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1.
Pediatr Transplant ; 26(6): e14322, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35582739

RESUMEN

BACKGROUND: Vaccine preventable illnesses are important sources of morbidity, mortality, and increased healthcare costs in pediatric LT recipients. Our aim was to measure the seroprevalence of antibodies to measles and VZV in this population. METHODS: We conducted a retrospective chart review of 44 patients who received LT before age 18 at UCLA Mattel Children's Hospital from January 2008 to December 2017. RESULTS: Median age at transplantation was 2.5 years (IQR 1.2-7.7). Post-transplant measles antibodies were present in 17 of 37 patients (46%); risk factors for seronegativity included younger age at transplant (p = .02) and greater time from transplant to testing (p = .04). Post-transplant VZV antibodies were present in 17 of 39 patients (44%); risk factors for seronegativity included greater time from transplant to testing (p = .04). 6 of 16 patients (38%) who tested positive for pre-transplant VZV antibodies tested negative after transplantation. Fourteen of 20 patients (70%) with at least 1 documented dose of the MMR vaccine tested positive for post-transplant measles antibodies. Ten of 20 of patients (50%) with at least 1 documented dose of the VZV vaccine tested positive for post-transplant VZV antibodies. We also describe 10 patients who received post-transplant measles and VZV vaccines without documented complications. CONCLUSIONS: Our study suggests that pediatric LT patients are at greater risk of contracting measles and VZV despite vaccination status, and that prevalence of measles and VZV antibodies decreases as time from transplantation increases. This should weigh into the institutional risk-benefit assessment when deciding whether or not to administer LAVs to these patients.


Asunto(s)
Varicela , Trasplante de Hígado , Sarampión , Paperas , Adolescente , Anticuerpos Antivirales , Varicela/epidemiología , Varicela/etiología , Niño , Humanos , Sarampión/prevención & control , Paperas/prevención & control , Estudios Retrospectivos , Estudios Seroepidemiológicos
2.
Liver Transpl ; 28(10): 1640-1650, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35395132

RESUMEN

Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long-term outcomes and sustainability of tolerance have not been well studied. We completed a 10-year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed "stable" and "nontolerant" patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6-8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9-22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9-22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5-18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo ) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow-up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.


Asunto(s)
Trasplante de Hígado , Biomarcadores , Femenino , Rechazo de Injerto/prevención & control , Humanos , Tolerancia Inmunológica , Inmunosupresores/efectos adversos , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Masculino , Estudios Prospectivos , Tolerancia al Trasplante
3.
Liver Transpl ; 27(12): 1788-1798, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33977642

RESUMEN

Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post-LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long-term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux-en-Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range [IQR], 10.9-90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76-308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT [re-LT]) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long-term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long-term external catheter drainage until re-LT or percutaneous obliteration of isolated ducts.


Asunto(s)
Colestasis , Trasplante de Hígado , Niño , Preescolar , Colangiografía/métodos , Colestasis/etiología , Colestasis/cirugía , Constricción Patológica/etiología , Constricción Patológica/cirugía , Drenaje/métodos , Humanos , Lactante , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
4.
Transplantation ; 105(7): 1502-1509, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33208695

RESUMEN

BACKGROUND: T lymphocyte-mediated acute rejection is a significant complication following solid organ transplantation. Standard methods of monitoring for acute rejection rely on assessing histological tissue damage but do not define the immunopathogenesis. Additionally, current therapies for rejection broadly blunt cellular immunity, creating a high risk for opportunistic infections. There is, therefore, a need to better understand the process of acute cellular rejection to help develop improved prognostic tests and narrowly targeted therapies. METHODS: Through next-generation sequencing, we characterized and compared the clonal T-cell receptor (TCR) repertoires of graft-infiltrating lymphocytes (GILs) and blood-derived lymphocytes from a hand transplant recipient over 420 days following transplantation. We also tracked the TCR clonal persistence and V beta (BV) gene usage, evaluating overlap between these 2 compartments. RESULTS: TCR repertoires of blood and GIL populations remained distinct throughout the sampling period, and differential BV usage was consistently seen between these compartments. GIL TCR clones persisted over time and were seen in only limited frequency in the blood T-lymphocyte populations. CONCLUSIONS: We demonstrate that blood monitoring of TCR clones does not reveal the pathogenic process of acute cellular rejection in transplanted tissue. GILs show clonal persistence with biased BV usage, suggesting that tissue TCR clonal monitoring could be useful, although a deeper understanding is necessary to prognosticate rejection based on TCR clonal repertoires. Finally, the distinct TCR BV usage bias in GILs raises the possibility for prevention and therapy of acute cellular rejection based on targeting of specific TCR clones.


Asunto(s)
Genes Codificadores de los Receptores de Linfocitos T , Rechazo de Injerto/genética , Trasplante de Mano , Inmunidad Celular , Trasplante de Piel , Linfocitos T/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Supervivencia de Injerto , Mano , Trasplante de Mano/efectos adversos , Humanos , Fenómenos Inmunogenéticos , Masculino , Persona de Mediana Edad , Trasplante de Piel/efectos adversos , Linfocitos T/metabolismo , Factores de Tiempo , Resultado del Tratamiento
5.
Transplantation ; 104(12): 2547-2556, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32101982

RESUMEN

BACKGROUND: Angiotensin II type-1 receptor (AT1R) antibodies have been associated with rejection and allograft loss in solid organ transplantation and may act synergistically with HLA donor-specific antibodies (DSA). Our aims were to assess the prevalence of AT1R antibodies and determine if they were associated with allograft dysfunction in pediatric liver transplant recipients. METHODS: We performed a retrospective, cross-sectional study of HLA DSA and AT1R antibodies in 2 cohorts of pediatric liver transplant recipients: a stable control cohort with normal allograft function (n = 70) who consented to have serum samples collected for research purposes during a routine clinic visit and a cohort with active allograft dysfunction (n = 9) whose serum samples were collected as part of clinical care. RESULTS: AT1R antibodies >17 U/mL were detected in 29% of stable control patients and 89% of patients with active allograft dysfunction (P = 0.001). In stable control patients, AT1R antibodies were associated with younger age at transplant (P = 0.010), younger age at time of sample collection (P < 0.001), shorter interval since transplant (P = 0.090), and presence of HLA DSA (P = 0.003). AT1R antibodies in stable control patients were not associated with rejection or allograft loss. However, AT1R antibodies combined with HLA DSA in patients with active allograft dysfunction were associated with rejection and allograft loss. CONCLUSIONS: Our results suggest that AT1R antibodies are more common in patients with active allograft dysfunction and may be a risk factor for worse outcomes. Further research is needed to longitudinally assess the clinical impact of HLA DSA and AT1R antibodies.


Asunto(s)
Autoanticuerpos/sangre , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/inmunología , Receptor de Angiotensina Tipo 1/inmunología , Factores de Edad , Biomarcadores/sangre , Niño , Preescolar , Estudios Transversales , Femenino , Antígenos HLA/inmunología , Humanos , Lactante , Isoanticuerpos/sangre , Masculino , Complicaciones Posoperatorias/sangre , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
6.
SAGE Open Med ; 7: 2050312119866944, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31384465

RESUMEN

In this article, we present a report from a national meeting titled, "Evolving Issues of Vascularized Composite Allotransplantation-A Symposium on Ethics, Policy, and Reimbursement Issues," which convened in September 2017. We discuss the maturation of vascularized composite allotransplantation from an emerging technology to becoming an extension of clinical practice for select patients with complex reconstructive needs. Viewpoints and action items were presented by and discussed among the 70+ clinicians, researchers, policymakers, ethicists, healthcare administrators, and third-party payers who attended the symposium with the goals of implementing a collaborative roadmap for vascularized composite allotransplantation growth, evaluation, and sustainability by establishing a unified plan to help address concerns of the public, policymakers, and healthcare finance. We review the current status of vascularized composite allotransplantation in clinical practice and summarize symposium discussions regarding ethical considerations, reimbursement, payer strategies, and standardization of data collection.

7.
Pediatr Transplant ; 23(6): e13537, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31343109

RESUMEN

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.


Asunto(s)
Supervivencia de Injerto , Fallo Hepático/cirugía , Trasplante de Hígado , Adolescente , Aloinjertos , Niño , Preescolar , Accesibilidad a los Servicios de Salud , Humanos , Terapia de Inmunosupresión , Lactante , Cooperación del Paciente , Pediatría , Complicaciones Posoperatorias , Mejoramiento de la Calidad , Riesgo , Obtención de Tejidos y Órganos/métodos , Transición a la Atención de Adultos , Resultado del Tratamiento , Listas de Espera
8.
Am J Transplant ; 19(3): 865-875, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30091824

RESUMEN

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.


Asunto(s)
Aloinjertos Compuestos/trasplante , Supervivencia de Injerto , Complicaciones Posoperatorias , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/normas , Alotrasplante Compuesto Vascularizado/normas , Listas de Espera/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Estados Unidos , Adulto Joven
9.
Curr Opin Organ Transplant ; 23(5): 605-614, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30138149

RESUMEN

PURPOSE OF REVIEW: This review will focus on the lessons learned over several decades of solid organ transplantation in children, and their relevance to the emerging field of pediatric VCA. Particular attention will be focused on the risk-benefit ratio of immunosuppression as it applies to children receiving a life-enhancing transplant as compared with a life-saving transplant. Potential indications for pediatric VCA will be considered. RECENT FINDINGS: The report in 2015 of the first child to receive a VCA, bilateral upper extremity grafts from a nonrelated deceased donor, is a seminal event. The case is unique in that the child was already immunosuppressed after a prior kidney transplant. Early graft function is excellent and cortical re-organization has been described. SUMMARY: Although the risks of immunosuppression remain a formidable obstacle to the wider spread application of VCA for children, careful consideration of indications and outcomes for these innovative procedures, which have the potential to restore form and function not otherwise achievable, is warranted.


Asunto(s)
Terapia de Inmunosupresión/métodos , Trasplante de Órganos/métodos , Alotrasplante Compuesto Vascularizado/métodos , Niño , Humanos
10.
Plast Reconstr Surg ; 142(3): 405e-411e, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29927830

RESUMEN

Living donation has become a medically and ethically accepted practice in solid organ transplantation. Published proceedings from the international kidney transplant community and from the Ethics Committee of The Transplantation Society articulated the general principles and specific recommendations for living donation, which remain the backbone of Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network requirements and policies. Meanwhile, there have been major advancements in another revolutionary field of transplant medicine: vascularized composite allotransplantation. Recent interventions have demonstrated potential for superior functional and aesthetic outcomes in a single operation when compared to staged conventional reconstructions. In view of these successes, the indications for vascularized composite allotransplantation are expected to broaden to include less extensive types of transplants, which would introduce the possibility of using living vascularized composite allotransplantation donors. In this article, the authors discuss the feasibility and ethics associated with living donation of vascularized composite allografts. The authors explore the current guidelines and policies set by the Organ Procurement and Transplantation Network regarding living organ donation. In addition, the authors provide several clinical scenarios in which living donation of vascularized composite allotransplantation could be used to augment the reconstructive ladder currently used by reconstructive surgeons to guide their reconstructive strategies.


Asunto(s)
Aloinjertos Compuestos/trasplante , Donadores Vivos , Obtención de Tejidos y Órganos/normas , Alotrasplante Compuesto Vascularizado/normas , Humanos , Guías de Práctica Clínica como Asunto , Obtención de Tejidos y Órganos/ética , Alotrasplante Compuesto Vascularizado/ética , Alotrasplante Compuesto Vascularizado/métodos
11.
Clin Transplant ; 32(8): e13313, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29888807

RESUMEN

Post-transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single-center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy-proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow-up time of 6.4 (1.6-14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re-ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999.


Asunto(s)
Intestinos/trasplante , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/patología , Complicaciones Posoperatorias/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Trastornos Linfoproliferativos/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
12.
J Am Coll Surg ; 226(4): 355-366, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29410290

RESUMEN

BACKGROUND: Pediatric liver transplantation (pLTx) has been the standard of care for children with liver failure since the 1980s. This study examined the world's largest single-center experience and aimed to identify unique preoperative predictors of early graft and patient survival for primary transplantation (1°-pLTx) and retransplantation (Re-pLTx). STUDY DESIGN: We conducted an IRB-approved, retrospective study of all consecutive, isolated pLTx patients 18 years of age or younger. Twenty-eight demographic, laboratory, and perioperative variables were analyzed as potential outcome predictors. Univariate and multivariate analyses were performed using log-rank test and Cox's proportional hazards model. RESULTS: There were 806 children who received 1,016 isolated pLTx between February1984 and June 2017. Median follow-up was 12 years. Leading indications for pLTx were cholestatic liver disease (40%), re-pLTx (21%), and fulminant hepatic failure (14%). Seventy-three percent received cadaveric whole grafts. Overall graft and patient survival rates at 0.5, 1, 5, 10, and 20 years were: 76%, 73%, 67%, 63%, 53%, and 87%, 86%, 81%, 78%, 69%, respectively. Relative to 1°-pLTx, re-pLTx recipients were significantly older, larger, with worse renal function, and more likely to be awaiting pLTx in an ICU. Independent significant predictors of graft survival for 1°-pLTx included weight, transplantation era, and renal replacement therapy; for re-pLTx, warm ischemia time and time between 1°-pLTx and re-pLTx. Independent significant predictors of patient survival were renal function, mechanical ventilation, and etiology of liver disease. CONCLUSIONS: This is the largest reported single-center experience of pLTx with substantial follow-up time and a large re-pLTx experience. Important transplant predictors of graft survival include weight, renal function, modern era, warm ischemia time, and time between primary transplantation and re-pLTx. Renal function, mechanical ventilation, and underlying cause of liver disease affect patient survival. Awareness of these factors can help in the decision making for children requiring pLTx.


Asunto(s)
Fallo Hepático/cirugía , Trasplante de Hígado , Adolescente , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Lactante , Fallo Hepático/diagnóstico , Fallo Hepático/mortalidad , Masculino , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
13.
Pediatr Transplant ; 22(2)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29363222

RESUMEN

The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging field of study. Although OPV has previously been described as a histopathologic finding in DSA-positive adult LT recipients, it was not included in the recent Banff criteria for chronic AMR. Our aim was to describe the association between OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67 liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT recipients identified four patients with OPV. Clinical status, liver biochemistry, the presence of DSA, and available non-HLA antibody testing, as well as histopathologic features of chronic AMR, were assessed. All four patients with OPV had class II DSA and histopathologic features of chronic AMR based on the Banff criteria. Two patients were noted to have non-HLA antibodies. Three patients are undergoing treatment with IVIG but have persistent DSA. Two patients have graft failure and are awaiting retransplantation. In conclusion, OPV is a histopathologic finding associated with chronic AMR in pediatric LT recipients. Further studies are needed to elucidate whether OPV is reversible and/or amenable to medical therapy.


Asunto(s)
Aloinjertos/patología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/patología , Trasplante de Hígado , Hígado/patología , Vena Porta/patología , Aloinjertos/inmunología , Biopsia , Niño , Preescolar , Enfermedad Crónica , Femenino , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Isoanticuerpos/inmunología , Hígado/inmunología , Masculino
14.
Pediatr Blood Cancer ; 64(12)2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28643391

RESUMEN

Although checkpoint inhibitor therapies have demonstrated significant efficacy in many malignancies, they have not been well studied in patients with a history of solid organ transplant. We describe two patients with recurrent, refractory, and progressive advanced fibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation who received programmed cell death protein 1 (PD-1) inhibitor, nivolumab, on a patient access, off-label basis. Both rapidly developed irreversible acute liver rejection shortly after starting therapy, and ultimately died. While checkpoint inhibitors clearly have tremendous potential as a targeted therapy, they should be avoided or used with extreme caution in the context of an organ transplant.


Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/terapia , Rechazo de Injerto/inducido químicamente , Neoplasias Hepáticas/terapia , Trasplante de Hígado/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adolescente , Adulto , Carcinoma Hepatocelular/patología , Resultado Fatal , Humanos , Neoplasias Hepáticas/patología , Masculino , Metástasis de la Neoplasia , Nivolumab
15.
Pediatr Transplant ; 21(1)2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27597379

RESUMEN

Acute AMR is well reported following ABO-incompatible LTx. However, it remains uncommon in ABO-compatible LTx. It typically presents with graft dysfunction ≤2 weeks post-LTx and is often associated with graft loss. We report the clinical presentation, treatment regimen, and outcome of six pediatric LTx recipients diagnosed with early acute AMR based on (i) clinical signs of graft dysfunction, (ii) histopathology indicative of acute injury ± C4d staining, and (iii) presence of HLA DSA. All patients developed elevated ALT and GGT ≤ 45 days post-LTx. All showed HLA class I (n=4) and/or II (n=6) DSA (peak MFI 6153-11 910). Four had de novo DSA, and two had preformed DSA. Five were initially diagnosed with ACR refractory to steroid therapy. Four exhibited resolution of graft dysfunction with AMR therapy. Two had refractory AMR-one was re-transplanted; the other was treated with eculizumab and showed improvement in graft function but later died due to a tracheostomy complication. Our case series suggests that AMR following ABO-compatible LTx may be under-diagnosed. The presentation can be variable, and treatment should be individualized. Eculizumab may be an option for refractory AMR. Ultimately, future multicenter studies are needed to better define diagnostic criteria, characterize optimal treatment, and assess long-term outcomes following liver AMR.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Anticuerpos/inmunología , Rechazo de Injerto/inmunología , Trasplante de Hígado , Anticuerpos Monoclonales Humanizados/uso terapéutico , Niño , Preescolar , Femenino , Supervivencia de Injerto , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Lactante , Isoanticuerpos/inmunología , Masculino , Estudios Retrospectivos , Donantes de Tejidos , Resultado del Tratamiento
16.
Transplantation ; 99(7): 1416-22, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26038872

RESUMEN

BACKGROUND: The role of donor-specific HLA antibodies (DSA) after pediatric liver transplantation (LTx) is not clearly established. We completed a cross-sectional study to characterize DSA in long-term survivors of pediatric LTx and assess the impact of C1q-binding DSA on allograft outcomes. METHODS: Serum samples were collected at routine clinic visits from 50 pediatric LTx recipients classified into 3 clinical phenotypes: nontolerant (n = 18) with de novo autoimmune hepatitis (DAIH) and/or late acute cellular rejection (ACR); stable (n = 25) on maintenance tacrolimus; operationally tolerant (n = 7). Samples were blinded, and antibody detection was performed using Luminex single antigen class I and II beads. Patients with positive DSA were tested for C1q-binding DSA. RESULTS: DSA were detected in 54% (n = 27) of the patients, with the majority directed at HLA class II antigens (DR, 41%; DQ, 53%). Patients with DSA were younger at the time of LTx (P = 0.016) and time of study (P = 0.024). Mean aspartate aminotransferase, alanine aminotransferase, total bilirubin, and gamma glutamyl transferase were higher in DSA-positive patients, though did not reach statistical significance. Nontolerant patients were significantly more likely to have DQ DSA (61%) compared to stable (20%) and tolerant (29%) patients (P = 0.021). The nontolerant phenotype was associated with DSA and C1q-binding DSA, with odds ratios of 13 (P = 0.015) and 8.6 (P = 0.006), respectively. The presence of DQ DSA was associated with DAIH and late ACR, with odds ratios of 12.5 (P = 0.004) and 10.8 (P = 0.006), respectively. CONCLUSIONS: Allograft dysfunction is not always evident in patients with DSA, but DQ DSA are strongly associated with DAIH, late ACR, and chronic rejection.


Asunto(s)
Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Hepatitis Autoinmune/inmunología , Histocompatibilidad , Isoanticuerpos/sangre , Trasplante de Hígado/efectos adversos , Tolerancia al Trasplante , Enfermedad Aguda , Adolescente , Factores de Edad , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Niño , Preescolar , Enfermedad Crónica , Complemento C1q/inmunología , Estudios Transversales , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Antígenos HLA-DQ/inmunología , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/prevención & control , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Factores de Riesgo , Tacrolimus/uso terapéutico , Factores de Tiempo , Tolerancia al Trasplante/efectos de los fármacos , Resultado del Tratamiento , Adulto Joven
17.
J Pediatr Gastroenterol Nutr ; 61(6): 636-40, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26020374

RESUMEN

OBJECTIVES: Biopsies remain the criterion standard in the diagnosis of intestinal transplant (ITx) rejection, and gastrointestinal endoscopy plays a pivotal role in patient management. Herein, we describe a single-center 23-year endoscopic experience in pediatric ITx recipients. METHODS: A retrospective review of endoscopy and pathology reports of all ITx recipients <18 years old transplanted between 1991 and 2013 was performed with the aim of describing the procedural indications, findings, and complications. RESULTS: A total of 1770 endoscopic procedures within 1014 sessions were performed. A combination of esophagogastroduodenoscopy and ileoscopy was the most common procedure (36%). Increased stool output (35%) and surveillance endoscopy (32%) were the most common indications. A total of 162 episodes of biopsy-proven rejection were diagnosed. The first episode of rejection occurred at a median of 1 month after ITx. Of histology-proven rejections, 45% had normal-appearing endoscopies. The rate of procedural complications, including but not limited to bleeding and perforation, was 1.8%. CONCLUSIONS: Endoscopy with biopsy plays a significant role in the care of ITx recipients. Multiple procedures are required for graft surveillance, diagnosis of rejection, subsequent treatment, and follow-up of therapy. The gross endoscopic appearance, particularly in mild to moderate acute cellular rejection, does not correlate well with histology. Complex anatomy, complication rates that are higher than patients with non-ITx pediatric endoscopy, and timely histologic interpretation by experienced pathologists are reasons that these procedures should be performed at centers accustomed to caring for ITx recipients. The field would benefit from the development of a noninvasive biomarker to reliably and efficiently detect rejection.


Asunto(s)
Endoscopía Gastrointestinal/métodos , Rechazo de Injerto , Intestinos/cirugía , Trasplante de Órganos , Adolescente , Biopsia , Niño , Preescolar , Femenino , Humanos , Lactante , Intestinos/patología , Masculino , Estudios Retrospectivos
18.
JAMA Surg ; 149(1): 77-82, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24257966

RESUMEN

IMPORTANCE: While orthotopic liver transplantation (OLT) is a durable life-saving treatment for patients with irreversible liver disease, the waiting list mortality rate for children younger than 6 years is 4 times higher than for children aged 11 to 17 years and adults owing to scarce availability of size-appropriate grafts for transplantation. OBJECTIVE: To compare long-term outcomes for children (aged ≤18 years) undergoing OLT using grafts from donation after circulatory death (DCD) and donation after brain death (DBD). DESIGN, SETTING, AND PARTICIPANTS: Retrospective study using case-control matched groups at a university transplant center. All patients aged 18 years and younger who underwent OLT using DCD organs between February 1, 1990, and November 30, 2010, at the University of California, Los Angeles, were matched in a 1 to 3 ratio with patients who received primary OLT from DBD donors within a 12-month period. Other matching criteria included recipient age, weight, cause of liver disease, and acuity of illness. Outcomes after OLT were compared for DCD (n = 7) and DBD (n = 21) donors. The median follow-up was 4.5 years. MAIN OUTCOMES AND MEASURES: The primary outcome measure was graft failure-free survival; the secondary end point was the development of ischemic cholangiopathy. RESULTS: Comparing DCD and DBD groups, recipient median age (28.4 vs 20.1 months, respectively; P = .80), weight (12.0 vs 11.6 kg, respectively; P = .87), Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score (19 vs 11, respectively; P = .48), and donor age (24.0 vs 13.1 months, respectively; P = .72) were similar. For the DCD donors, the median donor warm ischemia duration was 24 minutes. Liver test results were similar for both groups at 1 week and 3, 6, and 12 months following OLT. Ten-year patient and graft survival rates for both DCD and DBD were 100%. Neither ischemic cholangiopathy nor vascular complications occurred in the DCD group. Biliary anastomotic strictures occurred in 1 DCD patient and 3 DBD patients. CONCLUSIONS AND RELEVANCE: Our study showed excellent long-term outcomes with liver transplantation in children using DCD organs. Use of liver grafts procured after circulatory death is an effective approach to expand the donor pool and remains an untapped resource for children with end-stage liver disease.


Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Estudios de Casos y Controles , Preescolar , Muerte , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
19.
Curr Opin Organ Transplant ; 18(6): 665-71, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24220049

RESUMEN

PURPOSE OF REVIEW: To understand the unique requirements of vascularized composite allograft (VCA) donation and procurement practices and the integral role of the established nationwide organ procurement organizations in organ procurement. RECENT FINDINGS: The recent issuance of a Final Rule (July 2013) by the United States Secretary of Health that redefines VCAs as organs rather than tissues, opens up the potential to formalize policies and procedures, under the auspices of the Organ Procurement and Transplantation Network, that can improve VCA donation, procurement practices, develop allocation algorithms and provide transparent oversight. SUMMARY: Improved VCA donation rates, procurement procedures and broader sharing nationwide of VCA donors will have important implications in advancing the emerging field of VCA transplantation.


Asunto(s)
Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos , Alotrasplante Compuesto Vascularizado/legislación & jurisprudencia , Aloinjertos/provisión & distribución , Humanos , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/organización & administración , Obtención de Tejidos y Órganos/normas , Estados Unidos
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