Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.

T cell suppression prevents acute cellular rejection but causes life-threatening infections and malignancies. Previously, liver transplant (LTx) rejection in children was associated with the single-nucleotide polymorphism (SNP) rs9296068 upstream of the HLA-DOA gene. HLA-DOA inhibits B cell presentation of antigen, a potentially novel antirejection drug target. Using archived samples from 122 white pediatric LTx patients (including 77 described previously), we confirmed the association between rs9296068 and LTx rejection (p = 0.001, odds ratio [OR] 2.55). Next-generation sequencing revealed that the putative transcription factor (CCCTC binding factor [CTCF]) binding SNP locus rs2395304, in linkage disequilibrium with rs9296068 (D' 0.578, r(2) = 0.4), is also associated with LTx rejection (p = 0.008, OR 2.34). Furthermore, LTx rejection is associated with enhanced B cell presentation of donor antigen relative to HLA-nonidentical antigen in a novel cell-based assay and with a downregulated HLA-DOA gene in a subset of these children. In lymphoblastoid B (Raji) cells, rs2395304 coimmunoprecipitates with CTCF, and CTCF knockdown with morpholino antisense oligonucleotides enhances alloantigen presentation and downregulates the HLA-DOA gene, reproducing observations made with HLA-DOA knockdown and clinical rejection. Alloantigen presentation is suppressed by inhibitors of methylation and histone deacetylation, reproducing observations made during resolution of rejection. Enhanced donor antigen presentation by B cells and its epigenetic dysregulation via the HLA-DOA gene represent novel opportunities for surveillance and treatment of transplant rejection.

In vitro fertilization: an unexpected finding in a cohort of patients with biliary atresia.

In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.

Allospecific CD154+ T cells associate with rejection risk after pediatric liver transplantation.

Antigen-specific T cells, which express CD154 rapidly, but remain untested in alloimmunity, were measured with flow cytometry in 16-h MLR of 58 identically-immunosuppressed children with liver transplantation (LTx), to identify Rejectors (who had experienced biopsy-proven rejection within 60 days posttransplantation). Thirty-one children were sampled once, cross-sectionally. Twenty-seven children were sampled longitudinally, pre-LTx, and at 1-60 and 61-200 days after LTx. Results were correlated with proliferative alloresponses measured by CFSE-dye dilution (n = 23), and CTLA4, a negative T-cell costimulator, which antagonizes CD154-mediated effects (n = 31). In cross-sectional observations, logistic regression and leave-one-out cross-validation identified donor-specific, CD154 + T-cytotoxic (Tc)-memory cells as best associated with rejection outcomes. In the longitudinal cohort, (1) the association between CD154 + Tc-memory cells and rejection outcomes was replicated with sensitivity/specificity 92.3%/84.6% for observations at 1-60 days, and (2) elevated pre-LTx CD154 + Tc-memory cell responses were associated with significantly increased incidence (p = 0.02) and hazard (HR = 7.355) of rejection in survival/proportional hazard analysis. CD154 expression correlated with proliferative alloresponses (r = 0.835, p = 7.1e-07), and inversely with CTLA4 expression of allospecific CD154 + Tc-memory cells (r =-0.706, p = 3.0e-05). Allospecific CD154 + T-helper-memory cells, not CD154 + Tc-memory, were inhibited by increasing Tacrolimus concentrations (p = 0.026). Collectively, allospecific CD154 + T cells provide an estimate of rejection risk in children with LTx.

In vitro fertilization: an unexpected finding in a cohort of patients with biliary atresia

In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.

Solitary pancreas transplantation. Experience with 62 consecutive cases.

OBJECTIVE: To determine the safety and efficacy of solitary pancreas transplantation in the treatment of IDDM. RESEARCH DESIGN AND METHODS: A single-center retrospective case series of 62 consecutive solitary pancreas transplants (20 sequential pancreas after kidney, 42 pancreas transplants alone) performed in 57 adult IDDM patients was studied. Indications for solitary pancreas transplantation were 1) the presence of two or more overt diabetic complications and/or 2) glucose hyperlability with hypoglycemic unawareness and impaired quality of life. The recipient group consisted of 31 men and 26 women with a mean age of 38 years (range 25-62) and a mean duration of diabetes of 26 years (range 14-52). Mean pretransplant glycohemoglobin level was 9.9 +/- 2.6%. Organ acceptance was restricted to ideal donors and man-dated a minimum of a two-antigen match (mean human leukocyte antigen ABDR match 2.7). The mean cold ischemia time was 16.6 h. Whole-organ pancreas transplantation was performed with bladder drainage by the duodenal segment technique. All patients were managed with either triple or quadruple immunosuppression. Monitoring included prospective urine cytology as well as cystoscopic transduodenal needle biopsies. RESULTS: The mean length of initial hospital stay was 18 days, and mean hospital charges were $106,341. The incidences of rejection, infection, and surgical complications were 70, 55, and 47%, respectively. Overall patient and graft survival rates were 86 and 52%, respectively, with a mean follow-up of 28 months. All patients with functioning grafts had excellent metabolic control (mean glycohemoglobin level 5.1%) and achieved good rehabilitation. CONCLUSIONS: Despite morbidity, solitary pancreas transplantation can be performed with improving success, can enhance quality of life, and can offer an opportunity to arrest secondary diabetic complications.

Cytokines and cell surface receptors as target end points of immunosuppression with cyclosporine A.

Targets of cyclosporine (CsA) were identified from an array of stimulated lymphocyte responses (sLR) comprising 34 stimulation conditions in whole blood from 3 normal human volunteers (NHV) containing clinically relevant CsA concentrations (0-1200 ng/ml) in vitro. In whole blood from 5 additional NHV, selected targets (intracellular interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-alpha], and interferon-gamma [IFN-gamma]) were measured in phorbol myristate acetate (PMA)-ionomycin-stimulated T lymphocytes. Effect:concentration relationships were analyzed with E(max) pharmacodynamic (PD) equations and expressed as the concentration associated with one-half maximal inhibitory effect (EC(50)). CsA demonstrated a rich matrix of inhibitory effects on T cells (CD3(+)), B cells (CD19(+)), dendritic cells (DC) (CD11c(+)), and basophils (CD123(+)) but not on monocytes (CD14(+)) (n = 3). PD analyses suggested that the EC(50) of CsA (1) for IL-2 in CD3(+) cells in NHV (n = 8) was similar to the EC(50) demonstrated by us previously in CD4(+) cells from transplanted patients (n = 13) (EC(50) = 260 ng/ml vs. 249 ng/ml), (2) for each cytokine was different under identical stimulation conditions (TNF-alpha, 324 ng/ml; IFN-gamma, 504 ng/ml), and (3) was relatively constant for a given cytokine under different stimulation conditions (e.g., PMA-ionomycin or the staphylococcal enterotoxin B [SEB] superantigen). In conclusion, inhibition of cytokine targets by CsA is concentration dependent. Further, a given CsA concentration may produce similar inhibitory effects across different stimulation conditions. Measurement of cytokine target expression may, therefore, allow effect-controlled administration of CsA during clinical transplantation.

Humoral graft-versus-host disease after pancreas transplantation with an ABO-compatible and Rh-nonidentical donor. Case report and a rationale for preoperative screening.

Severe hemolysis and graft ischemia complicating solitary pancreas transplantation with an ABO-compatible, Rh-negative, anti-D-positive donor to Rh-positive recipient is described in this article. A brief review of the literature is presented. A rationale for preoperative screening for red cell antibodies during solid organ transplantation in this special setting is discussed.

Procurement and preparation of human isolated small intestinal grafts for transplantation.

We have developed a donor operation that incorporates en bloc removal of the liver and intestine with a limited surgical resection in vivo. Over the past 18 months, we have used the following technique for the retrieval and preparation of seven isolated small intestinal allografts. The donor operation and bench preparation can be divided into three phases. During the first phase, the small intestine is removed with the liver, pancreas, and an aortic segment. In the second phase performed ex vivo, the donor liver can be separated from the specimen. The third phase involves additional bench dissection to yield an isolated intestinal allograft. The principle advantage of this technique is that it reduces potential liver injury by minimizing the surgical dissection required in vivo. Also, dividing the liver from the intestine ex vivo allows the organs to be separated in a bloodless field under controlled conditions that may be especially important when two different surgical teams are involved.

Combined liver/small bowel transplantation using a blood group compatible but nonidentical donor.

A successful liver/small intestinal transplantation with a blood group O donor to a blood type A recipient is described. Mild graft versus host disease developed, manifested by hemolysis, but did not result in graft loss or patient mortality. This suggests that minor ABO incompatibility may be tolerated with intestinal transplantation, despite the transplantation of large amounts of lymphoid tissue.

Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine+rapamycin regimen.

BACKGROUND: Clinically, cyclosporine (CSA, Neoral) is titrated to concentrations, and not to pharmacological effect. METHODS: Intracellular interleukin- (IL) 2 was measured in phorbol myristic acid-ionomycin-stimulated peripheral lymphocytes by flow cytometry, after isolation from 14 renal transplant recipients receiving CSA+prednisone, and double-blind rapamycin (rapamycin:placebo=4:1). RESULTS: The proportion (%) of CD4+IL-2+ lymphocytes corresponding to CSA levels (mean+/-SD ng/ml) measured preoperatively (TO=O), and on postoperative day 8, before (356+/-63), and 2 hr after the morning dose (Cmax=1567+/-669), decreased from 39+/-16 to 15+/-8 and 3+/-1.6, respectively. Reciprocally, unresponsive lymphocytes (%CD4+IL-2-) increased with increasing CSA levels and predicted an EC50 of 249 ng/ml (CSA concentration at which CD4+IL-2- cells increased by 50% over baseline) in an Emax pharmacodynamic model. CONCLUSIONS: Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.

Experience with protocol biopsies after solitary pancreas transplantation.

The early detection of allograft rejection remains elusive after solitary pancreas transplantation (PTX). We have previously described a modified technique of cystoscopic transduodenal PTX biopsy using the Biopty gun under ultrasound guidance. During the last 2 years, we performed 24 solitary PTXs with prospective protocol biopsy monitoring as well as biopsies performed whenever clinically indicated. The study group included 17 pancreas transplants alone, 6 sequential pancreas after kidney transplants, and 1 sequential pancreas after liver transplant. Five patients received pancreas retransplants. A total of 92 cystoscopically directed core PTX biopsies were performed, including 50 protocol biopsies (mean 2.1 per patient). Protocol biopsies were performed at 1 month (19), 2 months (3), 3 months (20), 6 months (7), and 12 months (1) after PTX. Adequate PTX tissue for histopathologic examination was obtained in 49 cases (98%). Biopsy findings included no rejection (34), mild rejection (13), pancreatitis (1), and cytomegalovirus infection (1). Overall, 15 of the 49 evaluable biopsies (31%) had significant histopathologic findings. All but 1 of the cases of mild rejection were treated with bolus steroids. Eight of these patients subsequently developed recurrent biopsy-proven rejection within 2 months; 5 grafts were subsequently lost to rejection between 3 and 13 months after PTX. Three biopsy complications occurred: 1 hematoma, 1 pancreatitis, and 1 ileus. Patient survival is 96% and PTX graft survival (complete insulin independence) is 75% after a mean follow-up of 15 months. In the remaining 42 clinically indicated biopsies, 3 were insufficient, 8 showed no rejection, and 31 (79%) had rejection. In half of these cases, the rejection was graded as moderate to severe. In conclusion, prospective monitoring with protocol PTX biopsies may result in the earlier detection of allograft rejection and have a direct effect on improving results after solitary PTX.

Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.

AIMS: The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease. RESULTS: Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21). CONCLUSIONS: SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.

Patch aortotomy for aortic valve replacement after previous coronary artery bypass grafting.

Exposure for aortic valve operations after previous coronary artery bypass grafting may be technically difficult owing to the presence of patent vein grafts on the proximal aorta. A patch or "island" aortotomy technique that allows excellent exposure of the aortic valve is presented here. In select patients this approach may facilitate cardioplegia administration.

Long term management of liver transplant rejection in children.

The current management of hepatic allograft rejection after liver transplantation in children requires effective baseline immunosuppression to prevent rejection and rapid diagnosis and treatment to manage acute rejection episodes. The subsequent impact on chronic rejection is dependent on the combination of adequate prevention and the treatment of acute rejection. Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Introduced in 1989, tacrolimus was first used in the salvage of refractory acute or chronic rejection under cyclosporin or to rescue patients with significant cyclosporin-related complications. The majority of paediatric transplant centres use a combination of steroids with tacrolimus as a basic immunosuppressant regimen following paediatric liver transplantation. This combination has allowed the acute cellular rejection-free rate to increase to between 30 and 60%, while lowering the rate of refractory rejection to less than 5%. Corticosteroid-resistant rejection is commonly treated with monoclonal (muromonab CD3) or polyclonal preparations. Although most episodes of acute cellular rejection occur during the first 6 weeks after liver transplant, the appearance of late acute liver allograft rejection must raise the question of noncompliance, especially in the adolescent population. Chronic rejection is becoming increasingly rare under tacrolimus-based immunosuppression. Tacrolimus is effective in reversing refractory acute cellular rejection or early chronic rejection in patients initially treated with cyclosporin-based regimens. Patients with a history of noncompliance as well as children with autoimmune liver disease are at risk of chronic rejection. Retransplantation therapy for chronic rejection has, fortunately, become more rare in the tacrolimus era with only 3% of retransplants being performed for this indication. Newer immunosuppressive agents are further modifying the long term management of liver allograft rejection. These include mycophenolate mofetil, rapamycin and IL-2 antibodies such as daclizumab. The development of these agents is allowing patient-specific immunosuppressive management to minimise rejection as well as the complications related to immunosuppression.

Experience with enteric conversion after pancreatic transplantation with bladder drainage.

BACKGROUND: Bladder drainage by the duodenal segment technique is currently the preferred method of handling the exocrine secretions after vascularized pancreatic transplantation. Despite improving results, however, the management of metabolic and urologic complications associated with bladder drainage remains problematic. STUDY DESIGN: A retrospective survey was performed of a consecutive case series of 196 pancreatic transplantations in 186 patients with diabetes over an 80-month period. All patients underwent whole organ pancreatic transplantation with bladder drainage by the duodenal segment technique. RESULTS: A total of 25 conversions (13 percent) from bladder drainage to enteric drainage were performed in 24 patients (24 side-to-side duodenoenterostomies, one Roux-en-Y limb duodenoenterostomy). The mean time of enteric conversion after pancreatic transplantation was 22 +/- 18 months (range, 1 to 72 months). All but two of the enteric conversions were performed at least 6 months after pancreatic transplantation. Indications for enteric conversion included dehydration with intractable metabolic acidosis (n = 18; 9 percent), urologic complications (n = 5; 3 percent), or problems with the duodenal segment (n = 2; 1 percent). The mean length of hospitalization for enteric conversion was 12 +/- 7 days (range, 6 to 30 days). All patients experienced improvement in their symptoms after enteric conversion. Anastomotic leaks developed postoperatively in five patients; two were managed operatively and three were managed nonoperatively. Oral bicarbonate supplementation was eliminated in all but one patient after enteric conversion. Patient survival is 100 percent and pancreatic graft survival (insulin independence) is 96 percent after a mean follow-up of 22 months after enteric conversion. CONCLUSIONS: Enteric conversion after pancreatic transplantation with bladder drainage is a safe and effective therapy for refractory problems related to the duodenal segment, altered physiologic function, or urologic complications and should be considered after 6 months for patients with persistent side effects.

Duodenal segment complications in vascularized pancreas transplantation.

Bladder drainage by the duodenal segment (DS) technique is currently the preferred method of pancreas transplantation (PTX) but is associated with unique complications. Over a 7-year period, 191 diabetic patients underwent 201 whole-organ PTXs with bladder drainage using a 6 to 8 cm length of DS as an exocrine conduit. A retrospective chart review was performed to document all DS morbidity. DS complications occurred in 38 cases (19%). Twelve patients developed DS leaks and required operative repair. DS bleeding was documented in 26 cases, necessitating cystoscopy in 22 patients and open repair in eight patients for significant hematuria. Cytomegalovirus (CMV) duodenitis was diagnosed in seven cases, with four presenting as DS leaks and three with hematuria. Five patients experienced ampullary obstruction early after PTX. Rejection of the DS was confirmed by biopsy in 13 patients, including eight cases of acute and five cases of chronic rejection. Two patients had stone formation from the DS staple line. Enteric conversion was performed in five patients for DS abnormalities (leaks in 2 cases, bleeding in 2, and CMV duodenitis in 1). Among patients with DS complications, patient survival is 84% and pancreas graft survival is 68% after a mean follow-up of 44+/-12 months. Complications related to the DS remain an important source of morbidity but rarely cause death after PTX. In spite of unique side effects, transplantation of the DS remains an acceptable alternative for exocrine drainage after PTX.

Factor V inhibitor in a liver transplant patient associated with porcine xenoperfusion.

The development of a high-titer factor V inhibitor is described in a patient who underwent orthotopic liver transplantation followed by porcine xenoperfusion after an acute rejection episode. The inhibitor showed no cross-reactivity to either porcine or bovine factor V, nor was it accessible to human platelet factor V. The limitations of treatment modalities including intravenous immunoglobulin, steroids, cytotoxic therapy, intense plasmapheresis and platelet transfusions are discussed.

Sirolimus in pediatric transplant recipients.

The side effects of calcineurin inhibitors (CI) have a unique spectrum in pediatric recipients of organ transplants. These include a lifelong risk of mortality due to sepsis, a nearly 5% risk of renal failure from protracted exposure to CI, and a significantly higher risk of posttransplant lymphoproliferative disorder (PTLD) when compared with adults (10% versus 2%). This led us to explore the use of the new antiproliferative immunosuppressant sirolimus (SRL) for rescue and primary immunosuppression in recipients of pediatric abdominal and thoracic organs at the Children's Hospital of Pittsburgh. Following initial success with SRL in 50 such children, we also explored its use for the elimination of tacrolimus (TAC) in patients experiencing toxicity and for maintenance immunosuppression in steroid-sparing regimens in liver transplantation. These early results suggest that sirolimus may hold promise as a primary immunosuppressive agent under defined protocol conditions. The salient features of our experience with SRL in over 85 children are summarized here.

Split-liver transplantation: a comparison of ex vivo and in situ techniques.

BACKGROUND/PURPOSE: The expanding applicability of liver transplantation as treatment for end-stage liver disease has fostered a disproportionate increase in liver transplant candidates in the face of an unchanging pool of donor organs. This has resulted in disparities in pretransplant waiting times and deaths. The splitting of a liver allograft allows for the transplantation of 2 recipients, usually an adult and a child, thus providing a means to expand the cadaveric donor pool. METHODS: The authors present their results on the performance of an ex vivo (back table) split and in situ (in a hemodynamically stable cadaveric donor) split to evaluate safety, applicability, and effectiveness. Between November 1989 through April 1998, 54 split-liver transplant recipient operations were performed (24 pediatric and 30 adult). Thirty donors were procured: the ex vivo splitting yielded 25 grafts from 13 donors (donor age, 24.6+/-11 years), and the in-situ technique yielded 29 grafts from 17 donors (mean donor age of 25.5+/-10.4 years). Five donors involved interinstitutional sharing for which the left side of the graft was kept at the host hospital and the right side grafts were utilized at our center. RESULTS: Overall 1-year patient survival was 85%, with a graft survival of 72%. Patient survival was similar with ex vivo (74%) as compared with the in situ splitting group (96%; P = .06), as was graft survival in ex vivo (61 %) versus in situ (81%) splitting (P = .15). The pediatric population benefited most from the in situ technique, with a 1-year patient survival rate of 100% with the in situ technique versus the ex vivo technique survival rate of 64% at 1 year (P = .02). The 1-year graft survival comparing these 2 techniques was 83% for the in situ group versus 45% for the ex vivo group. Analysis of the program evolution of split-liver transplantation suggested a time-dependent learning curve, which was applicable to surgical splitting technique, implantation, and recipient selection. CONCLUSIONS: The principle of splitting livers from cadaveric donors is fundamentally sound and technically feasible. The authors' outcomes analysis using 2 different procurement techniques suggests that the in situ technique is clinically efficacious, can be used alternatively with the ex vivo technique, and is comparable to whole-liver allograft transplantation.

Impact of segmental grafts on pediatric liver transplantation--a review of the United Network for Organ Sharing Scientific Registry data (1990-1996).

PURPOSE: The aim of this study was to assess the relative impact of segmental grafts from cadaveric and living donors on outcomes in 3,409 pediatric transplants (<18 years) between 1990 and 1996. METHODS: Analysis of the United Network for Organ Sharing (UNOS) Scientific registry data from 1990 to 1996 was performed. RESULTS: Liver grafts consisted of 2,636 whole grafts (WLG), 246 liver donor grafts (LDG), 89 split liver graft (SLG), and 438 reduced-size grafts (RSG). Although the number of pediatric transplants were unchanged between 1990 and 1996, segmental grafts made up an increasing proportion from 14.5% to 29.2%, and WLG decreased proportionately. The increase among segmental grafts occurred for LDG (threefold), followed by SLG (53%) and RSG (50%). One-year graft and patient survival rates for 3,409 transplants were 69.7% and 81.9%, respectively and were significantly higher (P<.001) in nonhospitalized patients than in hospitalized patients (79.8% and 91.3% v 61.0% and 73.7%). LDG graft survival (75.9%) was comparable with WLG(70.9%) but significantly better at 1 year than SLG (60.3%, P = .007) and RSG (61.1%, P = .001), even after excluding retransplants and ICU patients. Patient survival rates were not different statistically between groups. A separate analysis of outcomes in recipients less than 1 year of age suggested significantly better graft and patient survivals for LDG (83.3% and 89.4%) than for WLG (62.3% and 76.5%) and RSG (62.7% and 75%). CONCLUSIONS: Segmental liver grafts from cadaveric and living donors constitute an increasing proportion of pediatric transplants. Survival rates of cadaveric segmental graft are inferior to those of live donor segmental grafts even after adjustment for medical condition. Live donor grafts demonstrate consistently superior graft and patient outcomes in pediatric recipients less than 1 year of age, and should be promoted aggressively as a solution to the critical shortage of size matched grafts in small recipients.