Progressing factors of nonalcoholic fatty liver disease (NAFLD) by gene analysis of serial liver biopsies.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kanazawa University
• Principal Investigator: TAKESHITA YUMIE 金沢大学, 医学系, 准教授 (40507042)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 非アルコ－ル性脂肪性肝疾患

Outline of Final Research Achievements

Tofogliflozin and, to a lesser degree, glimepiride significantly reduced the score of liver histology for 48 weeks in participants with liver biopsy specimen-confirmed NAFLD and type 2 diabetes, with no significant difference between the agents under a similar reduction in glucose levels. The percentage of participants in the tofogliflozin group who had an improvement in the fibrosis stage after 48 weeks in this trial was 60%. The tofogliflozin-mediated improvement in the fibrosis stage in the current study is greater than that of past reported treatment. The reduction in steatosis scores was significantly associated with the tofogliflozin-mediated reduction in HbA1c and weight. On the other hand, reduction in fibrosis scores was significantly associated with HbA1c at baseline and the tofogliflozin-mediated glycemic control but not the weight reduction. These findings suggest that glycemic control, rather than weight reduction, contributes to liver fibrosis alleviation.

Free Research Field

内分泌・代謝内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、糖尿病治療薬が、糖尿病を改善するだけでなく、線維化を含めたNAFLDの組織像を改善させることを示した。他施設では、消化器領域で肝臓病理の研究を、代謝領域で臓器特異的インスリン感受性の研究を行なうなど、領域が分かれて研究を行なっている。本研究では、領域を統合して解析し、前向き研究で行った介入試験の症例を対象に、肝臓病理・糖代謝の変化との関連性を明らかにし、NAFLDを有する糖尿病患者の肝臓病理を改善する作用点を明らかにすることができた。