Expanding the donor pool

The shortage of liver grafts results in the fact that 8% of potential recipients die before receiving a graft. Liver graft division has therefore been proposed to maximize the current available liver graft pool. However, the question of benefit or additional risk for the recipients that this technique might carry remains unanswered. The European Split Liver Registry was opened in March 1993 and reviewed retrospectively the clinical experience obtained at nine European centers regarding the use of split liver transplants, during the five year period from March 1988 to March 1993. From 50 donors livers, 100 grafts were prepared: 2 grafts were discarded and the other 98 were transplanted in 53 children (2 times in 3 children) and 42 adults (2/42 heterotopic position). Sixty-three grafts were implanted in an urgent recipient (half of whom had acute hepatic failure). Portal vein thrombosis, hepatic artery thrombosis, biliary complications and retransplantation rates were 4%, 11.5%, 18.7% and 18.7% respectively. Most of these complications were unrelated to the technique itself. Actual 6 month graft survivals of elective and urgent orthotopic transplants were 80% and 61.3% in children, and 72.2% and 55.6% in adults; actual 6 month patient survivals rates for similar groupings were 88.9% and 61.1% and 80% and 67.7% respectively. Similar rates were reported after conventional transplant in Europe. It is concluded that split liver transplantation is an efficient transplant technique that benefits both urgent patients who otherwise could have died before getting a graft in time and elective patients. The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean ± SD; 5.3 ± 1.7 days) whereas all six without PHVS died within 3 days (1.8 ± 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 ± 1.2 mmHg and 16.9 ± 3.1 mmHg respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7, during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation. Hyperacute rejction of vascularized porcine to primate xenografts is initiated by the binding of xenoreactive natural antibodies to donor endothelium. We tested the hypothesis that the level of xenoantigen exnoantigen expression varies in the population of potential poricine donors and may determine the amount of binding of xenoreactive natural antibodies to a porcine organ perfused by xenogeneic blood. Two hundred ninety pigs were studied using an inhibition ESISA that quantitated the xenoantigen level on porcine platelets. Based on this assay, the levels of xenoantigen expression in the population adhered to a normal distribution. Kidneys from pigs found to express high antigen levels and kidneys from pigs found to expres high antigen levels and kidneys from pigs found to express low antigen levels were perfused with baboon blood using an extracorporeal circuit. In multiple experiments, a significant difference was observed in the amount of xenoreactive natural antibody adsorbed by high antigen versus low antigen organs. Normalizing for the weight of the perfused organs fro levels of natural antibody in individual baboons, high antigen organs adsorbed 3.6 ± 1.3 U of xenoreactive natural antibody/g and low antigen organ adsorbed −0.8± 1.0U of xenoreactive natural antibody/g (p<0.002). lmmunopathology of tissues from the perfused organs demonstrated more deposition of 1gM and C4 in high than in low xenoantigen organs. The quantitative relationship between binding of xenoreactive natural antibodies to platelets and to whole organs suggests that platelets are a valid representation of endothelial cell antigen expression in vivo. Despite the probable importance of Galα(1-3( Gal as an epitope recognized by xenoreactive natural antibodies, differences in the binding to platelets or to organs of the GS-I-B4 lectin that recognizes that sugar had no correlation with the differences in binding of 1gM to these tissues. Variation in expression of xenoantigen may be exploited to selectively breed donors for xenotransplanmtation that are less susceptible to attack by xenoreactive natural antibodies.