Involvement of ADAMTS 13 in liver failure after hepatectomy and establishment of novel liver failure treatment strategy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10580
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nara Medical University
• Principal Investigator: Nomi Takeo 奈良県立医科大学, 医学部, 学内講師 (50570991)
• Co-Investigator(Kenkyū-buntansha): 松本 雅則 奈良県立医科大学, 医学部, 教授 (60316081)
• Research Collaborator: Obara Shinsaku
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ADAMTS13 / vWFマルチマー / 肝不全 / 虚血再灌流障害 / 肝切除 / Pringle法

Outline of Final Research Achievements

This study aimed to clarify the effect of hepatectomy on UL-VWFMs. Thirty-five patients who underwent hepatectomy were eligible for the study. Multimer analysis of plasma VWF was performed. For analyses, patients were categorized according to UL-VWFM positivity after hepatectomy. The UL-VWFMs indices were significantly increased from 0.2% (0.0%-7.8%) before the operation to 4.2% (0.1%-16.3%)on postoperative day seven after the operation (p < 0.001).Seven patients remained UL-VWFMs-negative and 22 patients became UL-VWFMs-positive after operation. By multivariable analysis, Pringle’s maneuver duration was significantly associated with increased UL-VWFMs level after hepatectomy(p = 0.043). UL-VWFMs index was significantly correlated with Pringle’s maneuver duration (r = 0.444, p = 0.017). In conclusion, Plasma UL-VWFMs levels increased after hepatectomy due to ischemia-reperfusion injury with Pringle’s maneuver.

Free Research Field

肝臓外科，腹腔鏡外科, 肝胆膵外科

Academic Significance and Societal Importance of the Research Achievements

これまでADAMTS13, vWF, VWFマルチマーと肝切除及びPringe法との関連に着目した検討は，国内外において報告がない.本研究により，UL-VWFマルチマーと術中Pringle法による虚血再灌流障害の関連が明らかにされたことで，今後，肝切除後肝不全に対する新たな治療戦略となり得る可能性が示唆される．さらに研究がすすめば，効率的な肝切除後肝不全治療戦略となる可能性がある．ADAMTS13関連因子は病的血栓との関連から心筋梗塞や脳梗塞の治療薬としての可能性も示されており，肝臓のみならず他臓器疾患への波及効果が期待される．