Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Transplante de Fígado/estatística & dados numéricos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Diagnóstico Diferencial , Feminino , Hepatite B/complicações , Hepatite B/diagnóstico , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Sensibilidade e EspecificidadeAssuntos
Neoplasias/epidemiologia , Transplante de Órgãos/efeitos adversos , Humanos , Neoplasias Renais/epidemiologia , Metástase Neoplásica , Neoplasias/etiologia , Neoplasias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Doadores de TecidosAssuntos
Carcinoma Hepatocelular/cirurgia , Hepatite B Crônica/cirurgia , Hepatite C Crônica/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/estatística & dados numéricos , Austrália/epidemiologia , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Seleção de Pacientes , Resultado do TratamentoRESUMO
Macroregenerative nodules (MRN) have been detected with increased incidence in explanted livers since orthotopic liver transplantation (OLTx) has become a routine treatment for end-stage liver disease. Autopsy series suggest that MRN may be more common than once thought, and several studies point to the malignant potential of these lesions. With increasing waiting times for OLTx, the propensity for these premalignant lesions to arise in cirrhotic livers has important implications for the supervision of patients on OLTx waiting lists. We present here a striking example of a MRN and review a topic that is generating considerable interest.
Assuntos
Hepatopatias/patologia , Hepatopatias/cirurgia , Transplante de Fígado , Fígado/patologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , HiperplasiaRESUMO
Liver transplantation (LT) in some rat strain combinations can induce tolerance to other organ grafts of liver donor strain. The aim of the study was to examine the effect of LT on islet allografts. Islets were isolated by collagenase digestion and purified by dextran-gradient separation. Islets from two donor animals (>2,000) were transplanted under the left kidney capsule of streptozotocin-induced diabetic rats. The liver was implanted orthotopically. The results showed that concurrent LT and islet transplantation (IT) prolonged survival of islet allografts modestly, but islet allografts survived indefinitely when LT was performed before or after IT. LT delayed or reversed ongoing islet graft rejection. IT could trigger rejection in otherwise tolerated liver grafts. We conclude that sequential IT-LT or LT-IT can induce islet allograft tolerance or liver rejection and that the mechanisms involved may differ from those involved with LT simultaneously with either IT or vascularized organ grafts.
Assuntos
Diabetes Mellitus Experimental/imunologia , Transplante de Fígado/imunologia , Tolerância ao Transplante/imunologia , Animais , Diabetes Mellitus Experimental/patologia , Sobrevivência de Enxerto/imunologia , Insulina/metabolismo , Transplante das Ilhotas Pancreáticas/imunologia , Transplante das Ilhotas Pancreáticas/patologia , Transplante de Fígado/patologia , Masculino , Ratos , Ratos Endogâmicos , Transplante HomólogoRESUMO
Orthotopic partial liver transplantation (PLT) models were developed in rats to explore the unique role of the liver in transplant tolerance. In PVG rats, syngeneic PLT established that surgical reduction to one-third of the liver and orthotopic transplantation permitted survival. Allogeneic PLT in the PVG to DA liver-tolerant model, both 50% and 33%, did not affect the tolerogeneic property of the liver, with all PLT recipients surviving indefinitely. Blood samples taken at various time points for detection of donor cells using flow cytometry showed a steady increase in donor cell chimerism in both PLT and whole liver transplantation (WLT) recipients that persisted throughout the 3-month observation period. At each time point, the level of donor cell chimerism in PLT was higher than that in WLT. We conclude that transplantation of one-third of the liver is compatible with survival in rats. Reduction of antigenic load by means of hepatectomy does not affect the tolerogenic effect of the liver in the PVG to DA LT model because of the remarkable regeneration capability of the liver. Peripheral chimeric levels increase progressively after WLT, suggesting that this is an ongoing immunological phenomenon. The earlier and increased chimerism after PLT may be associated with liver regeneration.
Assuntos
Quimera , Epitopos/imunologia , Transplante de Fígado/imunologia , Tolerância ao Transplante/imunologia , Animais , Sobrevivência de Enxerto/imunologia , Regeneração Hepática/imunologia , Masculino , Ratos , Ratos Endogâmicos , Transplante Homólogo , Transplante IsogênicoRESUMO
BACKGROUND: The effects of immunosuppressive drugs on transplant tolerance have not been extensively studied, although their effect on rejection is well established. METHODS: We examined the effects of a short course of treatment with the immunosuppressive drug methylprednisolone (MP) on the survival of PVG liver allografts in Dark Agouti (DA) recipients that accepted the livers and in Lewis recipients that rejected the livers. Infiltration of liver allografts was examined by immunohistochemical staining of liver sections, and apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling. RESULTS: A 5-day course of MP (days 0 to 4) led to rejection of four of six livers (mean survival time [MST] 99 days) in DA recipients compared with long-term survival (MST >100 days) in untreated animals. Delayed administration of MP (days 3 to 7) exacerbated rejection in DA recipients, and all eight animals rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not significantly prolong survival when administered from days 0 to 4 (MST 13 days), although delay of administration improved the outcome. Treatment from days 3 to 7 resulted in an MST of 21 days, whereas treatment from days 7 to 11 resulted in an MST of 41.5 days. MP treatment from day 3 to day 7 reduced T cells and interleukin 2 receptor-expressing cells but increased the numbers of apoptotic cells infiltrating both DA and Lewis strain allografts. CONCLUSIONS: These results show that immunosuppression with MP inhibits both spontaneous tolerance and rejection of liver allografts in a rat model and question the efficacy of administering MP to all liver allograft recipients from the time of transplantation.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Fígado , Metilprednisolona/uso terapêutico , Animais , Apoptose , Movimento Celular , Esquema de Medicação , Imuno-Histoquímica , Leucócitos/patologia , Leucócitos/fisiologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos , Baço/patologia , Doadores de Tecidos , Tolerância ao Transplante/efeitos dos fármacos , Transplante HomólogoAssuntos
Sobrevivência de Enxerto/imunologia , Transplante de Coração/imunologia , Transplante de Rim/imunologia , Tolerância ao Transplante/imunologia , Animais , Apoptose , Movimento Celular , Rejeição de Enxerto , Marcação In Situ das Extremidades Cortadas , Leucócitos/fisiologia , Masculino , Ratos , Fatores de TempoAssuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Fígado , Linfócitos/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Sobrevivência de Enxerto/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/citologia , Masculino , Modelos Animais , Ratos , Ratos Endogâmicos Lew , TripterygiumAssuntos
Transplante de Rim/estatística & dados numéricos , Neoplasias/epidemiologia , Sistema de Registros/estatística & dados numéricos , Austrália/epidemiologia , Humanos , Transplante de Rim/efeitos adversos , Neoplasias/mortalidade , Nova Zelândia/epidemiologia , Prognóstico , Recidiva , Diálise Renal/mortalidade , Diálise Renal/estatística & dados numéricos , Análise de Sobrevida , Fatores de TempoAssuntos
Neoplasias/etiologia , Transplante de Órgãos/efeitos adversos , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Coriocarcinoma/etiologia , Coriocarcinoma/mortalidade , Erros de Diagnóstico , Humanos , Terapia de Imunossupressão , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Transplante de Rim/efeitos adversos , Melanoma/etiologia , Melanoma/mortalidade , Neoplasias/mortalidade , Neoplasias/terapia , Ohio/epidemiologia , Sistema de Registros/estatística & dados numéricosAssuntos
Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Neoplasias/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/etiologia , Glomerulonefrite/terapia , Humanos , Terapia de Imunossupressão/efeitos adversos , Incidência , Lactente , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/epidemiologia , Razão de Chances , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Análise de Regressão , Diálise Renal , Fatores de RiscoRESUMO
The growing imbalance between the number of cadaveric organ donors and recipients has led to an increasing use of high-risk donors as an option to expand the donor pool. The aim of this study was to evaluate our experience with the use of older liver (donor>50 yr of age) allografts. The medical records, postreperfusion biopsies and laboratory results were reviewed of the 393 patients who underwent orthotopic liver transplantation between 1986 and 1997. The outcome of the 61 patients who received older livers (OL) was compared to that of the other 332 recipients. Increasing use of OL was evident from 1992 onwards. Recipients of OL were older than recipients of younger livers (YL, p<0.001) and more commonly had underlying chronic viral hepatitis (CVH) or fulminant hepatic failure (p<0.05). Patient and allograft survival were only slightly less in recipients of OL versus YL (p=NS). Although postperfusion biopsies showed more damage in OL than YL allografts (p<0.05), this was not associated with increased primary graft failure. OL allografts can be transplanted with acceptable results into recipients without the concern of early allograft loss. SUMMARY OF ARTICLE: This report of one centre's experience with 61 recipients of older donor liver allografts identifies recipient factors that may also have a negative impact on allograft outcome. These factors include a diagnosis of either CVH or fulminant hepatic failure at the time of transplantation. Postreperfusion biopsies of older donor allografts tend to show more damage, but this is not associated with primary non-function.
Assuntos
Fatores Etários , Sobrevivência de Enxerto , Transplante de Fígado , Doadores de Tecidos , Adolescente , Adulto , Cadáver , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Liver allografts in spontaneously tolerant strain combinations can protect other organs of the same donor origin from rejection and reverse ongoing rejection in previously placed grafts. The aims of this study were to examine whether liver allografts have the same protective effect on islet allografts and to investigate the underlying mechanisms. METHODS: PVG islets were transplanted beneath the kidney capsule of streptozotocin-induced diabetic DA rats with or without liver allografting. The cellular infiltrate, and the extent of apoptosis and of Fas ligand (FasL) expression in the islet grafts were evaluated on days 2, 4, and 7 after transplantation by means of immunostaining and the in situ terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay. Donor and recipient mixed lymphocyte reactions (MLR) were determined at 7 days or 100 days after islet transplantation. RESULTS: Islet allografts transplanted alone were rapidly rejected within 5-8 days. Rejection was delayed, but not prevented, when islets were transplanted simultaneously with the liver. Liver transplantation 1 month before islet transplantation resulted in long-term survival (>100 days) of islet grafts in three of seven animals, whereas the other four died of liver rejection with functional islet grafts. Liver transplantation on day 4 after islet grafting reversed ongoing islet rejection and led to indefinite islet graft survival in three of seven cases. There was a progressive increase of cellular infiltration in all of the islet allografts, but the intensity of the infiltrate did not correlate with the outcome of the islet allografts. Islet rejection was characterized by an early dominance of monocytes/macrophages and CD25+ T cells in the infiltrates, a high incidence of apoptotic beta cells in grafts, and a sensitized status in the MLR. Tolerance of islet allografts was associated with increased numbers of dendritic cells in the graft infiltrates, up-regulation of FasL, and prominent apoptosis of alloreactive leukocytes in the islet grafts, as well as donor-specific MLR suppression in long-term survivors. CONCLUSIONS: These results demonstrate that the extent of the protective effect of liver transplantation on islet allografts varies with the time of liver grafting, ranging from delay in islet rejection to complete islet acceptance. Islet graft tolerance induced by liver transplantation is the result of an immune process that involves up-regulation of Fas ligand expression on, and apoptosis of, islet graft infiltrating lymphocytes.