2022 Fiscal Year Final Research Report

Role of hepato-splenic interaction in portal hypertension

Research Project

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Project/Area Number	20K08998
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Yamanashi Prefectural Hospital Organization
Principal Investigator	Iimuro Yuji 地方独立行政法人山梨県立病院機構山梨県立中央病院(がんセンター局ゲノム解析センター), ゲノム解析センター, 研究員 (30252018)
Co-Investigator(Kenkyū-buntansha)	弘津陽介地方独立行政法人山梨県立病院機構山梨県立中央病院(がんセンター局ゲノム解析センター), ゲノム解析センター, チーフ研究員 (10793838) 河野寛山梨大学, 大学院総合研究部, 特任准教授 (40322127) 鈴村和大兵庫医科大学, 医学部, 講師 (50434949) 波多野悦朗兵庫医科大学, 医学部, 非常勤講師 (80359801)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	門脈圧亢進症 / 脾線維化 / 肝細胞癌 / ゲノム解析
Outline of Final Research Achievements	The purpose of this study was to elucidate the relationship between splenomegaly/splenic fibrosis in a state of portal hypertension, and the development of liver fibrosis/hepatocellular carcinoma. In the liver tissues of patients with liver cirrhosis, the accumulation of anti-inflammatory macrophages around the attenuated fibrous tissue was observed after splenectomy. In order to investigate the relationship between the accumulated macrophages and the improvement of liver fibrosis, gene expression analysis at the cellular level was attempted, but no distinctive results have been obtained thus far. On the other hand, genomic analysis of hepatocellular carcinoma that developed in patients with liver cirrhosis accompanied by splenomegaly was conducted, comparing it with hepatocellular carcinoma in non-cirrhotic cases, to determine whether there are differences in the profile of mutated genes. However, no distinctive differences have been found up to the present.
Free Research Field	肝線維化、肝発癌
Academic Significance and Societal Importance of the Research Achievements	ウイルス肝炎治療の進歩の一方で、残存する肝線維化に起因する肝発癌の抑制、門脈圧亢進状態遷延による合併症の制御などが、重要な課題として浮上しています。これまでの検討で、腫大および線維化した脾臓が肝臓の線維化および肝発癌に関与する可能性が明らかになりつつあります。今回の研究で、脾臓摘出に伴う肝組織での細胞レベルの遺伝子発現、発症肝細胞癌での変異遺伝子の特徴などを行いましたが、まだ特徴的な変化は得られていません。今後、腫瘍内微小環境などの解析を加えて検討を行い、肝臓脾臓臓器相関の研究を行う予定です。