Research for investigating treatment of fulnilnant hepatic failure : An experimental study of auxiliary temporal partial orthotopic liver transplantation using living-donor partial liver

全面性肝衰竭治疗研究：活体部分肝辅助颞部部分原位肝移植的实验研究

• 批准号: 08557078
• 负责人: NAKANO Hiroshi
• 金额: $ 6.27万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557078/
• 关键词: fulminant hepatic failure; α-glutathione S transferase; choline-methionine deficient diet; N-acetylcysteine; reduced glutathione; anti-intercellular adhesion molecule; auxiliary temporal partial orthotopic liver transplantation; N-acetylcysteine

(Background and Aim) Fulminant hepatic failure has been a fatal disease and has had an extremely poor prognosis. However, prognosis of fulminant failure was recently improved up to 50% of survival after orthotopic liver transplantation. An alternative, auxiliary temporal partial orthotopic liver transplantation (ATPOLT), is mole useful since ATPOLT can allow two liver transplantations and can avoid immunosuppression therapy after recovery of patients. To introduce ATPOLT for fulminant hepatic failure in Japan, living-related partial liver should be introduced. The aim of the present study was to investigate what kinds of supporting therapy are needed for ATPOLT using living-related liver in pigs.(Materials and Methods) Pigs were fed a choline-methionine deficient diet for 2 months. Then, the common bile duct was ligated through laparotomy. A fulminant hepatic failure model was produced 1 week after bile duct ligation (Recipient pigs). The living-related partial left lobe liver was proc … More ured from normal pigs (Donor pigs). ATPOLT was immediately performed for the recipient pigs according to the method of Boudjema et al. In Group A (n = 5), no treatment was added after ATPOLT. In Group B (n = 5), a free radical scavenger, N-acetylcysteine (150 mg/kg/day) and anti-intercellular adhesion molecule 1 monoclonal antibody (0.8 mg/kg/day) were administered day by day after ATPOLT.(Results) In Group A, all pigs died on 3 days after ATPOLT. In Group B, all pigs survived during 3 days after ATPOLT. Serum α-glutathione S transferase concentration, which can indicate hepatocellular injury just before a few hours, was significantly higher in Group A than in Group B after the postoperative day 2 (p<0.05). Prothrombin time, concentrations of serum total bilirubin, that of serum reduced glutathione were significantly improved in Group B than in Group B.(Conclusion) As shown in Group A, ATPOLT could not result in long-term survival in pigs with fulminant hepatic failure. However, immediate treatment using the free radical scavenger and the monoclonal antibody inhibiting adhesion between neutrophils and endothelial cells can inhibit non-function of the graft liver and can allow long-term survival of the animals with fulminant hepatic failure. Less

（背景和目的）暴发性肝衰竭是一种致命的疾病，预后极差。然而，最近，原位肝移植术后暴发性衰竭的预后提高了50%。另一种选择，辅助颞部原位肝移植（ATPOLT），更有用，因为ATPOLT可以允许两次肝移植，并且可以避免患者康复后的免疫抑制治疗。为了在日本引入ATPOLT治疗暴发性肝衰竭，应该引入与活体相关的部分肝。本研究的目的是探讨使用猪活体肝脏进行ATPOLT需要什么样的支持治疗。（材料与方法）饲喂缺乏胆碱-蛋氨酸饲粮2个月。然后开腹结扎胆总管。在胆管结扎1周后建立暴发性肝衰竭模型（受体猪）。从正常猪（供体猪）上切除与活体相关的部分左叶肝。立即按照Boudjema等人的方法对受体猪进行ATPOLT。A组（n = 5）， ATPOLT后不加药。B组（n = 5）， ATPOLT后每天给予自由基清除剂n -乙酰半胱氨酸（150 mg/kg/day）和抗细胞间粘附分子1单克隆抗体（0.8 mg/kg/day）。（结果）A组猪在ATPOLT后3 d全部死亡。B组猪在ATPOLT后3 d全部成活。a组术后第2天血清α-谷胱甘肽S转移酶（α-谷胱甘肽S转移酶）浓度显著高于B组（p<0.05）。B组凝血酶原时间、血清总胆红素浓度、血清还原性谷胱甘肽浓度显著高于B组。（结论）A组显示，ATPOLT不能使暴发性肝衰竭猪长期存活。然而，立即使用自由基清除剂和抑制中性粒细胞与内皮细胞粘附的单克隆抗体进行治疗，可以抑制移植物肝脏的非功能，并允许暴发性肝衰竭动物的长期生存。少

项目成果

Kim Y-K, Nakano H, et al.: "Prediction of postoperative decompensated liver function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases"Br J Surg. 84. 793-7

Kim Y-K、Nakano H 等人：“锝 99m 半乳糖基人血清白蛋白肝脏闪烁显像对肝细胞癌合并慢性肝病患者术后失代偿性肝功能的预测”Br J Surg。

Nakano H, et al.: "Liver scintigraphy is useful for selecting candidates for preoperative transarterial chemoembolization among patients with hepatocellular carcinoma and chronic liver disease"Am J Surg. 178. 385-389 (1999)

Nakano H 等人：“肝脏闪烁扫描对于在肝细胞癌和慢性肝病患者中选择术前经动脉化疗栓塞的候选者非常有用”Am J Surg。

Nakano H,et al.: "Augmentation of mitochondrial reduced glutathione by s-adenosyl-l-methionine in ischemia-reperfusion injury of the rat steatotic liver" Eur.Surg.Res. 30. 34-42 (1998)

Nakano H 等人：“在大鼠脂肪肝缺血再灌注损伤中通过 s-腺苷-L-甲硫氨酸增强线粒体还原型谷胱甘肽”Eur.Surg.Res。

Nakano H,et al.: "N-acetylcysteine and anti-ICAM-1 monoclonal antibody reduce ischemia-reperfusion injury of the rat steatoic liver" Transpl.Proc.30. 3763 (1998)

Nakano H 等人：“N-乙酰半胱氨酸和抗 ICAM-1 单克隆抗体可减少大鼠脂肪肝的缺血再灌注损伤”Transpl.Proc.30。

Nakano H,et al.: "Prediction of postoperative decompensated liver function by technetium 99m galactosyl human serum albumin liver scintigraphy in patients with hepatocellular carcinoma complicated with chronic liver diseases." British Journal of Surgery.

Nakano H等人：“锝99m半乳糖基人血清白蛋白肝脏显像对肝细胞癌合并慢性肝病患者术后肝功能失代偿的预测”。