi Takano, Kenji Amemiya, Yosuke Hirotsu, Hitoshi Mochizuki, Shuntaro Obi, and Masao Omata
    • Organizer
      APASL 2022
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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