Glycan Modification Analysis as a Novel Diagnostic Marker and Therapeutic Target for Non-Alcoholic Fatty Liver Disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hokkaido University
• Principal Investigator: Ogawa Koji 北海道大学, 大学病院, 助教 (20735188)
• Co-Investigator(Kenkyū-buntansha): 坂本 直哉 北海道大学, 医学研究院, 教授 (10334418) ; 須田 剛生 北海道大学, 大学病院, 特任助教 (20447460)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: NASH / 糖鎖

Outline of Final Research Achievements

The development of non-invasive diagnostic methods is urgently needed for the diagnosis and understanding of non-alcoholic steatohepatitis (NASH), as liver biopsy remains the only available diagnostic method. In this study, we performed comprehensive glycomic analysis (integrated glycomics) of serum samples from patients diagnosed with NAFL (non-alcoholic fatty liver) and NASH using a unique approach that goes beyond liver enzyme analysis. As a result, we discovered a novel serum glycan marker, AAT-A3F, which reflects liver inflammation sensitively without being correlated with liver enzyme levels. We further demonstrated that the serum AAT-A3F level correlates with the expression of inflammatory cytokines in liver cells and liver tissue inflammation, enabling the diagnosis of early-stage NASH. Our findings confirm that AAT-A3F, as a novel diagnostic and pathophysiological marker for NASH, can detect early-stage pathological changes associated with NASH progression.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝疾患は、肥満人口の増加に伴い世界的な公衆衛生上の問題となる。NAFLDは、非アルコール性脂肪肝（NAFL）と非アルコール性脂肪性肝（NASH）に分類されNAFLDの一部は、NASH、肝硬変、肝細胞癌へと進展する予後不良な病態をたどるため、早期に高リスク症例の囲い込みが必須である。この血清AAT-A3F値と既存の、診断マーカー統合し解析する事により、非侵襲的なNASH診断への開発の萌芽となりうる。