|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 2000 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥3,800,000 (Direct Cost : ¥3,800,000)
Fiscal Year 1998 : ¥5,800,000 (Direct Cost : ¥5,800,000)
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
kind 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