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Establishment of new treatment strategy for NASH by elucidating the mechanisms of fibrosis progression due to nocturnal intermittent hypoxia.

Research Project

Project/Area Number 16K09564
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe Nippon Dental University

Principal Investigator

HIRONO Haruka  日本歯科大学, 新潟生命歯学部, 准教授 (80386268)

Co-Investigator(Kenkyū-buntansha) 大越 章吾  日本歯科大学, 新潟生命歯学部, 教授 (70231199)
長谷川 勝彦  日本歯科大学, 新潟生命歯学部, 准教授 (60328870)
河野 正己  日本歯科大学, 新潟生命歯学部, 教授 (20170201)
松田 康伸  新潟大学, 医歯学系, 准教授 (40334669)
Research Collaborator WATANABE kazuhiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords非アルコール性脂肪性肝疾患 / 睡眠時無呼吸症候群 / 夜間低酸素血症 / CPAP / 非アルコール性脂肪肝炎 / 持続陽圧呼吸療法 / 低酸素血症 / 持続的陽圧呼吸療法 / NAFLD / NASH / 肝障害 / フィブロスキャン / M2BPGi / 肝線維化 / 脂肪肝
Outline of Final Research Achievements

The fatty liver disease which is not related to drinking is so called NAFLD(non-alcoholic fatty liver disease). Most of it is the simple fatty liver, not resulting in a big trouble. However, a part of it could be NASH(non-alcoholic steatohepatitis), which has mimicking pathology of alcoholic liver injury and has a potential of progression to liver cirrhosis. Though the most important cause of NAFLD is obesity, chronic intermittent nocturnal hypoxia in OSAS(obstructive sleep apnea syndrome) patients is regarded as one of the causes for NAFLD independently without obese factor.The first choice of the treatment of OSAS is CPAP(continuous positive airway pressure), resulting in improvement of nocturnal hypoxia. We demonstrated the effectiveness of CPAP therapy for hypoxic liver injury by using 50 OSAS patients with NAFLD.

Academic Significance and Societal Importance of the Research Achievements

NASHを含めたNAFLDの最も有効な治療法は減量であるが、実際に実行できることは少なく、今のところ有効な薬物療法は存在しない。NAFLDにはOSASを合併していることがあり、肝障害の原因として肥満とは別に夜間間欠的低酸素血症も肝障害の原因の一つであることが知られてきた。今回、我々はCPAPによる低酸素血症の改善がNAFLDの肝障害を有意に改善させたことを実証した。
NAFLDにおいて、まず問診にてOSASの有無を確認し、終夜睡眠ポリグラフィー(PSG)検査で陽性であれば積極的にCPAPの導入を行うことによりNAFLDの進行を抑える可能性があり、この研究の社会的意義は大きいと考える。

Report

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

    (10 results)

All 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Dental pulp cell bank as a possible future source of individual hepatocytes2018

    • Author(s)
      Ohkoshi S, Hirono H, Nakahara T, Ishikawa H.
    • Journal Title

      World J Hepatol.

      Volume: 10 Issue: 10 Pages: 702-707

    • DOI

      10.4254/wjh.v10.i10.702

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Hepatic Steatosis with Controlled Attenuation Parameter (CAP) Technology2017

    • Author(s)
      Ohkoshi S, Hirono H, Watanabe K and Hasegawa K
    • Journal Title

      Journal of Gastroenterology, Hepatology and Endoscopy

      Volume: 2 Pages: 1-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 閉塞性睡眠時無呼吸症候群と脂肪肝 -肝フィブロスキャン検査を用いたアプローチー2017

    • Author(s)
      大越章吾、廣野玄、渡邉和彦、長谷川勝彦、斎藤満美子、安井浩美
    • Journal Title

      歯学

      Volume: 105 Pages: 21-25

    • Related Report
      2017 Research-status Report
  • [Journal Article] 睡眠時無呼吸症候群における夜間間欠的低酸素血症の改善が肝線維化・脂肪化に及ぼす影響の解析2017

    • Author(s)
      廣野玄、渡邉和彦、長谷川勝彦、河野正己、大越章吾
    • Journal Title

      新潟県医師会報

      Volume: 802 Pages: 7-8

    • Related Report
      2017 Research-status Report
  • [Presentation] 夜間低酸素血症の影響を考慮にいれたNAFLDの治療指針の提案2019

    • Author(s)
      廣野 玄
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 夜間低酸素血症がNAFLDに及ぼすインパクト2018

    • Author(s)
      廣野 玄
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Differentiation of dental pulp-derived mesenchymal stem cells into hepatocytes and their repopulation in nude rat liver.2018

    • Author(s)
      Ohkoshi S
    • Organizer
      26th United European Gastroentetrology Week, Vienna
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] いびき症に潜む動脈硬化危険因子 ~睡眠から発する検診メッセージ~ (肝フィブロスキャン検査を用いたアプローチ)2018

    • Author(s)
      廣野玄、渡邉和彦、長谷川勝彦、大越章吾、河野正己
    • Organizer
      2017年度 新潟市医師会地域医療研究助成発表会
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Presentation] 睡眠時無呼吸症候群(SAS)と脂肪肝の関係 ~フィブロスキャンを用いて~2017

    • Author(s)
      廣野玄、渡邉和彦、長谷川勝彦、大越章吾、猪子芳美、河野正己
    • Organizer
      第14回 新潟睡眠呼吸障害研究会
    • Related Report
      2017 Research-status Report
  • [Book] 専門医から伝えたい 歯科医院に知ってほしい 肝疾患のこと2019

    • Author(s)
      大越 章吾
    • Total Pages
      112
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2018 Annual Research Report

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

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