2022 Fiscal Year Final Research Report

Analysis of nonalcoholic steatohepatitis with severe obesity and mechanism of improvement after surgery

Research Project

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Project/Area Number	20K11586
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 59040:Nutrition science and health science-related
Research Institution	Iwate Medical University
Principal Investigator	Sasaki Akira 岩手医科大学, 医学部, 教授 (40275540)
Co-Investigator(Kenkyū-buntansha)	梅邑晃岩手医科大学, 医学部, 准教授 (10749675) 石田和之獨協医科大学, 医学部, 教授 (40444004) 石垣泰岩手医科大学, 医学部, 教授 (50375002) 岩谷岳岩手医科大学, 医学部, 特任教授 (70405801)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	非アルコール性脂肪性肝炎 / 代謝異常関連脂肪肝 / 肥満症 / 2型糖尿病 / 減量・代謝改善手術
Outline of Final Research Achievements	The aim of the present study was to investigate the mechanism for improvement of liver fibrosis in non-alcoholic steatohepatitis (NASH) patients with severe obesity who underwent laparoscopic sleeve gastrectomy (LSG). In the liver biopsies during LSG, we diagnosed indeterminable nonalcoholic steatohepatitis in any patient with histopathological findings of any inflammation, hepatocyte ballooning, or liver fibrosis with steatosis < 5%. Postoperative liver biopsy was performed in 90 NASH patients, and the improvement rate of NASH was 80% at 1 year and 83% at 3 years after LSG. In lipidomic analysis of blood and liver tissue samples after LSG, 5 serum-free fatty acids were significantly decreased, while 18 were significantly increased, correlating with the effect of weight loss and the percentage of steatosis. In particular, PC (18:1e_20:4) was significantly increased in patients with NASH and may be a useful surrogate marker for the diagnosis of NASH and for therapeutic effect.
Free Research Field	内分泌代謝外科学、消化器外科学
Academic Significance and Societal Importance of the Research Achievements	高度肥満症患者に対するLSGにおいて肝組織を用いた研究は世界でも少なく、減量経過と共に経時的な肝線維化診断や肝組織のリピドミクス解析は、報告されていない。NASHと診断されたLSG患者に肝生検を外来で経時的に施行することで、肝脂肪化や線維化の改善が脂質代謝の改善により起こっていることを科学的に解明することができると考えた。またLC-MS解析では、サンプル中に含まれる既知の脂質以外にも未知な脂質構造が推定でき、高精度な定量値算出による比較も可能である。LSGを受けた患者群における肝組織のLC-MS解析例の報告はなく、高度肥満症患者の脂質代謝の変化を解明できる可能性がある。