Development of non-invasive assessment method for NASH using expired gas analysis with AI-powered gas chromatography

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19727
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: University of Shizuoka
• Principal Investigator: Ishikawa Tomohisa 静岡県立大学, 薬学部, 教授 (10201914)
• Co-Investigator(Kenkyū-buntansha): 山口 桃生 静岡県立大学, 薬学部, 助教 (30804819)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: MASH / 肝線維化 / 揮発性有機化合物 / 非侵襲的診断 / 治療薬スクリーニング

Outline of Final Research Achievements

We aimed to establish a simple non-invasive method for assessing the development of MASH through expired gas analysis and identifying volatile organic compounds (VOCs) characteristic of MASH. Using three different mouse models of liver disease with different development mechanisms, we selected discriminatory features from breath prints obtained before and after disease onset and successfully constructed a discriminatory method with high accuracy using machine learning algorithms. We also analyzed the components of VOCs in expired gas using gas chromatography-mass spectrometry and identified 15 compounds that significantly contribute to the discrimination of liver fibrosis. In the future, accumulating more data will lead to the establishment of a new screening method for MASH therapeutic drugs and the proposal of therapeutic target molecules.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

肝線維化を伴うMASHの治療薬開発は喫緊の課題であるが、現状、特異的治療薬の開発は進んでいない。その一因として、動物実験による肝線維化治療薬のスクリーニングに利用可能なMASHの簡易的な判定方法がないことが挙げられる。本研究では、呼気中VOCsの分析による簡易的なMASH進行非侵襲判定法の構築に成功した。呼気分析によるMASH判定法が確立できたことから、非侵襲的で経時的に評価が可能な治療薬スクリーニング法の開発への応用が期待できる。さらに、肝線維化やMASHに特徴的なVOCsが同定できたことから、MASH 発症に至るリスク因子やMASH 治療薬の新たなターゲット分子の提案への発展も期待できる。