Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts-regardless of recipient age-have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants. Liver Transpl 12:972-978, 2006.
In 1972, J. Woodland Hastings and colleagues predicted the existence of a proton selective channel (HV1) that opens in response to depolarizing voltage across the vacuole membrane of bioluminescent dinoflagellates and conducts protons into specialized luminescence compartments (scintillons), thereby causing a pH drop that triggers light emission. HV1 channels were subsequently identified and demonstrated to have important functions in a multitude of eukaryotic cells. Here we report a predicted protein from Lingulodinium polyedrum that displays hallmark properties of bona fide HV1, including time-dependent opening with depolarization, perfect proton selectivity, and characteristic ΔpH dependent gating. Western blotting and fluorescence confocal microscopy of isolated L. polyedrum scintillons immunostained with antibody to LpHV1 confirm LpHV1’s predicted organellar location. Proteomics analysis demonstrates that isolated scintillon preparations contain peptides that map to LpHV1. Finally, Zn2+ inhibits both LpHV1 proton current and the acid-induced flash in isolated scintillons. These results implicate LpHV1 as the voltage gated proton channel that triggers bioluminescence in L. polyedrum, confirming Hastings’ hypothesis. The same channel likely mediates the action potential that communicates the signal along the tonoplast to the scintillon.
Children transplanted for acute liver failure (ALF) urgently require an optimal graft. Lower post-transplant survival compared to children transplanted for chronic liver disease. Over 10 years, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type (ABO incompatible grafts (ABOI), Large for size grafts(XL)(GRWR>5%),deceased donor segmental liver transplantation(DDSLT), living donor liver transplantation (LDLT) and whole liver transplant (WLT) were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. 12/33 received ABOI, 5 XL grafts, 18 DDSLT, and 3 LDLT. Waiting time pre-transplant was 2.1 days. 1 and 3 year patient survival ALF group was 93% and 93% and graft survivals were 93 and 78.6%. Median follow-up was 1452 days. ABOI one and three year patient and graft survival in the ALF was 92 and 75%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group nor the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, large for size grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival not significantly different than that for non-acute liver disease.
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