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Exploring Pathology of Non-Alcoholic Fatty Liver Disease Based on Etiology Using Digital Pathology

Research Project

Project/Area Number 21K07916
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYAAKI hisamitsu  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (20437891)

Co-Investigator(Kenkyū-buntansha) 福島 真典  長崎大学, 病院(医学系), 助教 (80835596)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsデジタルパソジー / 線維化 / 人工知能 / デジタルパソロジー / AI / MASH / 線維シグネチャー / NASH / NAFLD / 線維化パターン / 非アルコール性脂肪性肝疾患 / 脂肪化
Outline of Research at the Start

非アルコール性脂肪性肝疾患(NAFLD)は遺伝子、メタボリックシンドローム、環境因子が相互に関連し発症するヘテロな病態である。従来の病理医による人の目の診断では、その原因因子の判別は困難であった。近年、病理標本をデジタル化し、およそ400の病理像のパラメーターの網羅的な定量解析が可能となった。従来の病理医の評価に比較し、膨大なデータの客観的で質的な評価が可能となり、新しい知見が得られるようになってきている。本研究はデジタルパソロジーの技術を用いてNAFLD患者の病理パターンの網羅的解析を行い 、NAFLDを原因に基づいて新たに分類し、そのバイオマーカーを見出すことを目的とする。

Outline of Final Research Achievements

This study is a comprehensive analysis of pathological patterns in MASH patients using digital pathology techniques. Study 1 found significant differences in fibrosis patterns between hepatocellular carcinoma and nonhepatocellular carcinoma groups in liver transplant recipients with NASH cirrhosis in terms of morphological changes of fibers. The same approach was used to compare fibrosis patterns in NASH liver biopsy cases. Similarly, significant differences were found in morphology scores. The overall score was able to predict carcinogenesis with high accuracy. Study 2 also found differences in ALD and NASH cirrhosis. The fibrosis pattern was similar to ALD in the MetALD group, but some NASH-like features were observed.

Academic Significance and Societal Importance of the Research Achievements

NASH由来肝癌のHCCの発生はウイルス肝炎由来の発癌と比較すると比較すると低く、絞り込みが難しい。今回我々が見出した病理学的因子によりMASH発癌を高精度で予測できる可能がある。またALD肝硬変とMASH肝硬変の病理学的違いは従来判別不能であったが今回線維パターンのにより判別可能となった。今回見出した形態学的変化が生じるメカニズムを解明すれば、ALDやMASHの新たなる対策が判明する可能性がある。

Report

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

    (23 results)

All 2024 2023 2022 2021

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Recent Advances in Endoscopic Ultrasound for Gallbladder Disease Diagnosis2024

    • Author(s)
      Takahashi Kosuke、Ozawa Eisuke、Shimakura Akane、Mori Tomotaka、Miyaaki Hisamitsu、Nakao Kazuhiko
    • Journal Title

      Diagnostics

      Volume: 14 Issue: 4 Pages: 374-374

    • DOI

      10.3390/diagnostics14040374

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of deep learning model for predicting immune checkpoint inhibitor treatment efficacy on contrast-enhanced computed tomography images of hepatocellular carcinoma2024

    • Author(s)
      Nakao Yasuhiko、Nishihara Takahito、Sasaki Ryu、Fukushima Masanori、Miuma Satoshi、Miyaaki Hisamitsu、Akazawa Yuko、Nakao Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 6576-6576

    • DOI

      10.1038/s41598-024-57078-y

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Most Cases of Cryptogenic Cirrhosis May Be Nonobese Nonalcoholic Steatohepatitis - Risk Factors of Liver Steatosis After Liver Transplantation for Cryptogenic Cirrhosis: A Retrospective Study2023

    • Author(s)
      Fukushima Masanori、Miyaaki Hisamitsu、Sasaki Ryu、Haraguchi Masafumi、Miuma Satoshi、Hara Takanobu、Soyama Akihiko、Hidaka Masaaki、Eguchi Susumu、Nakao Kazuhiko
    • Journal Title

      Internal Medicine

      Volume: 62 Issue: 10 Pages: 1415-1423

    • DOI

      10.2169/internalmedicine.0514-22

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2023-05-15
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of the novel Franseen needle versus the fine‐needle aspiration needle in endoscopic ultrasound‐guided tissue acquisition for cancer gene panel testing: A propensity score‐matching analysis2023

    • Author(s)
      Mori Tomotaka、Ozawa Eisuke、Shimakura Akane、Takahashi Kosuke、Matsuo Satoshi、Tajima Kazuaki、Nakao Yasuhiko、Fukushima Masanori、Sasaki Ryu、Miuma Satoshi、Miyaaki Hisamitsu、Okano Shinji、Nakao Kazuhiko
    • Journal Title

      JGH Open

      Volume: 7 Issue: 9 Pages: 652-658

    • DOI

      10.1002/jgh3.12965

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoglycemia measured by flash glucose monitoring system predicts liver-related events in chronic liver disease patients2023

    • Author(s)
      Sasaki Ryu、Taura Naota、Nakao Yasuhiko、Fukushima Masanori、Haraguchi Masafumi、Miuma Satoshi、Miyaaki Hisamitsu、Nakao Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 13791-13791

    • DOI

      10.1038/s41598-023-40910-2

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial2023

    • Author(s)
      Sawase Hironori、Ozawa Eisuke、Yano Hiroshi、Ichinomiya Taiga、Yano Rintaro、Miyaaki Hisamitsu、Komatsu Naohiro、Ayuse Takao、Kurata Shinji、Sato Shuntaro、Pinkham Maximilian Ichabod、Tatkov Stanislav、Ashizawa Kazuto、Nagata Kazuyoshi、Nakao Kazuhiko
    • Journal Title

      BMC Anesthesiology

      Volume: 23 Issue: 1

    • DOI

      10.1186/s12871-023-02125-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regular protocol liver biopsy is useful to adjust immunosuppressant dose after adult liver transplantation2022

    • Author(s)
      Narita Shohei、Miuma Satoshi、Okudaira Sadayuki、Koga Yoshito、Fukushima Masanori、Sasaki Ryu、Haraguchi Masafumi、Soyama Akihiko、Hidaka Masaaki、Miyaaki Hisamitsu、Futakuchi Mitsuru、Nagai Kazuhiro、Ichikawa Tatsuki、Eguchi Susumu、Nakao Kazuhiko
    • Journal Title

      Clinical Transplantation

      Volume: 37 Issue: 3

    • DOI

      10.1111/ctr.14873

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Automated fibrosis phenotyping of liver tissue from non-tumor lesions of patients with and without hepatocellular carcinoma after liver transplantation for non-alcoholic fatty liver disease2022

    • Author(s)
      Nakamura Yutaka、Miyaaki Hisamitsu、Miuma Satoshi、Akazawa Yuko、Fukusima Masanori、Sasaki Ryu、Haraguchi Masafumi、Soyama Akihiko、Hidaka Masaaki、Eguchi Susumu、Nakao Kazuhiko
    • Journal Title

      Hepatology International

      Volume: 16 Issue: 3 Pages: 555-561

    • DOI

      10.1007/s12072-022-10340-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluating the Role of Hepatobiliary Phase of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Predicting Treatment Impact of Lenvatinib and Atezolizumab plus Bevacizumab on Unresectable Hepatocellular Carcinoma2022

    • Author(s)
      Sasaki Ryu、Nagata Kazuyoshi、Fukushima Masanori、Haraguchi Masafumi、Miuma Satoshi、Miyaaki Hisamitsu、Soyama Akihiko、Hidaka Masaaki、Eguchi Susumu、Shigeno Masaya、Yamashima Mio、Yamamichi Shinobu、Ichikawa Tatsuki、Kugiyama Yuki、Yatsuhashi Hiroshi、Nakao Kazuhiko
    • Journal Title

      Cancers

      Volume: 14 Issue: 3 Pages: 827-827

    • DOI

      10.3390/cancers14030827

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proposal for new sleep disorder criteria in patients with chronic liver disease: Influence of liver‐related complications2021

    • Author(s)
      Miyaaki Hisamitsu、Hiraoka Atsuhi、Haraguchi Masafumi、Uojima Haruki、Kawaratani Hideto、Hiramatsu Akira、Hanai Tatsunori、Hiasa Yoichi、Yoshiji Hitoshi、Okita Kiwamu、Nakao Kazuhiko、Koike Kazuhiko
    • Journal Title

      Hepatology Research

      Volume: 52 Issue: 4 Pages: 364-370

    • DOI

      10.1111/hepr.13731

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The impact of single-nucleotide polymorphisms on liver stiffness and controlled attenuation parameter in patients treated with direct-acting antiviral drugs for hepatitis C infection2021

    • Author(s)
      Matsumoto Kosuke、Miyaaki Hisamitsu、Fukushima Masanori、Sasaki Ryu、Haraguchi Masafumi、Miuma Satoshi、Nakao Kazuhiko
    • Journal Title

      Biomedical Reports

      Volume: 16 Issue: 2

    • DOI

      10.3892/br.2021.1492

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival Rate and Shunt Infection Incidence Following Gastrostomy in Adult Patients with an Existing Ventriculoperitoneal Shunt2021

    • Author(s)
      MAWATARI Fumihiro、SHIMIZU Tadashi、MIYAAKI Hisamitsu、ARIMA Tetsuhiko、FUKUDA Sachiko、KITA Yoshiko、FUKAHORI Aiko、ITO Hiroyuki、MATSUKI Kei、IKEMATSU Yoshito、RYU Nobutoshi、NAKAO Kazuhiko
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 61 Issue: 12 Pages: 758-765

    • DOI

      10.2176/nmc.oa.2021-0165

    • NAID

      130008129602

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2021 Research-status Report
  • [Journal Article] Geranylgeranylacetone decreases the production of hepatitis B virus‐related antigen by comprehensive downregulation of mRNA transcription activity2021

    • Author(s)
      Haraguchi Masafumi、Miuma Satoshi、Yamamoto Kazuo、Nakao Yasuhiko、Ichikawa Tatsuki、Kanda Yasuko、Sasaki Ryu、Fukushima Masanori、Akazawa Yuko、Miyaaki Hisamitsu、Nakao Kazuhiko
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: - Issue: 7 Pages: 1-9

    • DOI

      10.1111/jgh.15394

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bile extracellular vesicles from end-stage liver disease patients show altered microRNA content2021

    • Author(s)
      Nakashiki Suguru、Miuma Satoshi、Mishima Hiroyuki、Masumoto Hiroshi、Hidaka Masaaki、Soyama Akihiko、Kanda Yasuko、Fukushima Masanori、Haraguchi Masafumi、Sasaki Ryu、Miyaaki Hisamitsu、Ichikawa Tatsuki、Takatsuki Mitsuhisa、Eguchi Susumu、Yoshiura Koh-ichiro、Nakao Kazuhiko
    • Journal Title

      Hepatology International

      Volume: 15 Issue: 3 Pages: 821-830

    • DOI

      10.1007/s12072-021-10196-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] NASH 肝生検組織を利用した線維パターンの網羅的解析によるHCC 予測2023

    • Author(s)
      宮明寿光、中尾康彦、福島真典、佐々木 龍、三馬 聡、中尾一彦
    • Organizer
      第55回日本臨床分子形態学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] デジタルパソロジーによる線維化パターン解析を用いたASH/NASH診断と発癌リスクの検討2023

    • Author(s)
      福島真典、宮明寿光、中尾一彦
    • Organizer
      第109回日本消化器病学会総会,
    • Related Report
      2023 Annual Research Report
  • [Presentation] Evaluation of histological differences between cirrhosis due to alcoholic-related liver disease and non-alcoholic steatohepatitis using automated fibrosis phenotyping of liver histology.2023

    • Author(s)
      Fukushima M, Miyaaki H, Nakao Y, Sasaki R, Miuma S, Okano S, Nakao K
    • Organizer
      EASL The International Liver Congress(第58回欧州肝臓学会),
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] デジタルパソロジーによるNAFLD肝移植レシピエント肝臓におけるHCCに特徴的な線維化パターンの解析.2022

    • Author(s)
      宮明寿光、福島真典、佐々木 龍、三馬 聡、中尾一彦
    • Organizer
      日本臨床分子形態学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] NAFLDにおけるアポトーシスシグナル解明の進歩.2022

    • Author(s)
      赤澤祐子、宮明寿光、中島正洋、中尾一彦
    • Organizer
      日本アルコール・アディクション医学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] デジタルパソロジーによる線維化パターン解析を用いたASH・NASH診断2022

    • Author(s)
      福島真典
    • Organizer
      肝類洞壁細胞研究会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝移植組織を利用した非アルコール性脂肪肝炎(NASH)の病態解析2022

    • Author(s)
      宮明寿光、江口 晋、中尾一彦
    • Organizer
      日本消化器病学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] NAFLD肝硬変におけるコラーゲン量と病態のデジタルパソロジーによる解析.2022

    • Author(s)
      宮明寿光、福島真典、佐々木 龍、 三馬 聡、中尾一彦
    • Organizer
      日本肝臓学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] デジタルパソロジーによるNAFLD肝移植レシピエント肝臓におけるHCCに特徴的な線維化パターンの解析.2021

    • Author(s)
      中村 裕、宮明寿光、中尾一彦
    • Organizer
      日本肝臓学会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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