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1.
Pediatr Transplant ; 27 Suppl 1: e14283, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36468324

RESUMEN

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.


Asunto(s)
Hepatopatías , Trasplante de Hígado , Cirujanos , Obtención de Tejidos y Órganos , Niño , Humanos , Estados Unidos , Donantes de Tejidos , Listas de Espera
2.
Ann Surg ; 276(5): 846-853, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35894433

RESUMEN

OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Trasplante de Hígado , Benchmarking , Colangiocarcinoma/cirugía , Humanos , Tumor de Klatskin/patología , Tumor de Klatskin/cirugía , Nivel de Atención
3.
J Immunol ; 204(12): 3117-3128, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-32332110

RESUMEN

Defects in biliary transport proteins, MDR3 in humans and Mdr2 in mice, can lead to a spectrum of cholestatic liver disorders. Although B cell disorders and the aberrant Ab production are the leading extrahepatic manifestations of cholestatic liver diseases, the mechanism underlying this phenomenon is incompletely understood. Using mice with deficiency of Mdr2 that progressively develop cholestatic liver disease, we investigated the contributions of BAFF to aberrant IgG autoantibody production and hepatic fibrosis. In Mdr2-/- mice, hepatic B lymphocytes constitutively produced IgG during fibrosis progression, which correlated with elevated serum levels of BAFF, antinuclear Abs (ANA) and immune complexes. The elevated BAFF and ANA titers were also detected in human patients with primary sclerosing cholangitis and hepatobiliary cholangiopathies. Consistent with the higher BAFF levels, liver-specific selection of the focused BCR IgH repertoire was found on hepatic B cells in Mdr2-/- mice. Interestingly, the administration of anti-BAFF mAb in Mdr2-/- mice altered the BCR repertoire on hepatic B lymphocytes and resulted in reduced ANA and immune complex titers. However, anti-BAFF treatment did not attenuate hepatic fibrosis as measured by collagen deposition, hepatic expressions of collagen-1a, α-smooth muscle actin, and mononuclear cell infiltration (CD11b+ Ly-6chi monocytes and CD11b+ Gr1+ neutrophils). Importantly, depletion of B cells by anti-CD20 mAb reduced both hepatic fibrosis and serum levels of ANA and immune complexes. Our findings implicate B cells as the potential therapeutic targets for hepatic fibrosis and targeting BAFF specifically for attenuating the autoantibody production associated with cholestatic liver disease.


Asunto(s)
Factor Activador de Células B/inmunología , Colestasis/inmunología , Cirrosis Hepática/inmunología , Hígado/inmunología , Receptores de Antígenos de Linfocitos B/inmunología , Animales , Autoanticuerpos/inmunología , Fibrosis/inmunología , Células Estrelladas Hepáticas/inmunología , Humanos , Inmunoglobulina G/inmunología , Ratones
4.
Ann Surg ; 274(4): 613-620, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34506316

RESUMEN

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.


Asunto(s)
Antivirales/administración & dosificación , Carcinoma Hepatocelular/cirugía , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Anciano , Bencimidazoles/administración & dosificación , Carbamatos/administración & dosificación , Carcinoma Hepatocelular/virología , Esquema de Medicación , Combinación de Medicamentos , Femenino , Fluorenos/administración & dosificación , Hepatitis C Crónica/complicaciones , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Humanos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pirrolidinas/administración & dosificación , Quinoxalinas/administración & dosificación , Estudios Retrospectivos , Sofosbuvir/administración & dosificación , Sulfonamidas/administración & dosificación , Respuesta Virológica Sostenida
5.
J Pediatr ; 229: 78-85.e2, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32976893

RESUMEN

OBJECTIVE: To describe the assessment of Fontan-associated liver disease and determine the clinical and imaging measures that may identify hepatic morbidity risk in isolated heart transplantation candidates and trend those measures post-isolated heart transplantation. STUDY DESIGN: Retrospective analysis of pre-isolated heart transplantation and post-isolated heart transplantation Fontan-associated liver disease (FALD) status using blood tests, magnetic resonance imaging (MRI), and liver biopsy analysis within 6 months before isolated heart transplantation and 12 months after isolated heart transplantation in 9 consecutive patients with Fontan. Pre- and post-isolated heart transplantation standard laboratory values; varices, ascites, splenomegaly, thrombocytopenia (VAST) score; Fontan liver MRI score; liver biopsy scores; Model for End-stage Liver Disease (MELD); MELD excluding the International Normalized Ratio (MELD-XI); AST to platelet ratio index, and cardiac catheterization data were compared. RESULTS: Pretransplantation maximum MELD and MELD-XI was 15 and 16, respectively. Central venous pressures and VAST scores decreased significantly post-transplantation. In 5 paired studies, Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation. Arterially enhancing nodules on MRI persisted in 2 patients post-transplantation. Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens. CONCLUSIONS: Patients with FALD and MELD <15, MELD-XI <16, Fontan liver MRI score <10, and VAST score ≤2 can have successful short-term isolated heart transplantation outcomes. Liver MRI and VAST scores improved post-transplantation. Post-transplantation liver biopsy scores did not change significantly. Pretransplantation liver biopsy demonstrating fibrosis alone should not exclude consideration of isolated heart transplantation. The persistence of hepatic vascular remodeling and fibrosis post-isolated heart transplantation suggests that continued surveillance for hepatic complications post-transplantation for patients with Fontan is reasonable.


Asunto(s)
Procedimiento de Fontan/efectos adversos , Trasplante de Corazón , Hepatopatías/diagnóstico , Selección de Paciente , Adolescente , Ascitis/diagnóstico por imagen , Biopsia , Presión Venosa Central , Niño , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/patología , Hepatopatías/etiología , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Complicaciones Posoperatorias , Estudios Retrospectivos , Esplenomegalia/diagnóstico por imagen , Trombocitopenia , Várices/diagnóstico por imagen , Remodelación Vascular , Adulto Joven
6.
Transpl Infect Dis ; 23(1): e13435, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32748558

RESUMEN

Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation.


Asunto(s)
Infecciones por Adenoviridae , Absceso Hepático , Trasplante de Hígado , Adenoviridae , Infecciones por Adenoviridae/complicaciones , Adulto , Fiebre , Humanos , Absceso Hepático/etiología , Receptores de Trasplantes
7.
Pediatr Transplant ; 25(7): e14084, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34288298

RESUMEN

BACKGROUND: Pediatric acute liver failure (PALF) remains an enigmatic process of rapid end-organ dysfunction associated with a variety of pathologic conditions though the predominant cause is indeterminate. A growing body of research has identified mutations in the NBAS gene to be associated with recurrent acute liver failure and multi-systemic disease including short stature, skeletal dysplasia, facial dysmorphism, immunologic abnormalities, and Pelger-Huët anomaly. METHODS AND RESULTS: Here, we describe a 4-year-old girl who presented with dehydration in the setting of acute gastroenteritis and fever but went on to develop PALF on day 2 of hospitalization. She clinically recovered with supportive measures, but after discharge, had at least 2 additional episodes of PALF. Ultimately, she underwent liver transplant and her recurrent episodes of PALF did not recur throughout a 6-year follow-up period. Whole-exome sequencing post-liver transplant initially revealed two variants of uncertain significance in the NBAS gene. Parental studies confirmed the c.1549C > T(p.R517C; now likely pathogenic) variant from her mother and a novel c.4646T > C(p.L1549P) variant from her father. In silico analyses predicted these variants to have a deleterious effect on protein function. Consistent with previously characterized NBAS mutation-associated disease (NMAD), our patient demonstrated the following features: progeroid facial features, hypoplasia of the 12th ribs, Pelger-Huët anomaly on peripheral blood smear, and abnormal B and NK cell function. CONCLUSION: Altogether, we describe a novel pathogenic variant in the NBAS gene of a patient with NMAD and report the resolution of recurrent PALF secondary to NMAD following liver transplantation.


Asunto(s)
Fallo Hepático Agudo/genética , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Proteínas de Neoplasias/genética , Preescolar , Femenino , Humanos , Mutación , Recurrencia
8.
Am J Transplant ; 19(7): 1907-1911, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30125467

RESUMEN

The transplant community has debated the necessity and merits of broader organ distribution for several years, but the debate has been fundamentally shaped by inaccurate assessments of donor supply and demand. The possible legal requirements of distribution must be balanced with (a) the moral and statutory imperatives to reduce inequities resulting from socioeconomic disparity, and (b) the shortcomings of MELD in predicting mortality risk in rural areas. In this viewpoint, we use the example of liver transplantation to discuss the drivers of geographic disparity as a direct consequence of donation rates, local organ use, wealth, and poverty. Seen in this light, strategies seeking to equalize MELD at transplant across the United States risk severely exacerbating existing inequalities in access to health care.


Asunto(s)
Necesidades y Demandas de Servicios de Salud/organización & administración , Disparidades en Atención de Salud , Trasplante de Hígado/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/organización & administración , Listas de Espera , Geografía , Humanos , Regionalización , Estados Unidos
9.
Gastroenterology ; 154(8): 2178-2193, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29454797

RESUMEN

BACKGROUND & AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin (IL) 17, yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells. METHODS: We performed studies with Mdr2-/- and littermate FVB/NJ (control) mice. IL17 was measured in serum samples by an enzyme-linked immunosorbent assay. Mice were injected with neutralizing antibodies against the γδ T-cell receptor (TCR; anti-γδ TCR) or mouse IL17A (anti-IL17A). Livers were collected and bacteria were identified in homogenates by culture procedures; TCRγδ+ cells were isolated by flow cytometry. Fecal samples were collected from mice and analyzed by 16S ribosomal DNA sequencing. Cells were stimulated with antibodies or bacteria, and cytokine production was measured. We obtained tissues from 10 patients undergoing liver transplantation for primary sclerosing cholangitis or chronic hepatitis C virus infection. Tissues were analyzed for cytokine production by γδ TCR+ cells. RESULTS: Mdr2-/- mice had collagen deposition around hepatic bile ducts and periportal-bridging fibrosis with influx of inflammatory cells and increased serum levels of IL17 compared with control mice. Administration of anti-IL17A reduced hepatic fibrosis. Livers from Mdr2-/- mice had increased numbers of IL17A+ γδTCR+ cells-particularly of IL17A+ Vγ6Jγ1 γδ TCR+ cells. Fecal samples from Mdr2-/- mice were enriched in Lactobacillus, and liver tissues were enriched in Lactobacillus gasseri compared with control mice. Mdr2-/- mice also had increased intestinal permeability. The γδ TCR+ cells isolated from Mdr2-/- livers produced IL17 in response to heat-killed L gasseri. Intraperitoneal injection of control mice with L gasseri led to increased serum levels of IL17 and liver infiltration by inflammatory cells; injection of these mice with anti-γδ TCR reduced serum level of IL17. Intravenous injections of Mdr2-/- mice with anti-γδ TCR reduced fibrosis; liver levels of IL17, and inflammatory cells; and serum levels of IL17. γδTCR+ cells isolated from livers of patients with primary sclerosing cholangitis, but not hepatitis C virus infection, produced IL17. CONCLUSIONS: In Mdr2-/- mice, we found development of liver fibrosis and inflammation to require hepatic activation of γδ TCR+ cells and production of IL17 mediated by exposure to L gasseri. This pathway appears to contribute to development of cholestatic liver disease in patients.


Asunto(s)
Colestasis/patología , Microbioma Gastrointestinal , Interleucina-17/metabolismo , Linfocitos Intraepiteliales/metabolismo , Cirrosis Hepática/patología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Anciano , Animales , Conductos Biliares/citología , Conductos Biliares/inmunología , Conductos Biliares/microbiología , Células Cultivadas , Colangitis Esclerosante/microbiología , Colangitis Esclerosante/patología , Colangitis Esclerosante/cirugía , Colestasis/inmunología , Colestasis/microbiología , Colestasis/cirugía , Modelos Animales de Enfermedad , Enfermedad Hepática en Estado Terminal/microbiología , Enfermedad Hepática en Estado Terminal/patología , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Hepatitis C Crónica/patología , Hepatitis C Crónica/cirugía , Hepatitis C Crónica/virología , Humanos , Interleucina-17/antagonistas & inhibidores , Interleucina-17/sangre , Interleucina-17/inmunología , Lactobacillus gasseri/inmunología , Hígado/citología , Hígado/inmunología , Hígado/microbiología , Hígado/patología , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Cirrosis Hepática/cirugía , Trasplante de Hígado , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T gamma-delta/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Adulto Joven , Miembro 4 de la Subfamilia B de Casete de Unión a ATP
10.
Hepatology ; 65(2): 661-677, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27774611

RESUMEN

Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8+ T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4+ T-cell help. Elevated CD4+ forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8+ T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4+ Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4+ Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. CONCLUSION: Liver disease elicits alterations in the intrahepatic CD4+ T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65:661-677).


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Factores de Transcripción Forkhead/metabolismo , Inmunoglobulina G/inmunología , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Análisis de Varianza , Animales , Células Cultivadas , Enfermedad Crónica , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Ensayo de Immunospot Ligado a Enzimas , Citometría de Flujo , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/patología , Hepatocitos , Humanos , Inmunoglobulina G/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Estadísticas no Paramétricas , Linfocitos T Reguladores/inmunología
11.
J Virol ; 90(18): 8372-80, 2016 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-27412592

RESUMEN

UNLABELLED: A panel of Sindbis virus mutants that were suspected to have deficiencies in one or more aspects of their replication cycles was examined in baby hamster kidney (BHK) cells. These included an amino acid deletion (ΔH230) and substitution (H230A) in the Sindbis glycoprotein E1_H230 and similar mutants in E2_G209 (G209A, G209D, and ΔG209). Neither H230 mutation produced a measurable titer, but repeated passaging of the H230A mutant in BHK cells produced a second-site compensatory mutant (V231I) that partially rescued both H230 mutants. Electron micrograph (EM) images of these mutants showed assembled viral nucleocapsids but no completed, mature virions. EM of the compensatory mutant strains showed complete virus particles, but these now formed paracrystalline arrays. None of the E2_G209 substitution mutants had any effect on virus production; however, the deletion mutant (ΔG209) showed a very low titer when grown at 37°C and no titer when grown at 28°C. When the deletion mutant grown at 28°C was examined by EM, partially budded virions were observed at the cell surface. (35)S labeling of this mutant confirmed the presence of mutant virus protein in the transfected BHK cell lysate. We conclude that H230 is essential for the assembly of complete infectious Sindbis virus virions and that the presence of an amino acid at E2 position 209 is required for complete budding of Sindbis virus particles although several different amino acids can be at this location without affecting the titer. IMPORTANCE: Our data show the importance of single-site mutations at E1_H230 and E2_G209 in Sindbis virus glycoproteins. These sites have been shown to affect assembly and antibody binding in previous studies. Our data indicate that mutation of one histidine residue in E1 is detrimental to the assembly of Sindbis virus particles in baby hamster kidney cells. Repeated passaging leads to a second-site substitution that partially restores the titer although EM still shows an altered phenotype. Substitutions at position G209 in E2 have no effect on titer, but deletion of this residue greatly reduces titer and again prevents assembly. When this mutant is grown at a lower temperature, virus particles bud from the host cell, but budding arrests before the progeny virus escapes. These results allow us to conclude that these sites have essential roles in assembly, and E2_G209 shows us a new viral egress phenotype.


Asunto(s)
Glicoproteínas de Membrana/metabolismo , Proteínas Mutantes/metabolismo , Virus Sindbis/fisiología , Proteínas del Envoltorio Viral/metabolismo , Ensamble de Virus , Liberación del Virus , Animales , Células Cultivadas , Cricetinae , Glicoproteínas de Membrana/genética , Microscopía Electrónica , Proteínas Mutantes/genética , Mutación Missense , Mutación Puntual , Eliminación de Secuencia , Virus Sindbis/genética , Virus Sindbis/ultraestructura , Supresión Genética , Temperatura , Proteínas del Envoltorio Viral/genética , Carga Viral , Virión/ultraestructura , Cultivo de Virus
12.
Pediatr Transplant ; 21(6)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28626929

RESUMEN

Desmoplastic spindle cell tumors of liver are rare tumors of low malignant potential characterized by well-demarcated nests of spindle and epithelioid cells in a dense desmoplastic stroma. While surgery remains the definitive treatment, there have been reports of tumor recurrence locally and metastasis which respond poorly to chemotherapy. Hepatic transplant has been attempted in cases of recurrence or large size of primary tumor. Long-term follow-up and imaging surveillance are required as these tumors have shown a tendency for recurrence many years after initial therapy.


Asunto(s)
Síndrome de Beckwith-Wiedemann/complicaciones , Síndrome de Cushing/etiología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Neoplasias Glandulares y Epiteliales/cirugía , Adolescente , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Glandulares y Epiteliales/complicaciones
13.
Hepatology ; 61(3): 843-56, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25331524

RESUMEN

UNLABELLED: Chronic liver disease is characterized by the liver enrichment of myeloid dendritic cells (DCs). To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem cell marker CD34. In patients with endstage liver disease, liver CD34+ cells were comprised of two subsets, designated CD34+CD146+ and CD34+CD146-, and hematopoietic function was restricted to CD34+CD146- cells. Liver CD34 frequencies were reduced during nonalcoholic steatohepatitis (NASH) and chronic hepatitis C virus (HCV) compared to alcohol liver disease (ALD), and this reduction correlated with viral load in the HCV cohort. To better understand the relationship between liver CD34+CD146+ and CD34+CD146- subsets and any effects of disease on CD34 development, we used gene expression profiling and computational modeling to compare each subset during ALD and HCV. For CD34+CD146+ cells, increased expression of endothelial cell genes including von Willebrand factor, VE-cadherin, and eNOS were observed when compared to CD34+CD146- cells, and minimal effects of ALD and HCV diseases on gene expression were observed. Importantly for CD34+CD146- cells, chronic HCV was associated with a distinct "imprint" of programs related to cell cycle, DNA repair, chemotaxis, development, and activation, with an emphasis on myeloid and B lymphocyte lineages. This HCV signature was further translated in side-by-side analyses, where HCV CD34+CD146- cells demonstrated superior hematopoietic growth, colony formation, and diversification compared to ALD and NASH when cultured identically. Disease-associated effects on hematopoiesis were also evident by phenotypic alterations in the expression of CD14, HLA-DR, and CD16 by myeloid progeny cells. CONCLUSION: Etiology drives progenitor fate within diseased tissues. The liver may be a useful source of hematopoietic cells for therapy, or as therapeutic targets.


Asunto(s)
Células Madre Hematopoyéticas/fisiología , Hepacivirus/fisiología , Hígado/citología , Biología de Sistemas , Antígenos CD34/análisis , Antígeno CD146/análisis , Linaje de la Célula , Hematopoyesis , Hepatitis C Crónica/fisiopatología , Humanos , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Carga Viral
14.
J Surg Oncol ; 109(6): 533-41, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24347475

RESUMEN

BACKGROUND: Management of hepatocellular carcinoma (HCC) in the Model for End-Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes were compared for patients undergoing transplant versus resection at a single institution in a UNOS region with short wait times for organ availability. METHODS: All patients who underwent resection of HCC from January 2000 to August 2012 and patients who underwent transplant post-January 2006, during the Milan Criteria (MC)-based MELD exception policy for HCC, were identified. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Two hundred fifty-seven patients were analyzed, of whom 131 underwent transplant and 126 underwent resection. All transplant patients met MC; 45 (36%) resection patients met MC. Median follow-up time was 30 months. Median wait time to transplant was 55 days; no patients dropped off the waitlist while awaiting an organ. Among patients meeting MC, transplant demonstrated significantly greater 5-year OS (65.7% vs. 43.8%; P = 0.005) and RFS (85.3% vs. 22.7%; P < 0.001) versus resection. For patients with hepatitis C, transplant (n = 87) demonstrated significantly improved 5-year outcomes compared to patients meeting MC who underwent resection (n = 21; OS: 63.5% vs. 23.3%; P = 0.001; RFS: 83.5% vs. 23.7%; P < 0.001). CONCLUSION: In a region with short waitlist times for organ availability, liver transplant is associated with improved survival compared to resection for HCC within MC and should be considered for all patients meeting MC, particularly those with hepatitis C.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Hepatectomía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/mortalidad , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Retrospectivos , Listas de Espera
15.
Clin Transplant ; 27(5): 693-700, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23924066

RESUMEN

BACKGROUND: Alemtuzumab (AZ) is a monoclonal anti-CD52 antibody used as an induction agent in organ transplantation. Few studies have analyzed this agent in the context of simultaneous kidney-pancreas transplantation (SPKT). METHODS: We examined US registry data of SPKT recipient outcomes from January 2002 to October 2009 stratified by induction agent including AZ, other T-cell-depleting agents combined (T cell), IL2 receptor blockade (IL-2RAb), and no induction (none). RESULTS: Of 6860 SPKT recipients, induction therapy was AZ in 10%, T cell in 49%, IL-2RAb in 18%, and none in 22%. On multivariate analysis, there were no significant differences in overall patient survival, pancreas or renal allograft survival, or delayed renal graft function for the three induction groups compared with no induction. Rehospitalization within six months of transplantation occurred more often with AZ (51%) T cell (52%), and IL-2RAB (45%) compared with none (41%; p < 0.0001). On multivariate analysis, there was a significant higher odds of six-month rehospitalization with AZ (aOR 1.40, 95%CI 1.14-1.71), IL-2RAb (aOR 1.20, 95%CI 1.01-1.42-1.20), and other T-cell-depleting agents (aOR 1.50, 95%CI 1.31-1.73) compared with none. Median length of stay was significantly shorter in the AZ (8 d) compared with the IL-2RAb (9 d), T cell (10 d), and none (10 d) groups (p < 0.0001). CONCLUSIONS: There are no differences in patient, pancreas or renal allograft survival using AZ induction. AZ may confer an advantage in the perioperative period as evidenced by a decreased hospital length of stay. However, this benefit may be lost due to more frequent rehospitalizations.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Rechazo de Injerto/inmunología , Trasplante de Riñón , Trasplante de Páncreas , Receptores de Interleucina-2/inmunología , Linfocitos T/inmunología , Adulto , Alemtuzumab , Femenino , Estudios de Seguimiento , Rechazo de Injerto/mortalidad , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Hospitalización , Humanos , Masculino , Pronóstico , Sistema de Registros , Inducción de Remisión , Tasa de Supervivencia
16.
Transpl Int ; 26(10): 963-72, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23819508

RESUMEN

Outcomes of old-donor simultaneous pancreas-kidney transplantation (SPKT) have not been thoroughly studied. Scientific Registry of Transplant Recipients data reported for SPKT candidates receiving dialysis wait-listed between 1993 and 2008 (n = 7937) were analyzed for outcomes among those who remained listed (n = 3301) and of SPKT recipients (n = 4636) using multivariable time-dependent regression models. Recipients were stratified by donor/recipient age (cutoff 40 years) into: young-to-young (n = 2099), young-to-old (n = 1873), old-to-young (n = 293), and old-to-old (n = 371). The overall mortality was 12%, 14%, 20%, and 24%, respectively, for those transplanted, and 50% for those remaining on the waiting list. On multivariable analysis, old-donor SPKT was associated with significantly higher overall risks of patient death, death-censored pancreas, and kidney graft failure in both young (73%, 53%, and 63% increased risk, respectively) and old (91%, 124%, and 85% increased risk, respectively) recipients. The adjusted relative mortality risk was similar for recipients of old-donor SPKT compared with wait-listed patients including those who subsequently received young-donor transplants (aHR 0.95; 95% CI 0.78, 1.12) except for candidates in OPOs with waiting times ≥604 days (aHR 0.65, 95% CI 0.45-0.94). Old-donor SPKT results in significantly worse graft survival and patient mortality without any waiting-time benefit as compared to young-donor SPKT, except for candidates with expected long waiting times.


Asunto(s)
Diabetes Mellitus Tipo 1/terapia , Fallo Renal Crónico/terapia , Trasplante de Riñón/métodos , Trasplante de Páncreas/métodos , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Femenino , Humanos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Trasplante de Páncreas/mortalidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Diálisis Renal/métodos , Factores de Riesgo , Resultado del Tratamiento , Estados Unidos , Listas de Espera , Adulto Joven
17.
Tech Vasc Interv Radiol ; 26(4): 100922, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38123284

RESUMEN

Liver transplantation is a technically demanding surgical procedure with known complications, and the optimal approach to addressing vascular and biliary complications requires a coordinated effort between surgical and interventional radiology teams. Vascular complications involving the hepatic artery, portal vein, or hepatic veins can be characterized by their mechanism, chronicity, and timing of presentation. These factors help determine whether the optimal therapeutic approach is surgical or endovascular. Very early presentation in the perioperative period favors surgical revision, while later presentation is best addressed endovascularly. Biliary complications can be categorized as leaks or strictures, and coordinated surgical, endoscopic, and percutaneous management is needed to address these types of complications. Through advances in technique and the management of complications, outcomes after liver transplantation continue to improve.


Asunto(s)
Enfermedades de las Vías Biliares , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Enfermedades de las Vías Biliares/terapia , Arteria Hepática , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos
18.
Hepatol Commun ; 7(9)2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37655982

RESUMEN

BACKGROUND: Split liver transplantation (SLT), where a single donor liver is divided for transplantation to 2 recipients, has the potential to increase the availability of size-matched livers for pediatric candidates and expand the supply of donor organs available for adult candidates. Although SLT is a well-established technique, the number of SLTs has remained flat during the past 2 decades, partly due to concerns about the posttransplant survival of SLT recipients compared with whole liver transplantation (WLT) recipients. Prior work on SLT versus WLT survival analysis had limitations because, for pediatric recipients, it did not consider the correlations between donor age/weight and the allograft type, and for adult recipients, it may have included records where the donor livers did not meet the split liver criteria (splittable). METHODS: Using the Organ Procurement and Transplantation Network's database (2003-2019), this study analyzes and compares (i) key characteristics of donors and recipients, (ii) donor-recipient match dynamics (organ offers and accept/decline decisions), and (iii) recipient posttransplant survival, for SLT and WLT. RESULTS AND CONCLUSIONS: The results in this study show that the posttransplant survival of SLT and WLT recipients is similar (controlling for other confounding factors that may impact posttransplant survival), highlighting the importance of SLT for increasing the liver supply and potential benefits for both pediatric and adult candidates.


Asunto(s)
Trasplante de Hígado , Adulto , Humanos , Niño , Donadores Vivos , Hígado/cirugía , Trasplante Homólogo , Ácido Láctico
19.
Clin Transplant ; 26(4): E372-80, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22672515

RESUMEN

Despite a variety of urinary tract reconstructive techniques, urinary complications are the most frequent technical adverse event following kidney transplantation. We examined outcomes of two ureteroneocystostomy techniques, the full-thickness (FT) technique and the Lich-Gregoir (LG) technique in 634 consecutive kidney-alone transplants (327 FT and 307 LG) between December 2006 and December 2010. Urological complications at one yr post-transplantation occurred in 27 cases (4.3%) including 16 ureteral strictures (2.5%), four ureteral obstructions (0.6%) owing to donor-derived stones or intrinsic hematoma, and seven urine leaks (1.1%). Compared with LG, the FT technique was associated with similar proportions of ureteral complications overall (3.9% vs. 4.6%, p = 0.70), ureteral strictures (3.7% vs. 1.3%, p = 0.08), urinary stones/hematoma (1.0% vs. 0.3%, p = 0.36), and overall urinary leaks (1.6% vs. 0.6%, p = 0.22); however, the FT technique was associated with somewhat fewer urine leaks at the ureterovesical junction (0% vs. 1.3%, p = 0.05). There were no differences between the two groups in terms of length of stay, delayed graft function, urinary tract infection with the first post-transplant year, estimated glomerular filtration rate, and overall graft and patient survival. The FT technique of ureteroneocystostomy is technically simple to perform and has a similar incidence of urinary complications compared with the LG technique.


Asunto(s)
Cistostomía/mortalidad , Funcionamiento Retardado del Injerto/etiología , Enfermedades Renales/complicaciones , Trasplante de Riñón/efectos adversos , Enfermedades Ureterales/etiología , Ureterostomía/mortalidad , Adulto , Estudios de Casos y Controles , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/cirugía , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Incidencia , Enfermedades Renales/cirugía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Enfermedades Ureterales/epidemiología , Enfermedades Ureterales/cirugía
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