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

为了探讨小体积肝移植的病理机制和治疗方法，我们进行了实验和临床研究。为了研究小鼠、大鼠、比格犬85%肝切除的最小肝体积。这些研究表明，大范围肝切除分别诱导小鼠、大鼠和狗的肿瘤坏死因子-α基因表达上调，内皮素-1的产生增加，门静脉压力增加。在小鼠实验中，肿瘤坏死因子-a抑制剂、ONO-SM362和肿瘤坏死因子-α单抗与未经处理的对照组相比，显著延长了动物的存活时间。实时定量聚合酶链式反应分析显示，在85%肝切除后24小时，ONO-α显著抑制肝组织中肿瘤坏死因子-SM362的表达。85%肝切除大鼠术前给予非选择性内皮素受体拮抗剂TAK-044。尽管未经处理的大鼠在手术后24小时内死亡，但经处理的大鼠存活了两周以上。在犬的实验中，尽管Tak-044和另一个k…血管扩张剂、PDEⅢ抑制剂氨力农和米力农、门腔分流术均能抑制门静脉压力，延长动物存活时间，除1只应用TAK-044治疗的犬在大范围肝切除后2年仍存活外，其余治疗均未超过2周。综上所述，肿瘤坏死因子-α抑制剂和血管扩张剂对大范围肝切除后的肝功能衰竭是有效的，但要想在犬85%的肝切除模型上获得长期存活，还需要进一步的实验。门静脉血流量在150~250(ml/min，100g肝移植)时，并发症较少。门静脉血流范围与超过40%的移植物与标准肝体积(GV/SV)比率相关。根据这一临床分析，如果供体条件允许，我们建议在成人LDLT中进行右叶移植。较少

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