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Analysis for small-for-size liver transplantation ; strategy for safety living donorl liver transplantation in adult

小体积肝移植分析；

基本信息

批准号：
10470250
负责人：
FURUKAWA Hiroyuki
金额：
$ 8.26万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

To investigate pathophisiology and treatment of small-for-size liver transplantation, we performed experimental and clinical studies.To investigate minimum limit of liver volume, 85% hepatectomy was performed in mice, rats, beagle dogs. These study revealed that massive hepatectomy induce TNF-α mRNA up-regulaton, increase endothelin-1 production, and augment portal vein pressure in mice, rats, and dogs, respectively. In mice experiment, TNF-a inhibitors, ONO-SM362, and TNF-α monoclonal antibody, prolonged animal survival significantly compared to untreated control. Real time PCR analysis has revealed that TNF-α mRNA expression in liver tissue was suppressed significantly by ONO-SM362 at 24hr after 85% hepatectomy. A non-selective endothelin recptor antagonist, TAK-044, was administered into 85% hepatectomized rats before surgery. The treated rats survived more than 2weeks, although the untreated rats died within 24hr after surgery. In canine experiments, although TAK-044, and another k … More ind of vasodilator, PDE III inhibitor including amrinone and milrinone, and port-caval shunt suppressed portal vein pressure and prolonged animal survival, the treatments did not get long survival more than 2weeks except one dog treated with TAK-044, which is still alive even 2year after the massive hepatectomy. Taking all things mentioned above into account, TNF-α inhibitors and vasodilators are effective for liver failure after massive hepatectomy, but further experiments are necessary to get long survivor in canine 85% hepatectomy.In clinical study, graft volume and hepatic blood flows were measured, and they were evaluated on the view point of patients prognosis after adult living donor liver transplantation (LDLT). When the portal venous flow reached the range from 150 to 250 (ml/min 100 g liver graft) after revascularization, the patients experienced fewer complications. The portal blood range correlated to over 40% graft versus standard liver volume (GV/SV) ratio. According to this clinical analysis, we recommend right lobe graft in adult LDLT, if conditions of donor are permissive. Less

为了探讨小体积肝移植的病理生理学和治疗方法，我们进行了实验和临床研究，对小鼠、大鼠、beagle犬进行了85%肝切除，以探讨小体积肝移植的最小肝体积。这些研究表明，大面积肝切除分别诱导小鼠、大鼠和狗TNF-α mRNA上调，内皮素-1产生增加，门静脉压力增加。在小鼠实验中，TNF-α抑制剂ONO-SM 362和TNF-α单克隆抗体与未处理对照相比显著延长动物存活。真实的时间PCR分析显示，在85%肝切除后24小时，ONO-SM 362显著抑制肝组织中TNF-α mRNA的表达。术前对85%肝切除大鼠给予非选择性内皮素受体拮抗剂TAK-044。治疗组大鼠存活超过2周，而未治疗组大鼠在术后24小时内死亡。在犬实验中，尽管TAK-044和另一种k ...更多信息血管扩张剂、PDE III抑制剂（包括氨力农和米力农）和门腔静脉分流术抑制了门静脉压力，延长了动物生存期，除TAK-044治疗的一只犬在大面积肝切除术后20年仍存活外，其余治疗均未获得超过20周的长期生存。因此，TNF-α抑制剂和血管扩张剂是治疗大面积肝切除术后肝功能衰竭的有效药物，但要使犬85%肝切除术后长期存活还需进一步的实验研究。血运重建后门静脉血流量达到150 ~ 250（ml/min 100 g肝移植物）时，患者并发症较少。门静脉血范围与超过40%的移植物与标准肝脏体积（GV/SV）比值相关。根据临床分析，在供体条件允许的情况下，成人肝移植宜采用右叶移植。少