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Pre-transplant soluble CD30 is associated with bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: The purpose of this study was to determine the clinical relevance of soluble CD30 (sCD30) concentrations in sera from lung transplantation (LTx) candidates. METHODS: Soluble CD30 concentrations were determined by enzyme-linked immunoassay in pre-transplantation sera of 38 LTx candidates and in serial samples taken after LTx from 10 patients. RESULTS: LTx candidates did not have increased serum sCD30 concentrations when compared with healthy controls (mean +/- SE: 22.3 +/- 2.7 vs 26.2 +/- 3.4 U/ml). No relation could be found between age and serum sCD30 concentrations, neither in the pre-transplant patients nor in the healthy controls. In addition, no differences in sCD30 values could be detected between patients sorted by their original type of lung disease. Measurement of sCD30 in pre-transplant sera of LTx patients showed that the median concentration was 20 U/ml and that LTx patients with low sCD30 (< or = 20 U/ml) had a statistically significant (p = 0.039) longer period of freedom from bronchiolitis obliterans syndrome (BOS) compared to those with a high sCD30 concentration (> 20 U/ml). Furthermore, sCD30 concentrations in sera taken at several timepoints after LTx remained stable, although a peak could be observed before the clinical manifestation of acute rejection (AR). CONCLUSIONS: Soluble CD30 before lung transplantation is significantly associated with an increased risk of BOS after transplantation.

Biomarkers↗

Oxidative stress and post-transplant hypertension in pediatric kidney-transplanted patients.

OBJECTIVE: To test the hypothesis that oxidative stress signaling contributes to post-transplant endothelial dysfunction and hypertension in pediatric post-transplant hypertension. STUDY DESIGN: This study evaluated in 16 pediatric renal transplant patients, divided in two groups based on the presence of post-transplant hypertension, the oxidative stress status measuring the gene expression (reverse transcription-polymerase chain reaction) of two major oxidative stress-related proteins, p22(phox) and heme oxygenase-1 (HO-1). Total plasma antioxidant power (ELISA) was also evaluated. RESULTS: Mononuclear cell p22(phox) gene expression was higher in hypertensive patients compared with the normotensive group (0.91 +/- 0.06 vs 0.79 +/- 0.08 densitometric units, P < .02), whereas HO-1 RNA production and total plasma antioxidant power were higher in the normotensive group (0.38 +/- 0.04 vs 0.20 +/- 0.11 d.u., P < .006, and 1189.35 +/- 145.75 vs 772.71 +/- 196.03 micromol/L, P < .01, respectively). CONCLUSIONS: Oxidative stress is associated with post-transplant hypertension in hypertensive pediatric kidney-transplant patients, who therefore are at risk of oxidative stress-induced organ damage. They might benefit from treatments addressing not only hypertension but also oxidant-related complications.

Adolescent↗

Skin cancer following transplantation: the Israel Penn International Transplant Tumor Registry experience.

UNLABELLED: The purpose of this study was to analyze a large series of skin cancers in solid organ transplant recipients to determine their biologic behavior. METHODS: A retrospective review of all US transplant recipients with skin cancer reported to the Israel Penn International Transplant Tumor Registry was performed. RESULTS: Transplant recipients from the United States with skin malignancies were identified (n = 2018) and assigned to 1 of 3 groups: squamous cell cancer (SCC), basal cell cancer (BCC), or combined malignancies (BCC/SCC). Squamous cell to basal cell cancer ratio was found to be 1.9 to 1. The ratio of extrarenal to renal allograft recipients was identical for all 3 groups (3:1). The median interval from transplant to skin cancer diagnosis was greater than 4 years in each group and longest in those with isolated SCC lesions. In the SCC group, there was a 9% incidence of nodal or secondary site involvement affecting the cervix, perineum, or lung. The highest recurrence rate was demonstrated in the combined malignancy group. Cancer-specific deaths were significantly higher in the SCC (8%) and BCC/SCC (6.8%) groups compared to the BCC (3.6%) group. CONCLUSIONS: This large experience indicates that SCC is more common than BCC in transplant recipients. SCC alone or in combination with BCC appears aggressive and is associated with significant mortality.

Carcinoma, Squamous Cell↗

Living related liver transplantation. Why this option has been discarded in a pediatric liver transplant program in Chile.

Living related living transplantation (LRLT) has opened new possibilities for planning transplantation in better conditions for children with emergency situations and chronic liver diseases. Since we began the LRLT program in 1999, we have performed 57 pediatric liver transplants, 17 (29.8%) using living related donors (LRD). The aim of this study was to analyze the reasons why LRD were discarded as a therapeutic option. All pediatric patients were prospectively included in our Microsoft Excel database that was reviewed for obtaining information about causes why the LRLT could not be done. LRLT was proposed in 28 cases and performed in 17 (60.7%). The reasons for LRD rejection were: parent's fear of surgical complications in four cases; drug abuse in two; a mother without family support; medical reasons in two; and only one, due to anatomical reasons and in one case, cadaveric graft transplantation was performed while completing the father's evaluation. From these eleven cases, the indications for liver transplant were acute liver failure (ALF) in seven, biliary atresia in three, and Alagille syndrome in one. Nine were transplanted with cadaveric organs, but two patients with ALF died awaiting a liver. Efforts should be made to clarify the advantages and the disadvantages of LRD in each case, allowing parents to make a free, well-informed decision.

Attitude to Health↗

The paradox of survival results after heart transplantation for cardiomyopathy caused by Trypanosoma cruzi. First Guidelines Group for Heart Transplantation of the Brazilian Society of Cardiology.

BACKGROUND: Donor supply limits heart transplantation (HT) and relative priority should be given to cases with greater chances of success. The objectives of this multicenter study were (1) to determine the survival rate after heart transplantation for patients with Chagas' heart disease (ChHD) in comparison with other causes; and (2) to identify the causes of death specifically due to reactivation of the Trypanosoma cruzi infection. METHODS: We studied 720 patients who had undergone orthotopic heart transplantation and were followed in 16 heart transplantation centers. The etiology was idiopathic dilated cardiomyopathy in 407 patients, ischemic cardiomyopathy in 196 patients, and ChHD in 117 patients. RESULTS: Follow-up was 2.87 +/- 3.05 years (from 1 month to 13.85 years). Survival of ischemic recipients at 1, 4, 8, and 12 years was 59%, 44%, 34%, and 22%, respectively; for idiopathic dilated cardiomyopathy it was 69%, 57%, 40%, and 32%; and for ChHD it was 71%, 57%, 55%, and 46% (p < 0.027). In ischemic recipients the most frequent causes of death were infection (15.3%), acute graft failure (13.3%), and graft coronary artery disease/sudden death (7.7%). In idiopathic dilated cardiomyopathy the causes were infection (11.1%), rejection (9.6%), and acute graft failure (9.1%). In ChHD the causes were infection (10.3%), rejection (10.3%), and neoplasm (4.3%). In ChHD, reactivation of the cruzi infection was the cause of death in 2 patients. CONCLUSIONS: The survival results after heart transplantation are paradoxical according to the usually high expected death rates for Chagas' disease. Heart transplantation for ChHD should be regarded as a valuable treatment option.

Adult↗

Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia.

The linear growth of 26 children with progressive and advanced neuroblastoma treated with high-dose chemotherapy, total body irradiation, and bone marrow transplantation between 1978 and 1988 at the Children's Hospital of Philadelphia was compared with the growth of 33 children who had transplants for leukemia and of 12 who had transplants for aplastic anemia. The mean growth velocity, expressed as a standard deviation score, for the children who underwent bone marrow transplantation for neuroblastoma was -2.83. This was significantly (p less than 0.005) less than the standard deviation scores for children with transplants for acute lymphoblastic leukemia, acute nonlymphocytic leukemia, and aplastic anemia, which were -0.98, -0.07, and -1.05, respectively. A 6-year follow-up study of 32 long-term survivors of cancer revealed that the 11 patients with neuroblastoma continued to grow poorly, whereas a comparison group of 21 survivors of bone marrow transplantation for leukemia had essentially normal growth 2 years after the procedure. Major therapeutic differences between the two groups included the doses of local radiotherapy and the type and number of cytotoxic agents used. In comparison with the relatively mild growth-inhibiting effects of preparative regimens for leukemia and aplastic anemia, the very intensive preparative regimens used in patients with neuroblastoma have significant negative effects on growth.

Anemia, Aplastic↗

Factors predictive of sustained growth in children after renal transplantation. The North American Pediatric Renal Transplant Cooperative Study.

To ascertain growth and rehabilitation of children after transplantation, the North American Pediatric Renal Transplant Cooperative Study collected growth data on renal transplant recipients. From January 1987 through December 1990, a total of 1553 children with one or more transplants were entered into the study by its 75 participating centers. Of these, the first 300 children with a functioning graft and 2 years of linear growth data form the cohort for this study. For the total cohort of 300 patients, the mean (+/- SEM) baseline height z score was -2.41 +/- 0.09, and the change in z score determined after 2 years was 0.18 +/- 0.06 (p < 0.01). Children in the age group from birth to 1 year had the maximal deficit and had the maximal improvement in z score, gaining about 1 SD (p < 0.01). For the 2- to 5-year-old group, the change in z score was about 0.5 SD (p < 0.001). No improvement in z score was noted for children 6 to 17 years of age. Each increase in serum creatinine concentration of 90 mumol/L (1 mg/dl) was associated with -0.17 decrease in the z score (p < 0.001). Gender, donor source, history of previous transplantation, and prior dialysis were not associated with a significant change in the z score; thus the increased rate of growth during the first 2 post-transplantation years occurred mainly in subjects less than 6 years of age.

Adolescent↗

Results of liver transplantation according to indications for orthotopic liver transplantation.

OBJECTIVE: This study assessed the results of liver transplantation in patients with a variety of different indications. METHODS: From 1989 to April 2003, 209 orthotopic liver transplantations (OLTx) were performed on 196 patients, including 178 cases. The diagnoses were: PBC (n = 34); PSC (n = 13); elective postinflammatory cirrhosis in the course of hepatitis C (n = 29); hepatitis B (n = 16); postalcoholic cirrhosis (n = 23), autoimmune cirrhosis (n = 11); Wilson's disease (n = 6); cirrhosis of unknown etiology (n = 10); secondary biliary cirrhosis (n = 5); Budd-Chiari syndrome (n = 6); and benign liver neoplasms (n = 7). RESULTS: The 3-year survival rate in the group of patients transplanted electively was 74.1%. In other groups it was: PBC, 91.4%; PSC, 69.2%; hepatitis C, 69.6%; hepatitis B, 55.5%; postalcoholic cirrhosis, 80%; autoimmune cirrhosis, 81.8%; Wilson's disease, 57.1%; secondary biliary cirrhosis, 40%; Budd-Chiari syndrome, 66.6%; hemochromatosis, 100%; benign neoplasms of the liver, 87.5%; and liver cysts, 100%. CONCLUSIONS: Results of liver transplantation were closely related to the urgency of the procedure. Better results were achieved in patients operated upon routinely compared with in those operated upon emergently (74.1% vs 50%). The best results of liver transplantation were achieved in patients transplanted on a routine basis with a diagnosis of PBC (91.4%), autoimmunologic cirrhosis (81.1%), postalcoholic cirrhosis (80%), or hemochoromatosis (100%). Patients with liver insufficiency due to hepatitis B and Wilson's disease have an increased risk of graft destruction, and the rate of survival in these patients is significantly lower than in other patients.

Female↗

Preoperative TNM-classification is a better prognostic indicator for recurrence of hepatocellular carcinoma after liver transplantation than albumin mRNA in peripheral blood. Liver Transplant Oncology Group.

BACKGROUND/AIM: Survival after orthotopic liver transplantation for hepatocellular carcinoma is limited by a high rate of tumor recurrence. A polymerase chain reaction assay based on the detection of albumin mRNA expression in peripheral blood for detection of hematogenous micrometastasis of hepatocellular carcinoma has been described, which may help to select candidates for orthotopic liver transplantation. METHODS: The prognostic value of a highly sensitive nested reverse transcription-polymerase chain reaction assay was evaluated in comparison with the TNM-classification of the International Union against Cancer in a population of liver transplant candidates. RESULTS: Eighty patients with liver disease and 42 control patients were evaluated. Six of 21 patients with hepatocellular carcinoma and 11 of 59 patients with other diseases of the liver were positive for albumin reverse transcription-polymerase chain reaction, making this assay an indicator of ongoing liver damage without absolute specificity for hepatocellular carcinoma. Twelve patients with hepatoma were followed after liver transplantation and seven of those patients had a tumor recurrence within 12 months. Six of these patients with recurrence had International Union against Cancer stage IV A tumors preoperatively, while only one of them was positive for albumin reverse transcription-polymerase chain reaction before transplantation. Only one patient with a stage I to III tumor had a recurrence within 12 months. CONCLUSIONS: Detection of albumin mRNA in peripheral blood by reverse transcription-polymerase chain reaction seems to be an unreliable marker for assessing hematogenous spread of hepatocellular carcinoma. With International Union against Cancer stage IV A being a much better predictor of tumor recurrence, the practical value of albumin mRNA reverse transcription-polymerase chain reaction for patient selection in liver transplant candidates seems to be very limited.

Adult↗

Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode.

BACKGROUND/AIMS: Antibodies to cytochrome P450 2D6, also known as LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C. METHODS: Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction. The serum of the organ donor was also tested. RESULTS: All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis C and G virus infection. DISCUSSION: We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.

Adult↗

Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy after cardiac transplantation.

Transplant associated coronary disease (TxCAD) is the main cause of late graft loss following cardiac transplantation. It is a multifactorial disease with immunologic and nonimmunologic components involved. This study was undertaken to analyze the gene polymorphism in adhesion molecules in donors and recipients and to investigate its potential association with the development of TxCAD. A total of 82 cardiac transplant patients, 96 donors and 101 UK controls, were genotyped retrospectively. Nine nucleotide polymorphisms in L-selectin, E-selectin, ICAM-1, and PECAM were analyzed using allele-specific PCR-SSP assay. Recipients were selected on the basis of the development of TxCAD: patients who had developed TxCAD within 2 years after transplantation, and patients who did not have TxCAD within 4.5-5 years after transplantation. All recipients received CyA and azathioprine as a primary immunosuppression. Associations were assessed by using Fisher's exact test. No association was found between E-selectin, L-selectin, and PECAM allele or genotype frequencies and TxCAD. However, the donors whose recipients did not develop TxCAD at first 2 years had a significant increase of ICAM-1 E-469 allele compared with donors, whose recipients developed TxCAD (63.8% vs 46.4%, p = 0.042) and to UK controls (63.8% vs 47%, p = 0.04). Moreover, we found that the decreased frequency of ICAM E469 allele was associated with the increased number of rejection episodes. The 469 E/K polymorphism is in exon 6 and results in a change from glutamic acid to lysine in Ig-like domain 5 of ICAM-1, which is thought to affect interactions with LFA-1 and adhesion of B-cells. Our data suggest the presence of allele E469 ICAM-1 in either donor or recipient is protective against allograft rejection in a transplant setting.

Coronary Disease↗

[Liver transplantation in the adult: who and when to transplant?].

INTRODUCTION: The shortage of cadaveric organ donors imposes a severe limit to the number of liver transplantations. A selection is thus necessary among patients: should the sickest be selected, or those who supposedly have the best chance to survive and recover? Optimizing the timing of transplantation during the course of the disease (not too early, but not too late) is another issue. CURRENT KNOWLEDGE AND KEY POINTS: Suitable candidates for transplantation are patients suffering from an irreversible, symptomatic liver disease. The goals of therapy are: firstly, to favorably modify the natural outcome of the disease; and secondly, in an acceptable risk taking manner. Major criteria for indication in the most common liver diseases can be summarized as follows: a) for chronic parenchymal liver diseases, a Child-Pugh score of 9 or 10, or less if complications have already occurred, is a mandatory and often sufficient criterion; b) for cholestatic liver diseases, a serum bilirubin level higher than 100-150 mumol/L is generally required; c) apart from "small" hepatocellular carcinomas on cirrhotic parenchyma (less than three tumors of less than 5 cm in diameter), most cancers are considered contraindications; d) acute liver failure requires early referral to a liver transplant center for potential emergency indication. FUTURE PROSPECTS AND PROJECTS: In an organ shortage situation which is likely to perdure, early consultative contact between the patient and the liver transplant team will allow improvement in the access to transplantation procedure.

Adult↗

[The results of the evaluation of 208 patients referred in the first 4 years to a lung transplantation program. The Lung Transplantation Group of Hospital Vall d'Hebron].

Retrospective analysis of the patients referred for possible lung transplants between 1990 and 1994. Between 1990 and 1994 the Lung Transplant Program at Hospital Vall d'Hebron received 208 referrals from all over Spain. The cases most often involved a combination of bronchiectasia and cystic fibrosis (29%), chronic obstructive pulmonary disease (25%) and pulmonary fibrosis (16.5%). Internationally established guidelines for lung transplantation were used to screen the cases and the results have been analyzed retrospectively. After first evaluating the report sent by the patient's pneumonologist, 100 patients (49%) were considered candidates for further hospital study. Of the 100, 53 (25%) were finally placed on an active waiting list. Twenty-seven (12.9%) of the 53 received transplants, 6 died while waiting, and the others remained on the waiting list on 31 December 1994. Mortality among the rejected patients between the first visit until the end of the study, excluding those who were not yet classified as serious cases and those who were terminally ill, was 36/123 (29%). Actuarial survival rates at 12 and 24 months for transplanted patients were 64 and 49%, respectively. After following the currently accepted screening methods, one in 4 patients referred for possible lung transplantation was finally given a place on the active waiting list. The series studied here is noteworthy for the relatively low number of patients with chronic obstructive pulmonary disease in comparison with other programs, although we expect the number to increase in the coming years.

Adolescent↗

Pulmonary transplantation for cystic fibrosis: pre-transplant recipient characteristics in patients dying of peri-operative sepsis.

BACKGROUND: Pulmonary transplantation has emerged as a successful treatment for end-stage cystic fibrosis. Despite the chronic bronchial sepsis and often multi-resistant organisms seen in this group of recipients, death due to post-operative sepsis is relatively scarce. Identifying potential recipient risk factors for poor outcome may further improve the utilization of a scarce donor pool. METHODS: We assessed the role of pre-operative clinical measures of sepsis, microbial characteristics and recipient characteristics on post-transplant outcome in 85 cystic fibrosis patients who underwent pulmonary transplantation. Ten percent of patients died in the early post-operative period due to sepsis. The prognostic role of recipient factors including markers of sepsis, such as white cells and C-reactive protein (CRP), and the influence of multi-resistant organisms, in particular organisms from the Burkholderia cepacia complex, on outcomes were investigated. RESULTS: We found no prognostic effect of gender, pre-transplant CRP, forced expiratory volume in 1 second (FEV(1)), weight, diabetic status or infection with multi-resistant Pseudomonas organisms. A raised white cell count or temperature or a pre-transplant infection with B cepacia was, however, associated with a significantly poorer prognosis at p = 0.03, 0.03 and 0.001, respectively. CONCLUSIONS: Pre-operative B cepacia complex infection, leukocytosis and pyrexia, but not CRP, weight, diabetes or lung function, were found to be associated with poorer post-transplant outcome. The most clinically relevant of these to the subsequent risk of post-operative death from sepsis appear to be B cepacia infection and pyrexia.

Biomarkers↗

Chronic transplant dysfunction and transplant arteriosclerosis: new insights into underlying mechanisms.

Although effective in the short-term, clinical solid-organ transplantation has not achieved its goals as a long-term treatment for patients with end-stage organ failure. Development of so-called chronic transplant dysfunction (CTD)is now recognised as the predominant cause of allograft loss long-term (after the first post-operative year) following transplantation. CTD has the remarkable histological feature that the luminal areas of intragraft arteries become obliterated, predominantly with vascular smooth muscle cells intermingled with some inflammatory cells. The development of this transplant vasculopathy,referred to as transplant arteriosclerosis (TA), is a multifactorial process and many risk factors have been identified. However, the precise pathogenetic mechanisms leading to TA are largely unknown and, as a result, current prevention and treatment protocols are inadequate. This review discusses the risk factors for TA and current views on the pathogenetic mechanisms leading to this vasculopathy. We argue here that host-derived cells contribute to the development of these vascular lesions, and propose that TA results from a normal vascular repair process that proceeds beyond the needs of functional repair. Guided by the proposed sequence of events, we finally discuss possible directions for future intervention strategies to prevent TA after solid-organ transplantation.

Arteriosclerosis↗

Pre-transplant identification of risk factors that adversely affect length of stay and charges for renal transplantation.

BACKGROUND: In the current era of renal transplantation, increasing attention is being focused on resource utilization. The purpose of this study was to identify demographic, medical and immunologic risk factors that are associated with changes in length of stay (LOS) and charges for renal transplantation. METHOD: The study was a retrospective analysis of 311 consecutive renal transplants performed at a single institution. Univariate and multivariate analyses were used to examine relationships between risk factors, LOS, charges and post-operative complications. RESULTS: The following pre-transplant variables were found to be independently significant in predicting increased LOS and/or charges: African-American race, obesity for women, chronic obstructive pulmonary disease (COPD), presence of cardiac disease or previous stroke, pre-transplant dialysis time > or = 1 yr, a 10% increase in panel reactive antibody (PRA), cadaver donor and retransplantation. The analyses were performed with and without adjustment for key outcome variables such as delayed graft function (DGF) and use of induction antibody therapy. Increased LOS or charges for specific risk factors could be attributed to increased complication rates, including delayed graft function seen with various co-morbidities, or increased immunologic risk and more frequent use of induction antibody therapy. CONCLUSION: Analysis of linked financial and clinical databases can reveal demographic, medical and immunologic risk factors that correlate with LOS, charges and complications for renal transplantation. Efforts to establish quantitative relationships for various risk factors relative to resource utilization will become important in managed care and/or capitated healthcare delivery systems.

Adult↗

The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), covering the years 1987-96 (January 15, 1997), analyzed data on 4898 patients who received 5362 transplants. Over the 10 yr of the study, 21.3% of the patients were under the age of 6 yr. Of the disorders that lead to end-stage renal disease (ESRD), structural and developmental anomalies of aplasia, dysplasia, and obstructive uropathy accounted for over 1500 patients. Despite the potential therapies for focal segmental glomerulosclerosis (FSGS), there has been little change in its incidence and this lesion continues to be the most common cause of renal failure and transplantation among acquired diseases. Eighty-nine per cent of patients with a functioning graft continue to receive cyclosporin A (CsA) 5 yr post-transplantation, and 84% of patients continue to receive azathioprine (AZA), whereas 26% of patients receive alternate-day steroid therapy at 4 yr post-transplant. Thirty-seven per cent of the living donor (LD) recipients and 47% of cadaver donor (CD) recipients were treated with the polyclonal T-cell antibody ATG/ALG for induction, and the monoclonal T-cell antibody, OKT3, was utilized for induction in 12% of LD patients and in 19% of CD patients. Twenty-five per cent of the 5362 transplants (1333) have failed over the 10-yr period. Graft survival is 90% at 1 yr and 74% at 6 yr for LD kidneys, and is 80% at 1 yr and 58% at 6 yr for CD patients. The most common cause for graft failure (30%) is chronic rejection. For recipients of LD grafts, relative risk (RR) factors for graft survival are African-American race (RR = 2.1, p < 0.001) and greater than five prior transfusions (RR = 1.6, p < 0.001). Prophylactic anti-T-cell antibody reduces the risk of graft failure (RR = 0.76, p = 0.009). For recipients of cadaver kidneys, risk factors are: recipient age < 2 yr (RR = 2, p < 0.001), donor age < 6 yr (RR = 1.3, p = 0.005), and absence of induction T-cell antibody (RR = 1.31, p < 0.001).

Adolescent↗

Characterization of hepatitis B virus surface antigen and polymerase mutations in liver transplant recipients pre- and post-transplant.

We evaluated serum samples from 18 chronic hepatitis B virus (HBV) patients who underwent liver transplantation for the presence of HBV polymerase and S gene mutations and HBV genotype using a new commercially available sequencing assay. All three patients with hepatitis B immune globulin (HBIG) treatment failure followed by nucleoside analogue treatment failure were infected with HBV genotype C; a pre-existing HBV S antigen (HBsAg) mutation (sD144A) was identified in one patient pretransplant, while sG145R mutations emerged in the other two patients post-transplant. These HBsAg mutations persisted for the duration of the study (5-6 years), despite the absence of HBIG administration for a 4-5-year period. Significant viral polymerase mutations (rtL180M and rtM204I/V) also emerged in all of these patients following treatment with lamivudine and/or famciclovir. Four of six patients with HBIG breakthrough without nucleoside analogue treatment failure yielded potentially significant HBsAg mutations post transplant. These data do not support previous reports highlighting the disappearance of HBsAg mutants in liver transplant recipients after discontinuation of HBIG. Determination of HBV genotype, as well as identification of HBV polymerase and S gene mutations in liver transplant candidates may be warranted to optimize HBV management strategies post transplant.

Chronic Disease↗