RESUMEN
UNLABELLED: A perfect or nearly perfect human leukocyte antigen (HLA) match has been associated with better immediate and long-term survival of diseased donor kidney transplants. However, the effect of HLA matching for hepatic allografts remains poorly defined. Using data from the National Institutes of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, we investigated the association between HLA mismatches and hepatic allograft survival, disease recurrence, and immunosuppression interactions. A, B, and DR loci were used to calculate total mismatch scores of 0 (no mismatches in any loci) to 6 (mismatches in all loci). Seven hundred ninety-nine adults (male, 55%; female, 45%) underwent 883 liver transplants. The 10-year graft survival according to total mismatch score was as follows: 0-2, 60%; 3-4, 54%; and 5-6, 57%. There was a negative effect of mismatching at the A locus on patient survival, with shorter survival for patients with 1 or 2 mismatches compared with 0 mismatches [P = 0.05, hazard ratio (HR) = 1.6]. Patients on tacrolimus with 1 or 2 mismatches at B or DR loci appeared to have increased rates of patient and graft survival compared to patients with 0 mismatches, with the appearance of a protective effect of tacrolimus (HR = 0.67). The effect of HLA mismatching was more pronounced on certain disease recurrences. DR-locus mismatch increased recurrence of autoimmune hepatitis (P = 0.01, HR = 4.2) and primary biliary cirrhosis (P = 0.04, HR = 2). Mismatch in the A locus was associated with more recurrence of hepatitis C virus (P = 0.01, HR = 1.6) and primary sclerosing cholangitis (P = 0.03, HR = 2.9). CONCLUSION: Mismatching at the A locus decreases patient survival in liver transplant recipients, and mismatching at the DR and A loci affects recurrence of autoimmune liver diseases and hepatitis C, respectively.
Asunto(s)
Bases de Datos como Asunto , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Hígado/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Antígenos HLA-A/inmunología , Antígenos HLA-DR/inmunología , Hepatitis C/inmunología , Hepatitis C/cirugía , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/cirugía , Humanos , Inmunosupresores/uso terapéutico , Cirrosis Hepática Biliar/inmunología , Cirrosis Hepática Biliar/cirugía , Estudios Longitudinales , Masculino , Persona de Mediana Edad , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)/estadística & datos numéricos , Tacrolimus/uso terapéutico , Resultado del Tratamiento , Estados UnidosRESUMEN
Improving a patient's quality-of-life (QOL) post-liver transplantation is of great importance. An aspect of improved QOL is the restoration of normal growth patterns in pediatric patients. To describe the post-transplantation growth patterns of 72 children included in the National Institute of Diabetes and Digestive and Kidney Diseases - Liver Transplantation Database (NIDDK-LTD), multilevel models were used, according to which children who waited more than a year for transplantation were smaller, compared with age and sex matched peers, at transplantation than children who waited less than a year while children who were growth retarded at transplantation experienced a larger yearly comparison height increase than children who were not growth retarded. The analysis also showed that boys older than 2 yr and younger than 13 yr at transplantation and girls older than 2 yr and younger than 11 yr at transplantation were significantly less growth retarded at transplantation than boys and girls under the age of 2 yr at transplantation.
Asunto(s)
Desarrollo Infantil , Trastornos del Crecimiento/etiología , Trasplante de Hígado , Adolescente , Estatura , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Trastornos del Crecimiento/fisiopatología , Humanos , Terapia de Inmunosupresión , Lactante , Trasplante de Hígado/efectos adversos , Masculino , Estudios Prospectivos , Calidad de Vida , Factores de Riesgo , Estadísticas no Paramétricas , Listas de EsperaRESUMEN
BK virus (BKV) nephropathy is a serious complication in kidney transplant recipients that may lead to irreversible graft failure. We have analyzed the degree of donor/recipient HLA compatibility and HLA antigen association in 40 kidney transplant patients with BKV nephropathy in comparison with a control group of 404 unaffected transplant recipients who were on tacrolimus-based immunosuppression with no induction. HLA compatibility was assessed by determining the number of HLA-A, -B, -DR-mismatched antigens. BK virus nephropathy was diagnosed histologically and confirmed by immunochemistry. Univariate and multiple logistic regression statistical analyses have shown a significant association between BKV nephropathy and HLA mismatching. This analysis showed also that BKV nephritis is associated with a greater number of rejection episodes and a higher incidence of steroid-resistant rejection requiring antilymphocyte treatment. There was no association between BKV nephropathy and any specific HLA allele. We propose that HLA mismatching promotes the development of BKV nephropathy through rejection-related inflammatory processes and heavy immunosuppression which cause virus reactivation and injury of the tubular epithelium.
Asunto(s)
Virus BK/inmunología , Antígenos HLA/inmunología , Trasplante de Riñón , Riñón/virología , Infecciones por Polyomavirus/inmunología , Infecciones Tumorales por Virus/inmunología , Adulto , Femenino , Humanos , Riñón/inmunología , Masculino , Persona de Mediana Edad , Tacrolimus/sangreRESUMEN
Hepatitis C virus (HCV)-associated liver disease is the most common indication for liver transplantation (LT). There are, however, no long-term (>5 year) studies of comparative outcomes for recipients with HCV infection, and no models capable of identifying recipients with HCV infection at greatest risk for adverse outcomes. We prospectively determined: 1) long-term outcomes, and 2) whether pretransplant patient or donor variables can be used to predict death and/or graft loss in recipients with HCV infection. A total of 165 HCV-infected recipients were eligible for this study. Pretransplant donor and recipient characteristics and patient and graft survival data were prospectively collected. Model building for outcomes was carried out using logistic regression. Receiver operating characteristic curves for different models were created and compared. Median follow-up was 8.5 years. Adjusted 10 year graft survival was 64% for recipients with HCV infection and 51% for uninfected recipients. A model incorporating pretransplant HCV ribonucleic acid (RNA), cytomegalovirus immunoglobulin (CMV IgG) serostatus, creatinine, bilirubin, prothrombin time international ratio (INR), recipient age, and donor age was developed to identify recipients at greatest risk of short-term mortality or graft loss (area under receiver operating characteristic curve = .83) In conclusion, long-term outcomes following LT for recipients with HCV infection are comparable to those for recipients undergoing LT for other indications. HCV-infected recipients at greatest risk for short-term mortality and graft loss can be identified using several readily identifiable pretransplant variables. Long-term death and graft loss specifically secondary to recurrence of HCV appears, however, to be determined primarily by factors other than those included in this analysis.
Asunto(s)
Hepatitis C/cirugía , Trasplante de Hígado , Modelos Logísticos , Adulto , Femenino , Genotipo , Supervivencia de Injerto , Hepacivirus/genética , Hepatitis C/mortalidad , Humanos , Funciones de Verosimilitud , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Medición de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Interleukin-6 (IL-6) is a pleiotropic acute reactant cytokine involved in inflammatory responses. To explore the role of IL-6 in inflammation, this study examined the efficacy of exogenous IL-6 in preventing intestinal ischemia/reperfusion (I/R) injury associated with small bowel transplantation (SBTx). Syngenic orthotopic SBTx was performed in Lewis rats after 6-h graft preservation in University of Wisconsin (UW) at 4 degrees C. IL-6 mutein (IL-6m, 500 microg/kg), a recombinant molecular variant of human IL-6, was subcutaneously given to donors 2 h before harvesting (IL-6mD) or to excised grafts by luminal infusion (IL-6mG). Animal survival was 100% and 75% in IL-6mD (p<0.05 vs. control) and IL-6mG groups, respectively, compared with 64.3% in untreated controls. The severity of I/R injury (e.g. epithelial denudation, villous congestion) was reduced with IL-6m, in addition to a striking increase in re-epithelization. With IL-6m, neutrophil extravasation was markedly reduced in intestinal grafts and in remote organs (e.g. lung). IL-6m mediated anti-inflammatory effects through the inhibition of I/R-induced up-regulation of intragraft and circulating IL-1-beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. IL-6m also increased intestinal graft tissue blood flow. These results show that IL-6 is effective in protecting the intestine from cold I/R injury by maintaining graft blood flow and reducing pro-inflammatory cytokine up-regulation and neutrophil infiltration.
Asunto(s)
Inflamación/tratamiento farmacológico , Interleucina-6/fisiología , Intestinos/patología , Trasplante de Órganos/métodos , Daño por Reperfusión/prevención & control , Enfermedad Aguda , Animales , Benzotiazoles , Western Blotting , Citocinas/biosíntesis , Citocinas/metabolismo , Diaminas , Inmunohistoquímica , Interleucina-1/biosíntesis , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/irrigación sanguínea , Pulmón/metabolismo , Pulmón/patología , Masculino , Mutación , Neutrófilos/metabolismo , Compuestos Orgánicos/farmacología , Peroxidasa/metabolismo , Quinolinas , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Lew , Proteínas Represoras/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas , Factores de Tiempo , Factores de Transcripción/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis , Regulación hacia ArribaRESUMEN
One hundred and seventy-two patients underwent small bowel transplantation at Children's Hospital of Pittsburgh and University of Pittsburgh Medical Center between May 1990 and August 2001. Thirty-four patients had complete or partial resection of their primary graft and in 15, histologic features of chronic rejection were present in the resected small bowel. This is a descriptive and correlative study of the demographic, perioperative, and histologic features associated with progression to intestinal graft failure. Variable features associated with an increased risk of chronic rejection included acute rejection within the 1st month, increased number and higher grade of acute rejection episodes, isolated small bowel grafts rather than small bowel-liver grafts, older recipient age, non-Caucasian race, and Caucasian to non-Caucasian transplant. The mucosal biopsies showed predictive changes many months before the grafts were excised. The mucosal biopsy diagnosis of chronic vascular rejection can be difficult because the affected vessels, the distal branches of the mesenteric arteries, and the larger arteries of the subserosa and submucosa are not routinely sampled. The possibility of underlying arteriopathy, however, can be inferred in some instances from the presence of secondary mucosal changes in the small bowel biopsies though the "early" changes lack specificity. It is the progression of biopsy findings over time that is predictive of outcome. It is important to recognize the persistence of "late" mucosal changes of chronic rejection so that patients are not subjected to increased immune suppression when it is unlikely to be of significant benefit.