RESUMEN
BACKGROUND & AIMS: We have observed a high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in heart transplant recipients (HTRs). The aim of this study was to assess the epidemiology, natural history, and clinical and biological characteristics of viral hepatitis in HTRs. METHODS: From 1983 to 1992, 874 patients underwent heart transplantation at the Pitié-Salpêtrière Hospital, Paris, France, 459 of whom qualified for analysis. A total of 140 patients had posttransplantation hepatitis B, C, or non-A-E. Sixty-nine patients developed HBV infection, 49 HCV infection, 11 HBV-HCV coinfection, and 11 non-A-E hepatitis. RESULTS: HBV was transmitted nosocomially from patient to patient, most likely during endomyocardial biopsies. HCV was mainly transmitted through blood transfusions or the transplanted organ. Clinical and biological findings after 2 years of follow-up showed that 3 patients with an HBV genotype A precore mutant had severe or subfulminant hepatitis and that patients with HBV and HCV infection always progressed to chronicity. In general, patients had mild alanine aminotransferase level increases, a high level of viral replication, and few severe histologic lesions, except for patients infected by precore HBV mutants. Patients coinfected by HBV and HCV tended to have more severe liver lesions. The survival rate 5 years after transplantation in patients with viral hepatitis (HBV, 81%; HCV, 89%; HBV and HCV coinfection, 100%; non-A-E hepatitis, 73%) was similar to that in patients without liver test abnormalities (76%). The actuarial survival curve was also similar in patients with or without liver test abnormalities. CONCLUSIONS: In our experience, histologic liver lesions do not progress rapidly in patients with post-heart transplant infection caused by HBV or HCV. HBV or HCV infection seems to have little impact on the 5-year survival rate of HTRs.
Asunto(s)
Trasplante de Corazón , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Complicaciones Posoperatorias/veterinaria , Adolescente , Adulto , Anciano , Progresión de la Enfermedad , Transmisión de Enfermedad Infecciosa , Femenino , Trasplante de Corazón/mortalidad , Trasplante de Corazón/fisiología , Hepatitis B/mortalidad , Hepatitis B/fisiopatología , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Hepatitis B Crónica/fisiopatología , Hepatitis C/mortalidad , Hepatitis C/fisiopatología , Hepatitis C Crónica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Paris , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.
Asunto(s)
Colestasis/inducido químicamente , Ciclosporina/efectos adversos , Trasplante de Corazón , Hepatitis Crónica/complicaciones , Inmunosupresores/efectos adversos , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Ácidos y Sales Biliares/sangre , Bilirrubina/sangre , Ácido Quenodesoxicólico/sangre , Colestasis/sangre , Ácido Cólico , Ácidos Cólicos/sangre , Cromatografía Líquida de Alta Presión , Ayuno , Femenino , Ácido Glicocólico/sangre , Hepatitis Crónica/sangre , Humanos , Ácido Litocólico/sangre , Masculino , Persona de Mediana Edad , Espectrofotometría Ultravioleta , Ácido Taurocólico/sangre , Ácido Ursodesoxicólico/sangreAsunto(s)
Cardiomiopatías/cirugía , Daunorrubicina/efectos adversos , Doxorrubicina/efectos adversos , Trasplante de Corazón , Neoplasias/tratamiento farmacológico , Análisis Actuarial , Adulto , Azatioprina/uso terapéutico , Cardiomiopatías/inducido químicamente , Ciclosporina/uso terapéutico , Femenino , Trasplante de Corazón/inmunología , Trasplante de Corazón/mortalidad , Humanos , Terapia de Inmunosupresión/métodos , Masculino , Prednisolona/uso terapéutico , Tasa de SupervivenciaAsunto(s)
Antígenos CD/sangre , Rechazo de Injerto/diagnóstico , Antígenos HLA-DR/sangre , Trasplante de Corazón/inmunología , Linfocitos/inmunología , Anticuerpos Monoclonales , Quimioterapia Combinada , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/uso terapéutico , Valor Predictivo de las Pruebas , PronósticoRESUMEN
PURPOSE: Organ recipients are at a high risk of post-transplant lymphoproliferative disorders (PTLDs) as a complication of immunosuppressive therapy. We report the incidence, clinical presentation, pathologic findings, treatment, and outcome for 24 cases of PTLD observed at our institution. PATIENTS AND METHODS: Twenty-four (1.7%) of 1,385 organ transplant recipients developed PTLDs. Dosages of immunosuppressive drugs were reduced in 19 patients. Treatment consisted of anti-B-cell monoclonal antibodies (12 patients), and/or chemotherapy (eight patients), or surgery (two patients). RESULTS: The median time between grafting and the onset of PTLD was 210 days. Tumors were classified as monomorphic and polymorphic in nine and 15 cases, respectively. Three of 24 cases were of T-cell origin. Genotypic studies confirmed the monoclonality of the tumors in 11 cases among 14 PTLDs tested. Epstein-Barr virus (EBV) infection was associated with 70% of B-cell PTLDs tested. The overall survival duration was 5 months. Ten patients are alive and disease-free with a median follow-up time of 37 months; most were treated with anti-B-cell antibodies. Two other patients died in complete remission of unrelated causes at 33 and 38 months. CONCLUSION: Anti-B-cell monoclonal antibody therapy seems to be effective in PTLD, even in monoclonal B-cell forms, but other approaches will be necessary to improve survival further.
Asunto(s)
Trastornos Linfoproliferativos/etiología , Trasplante de Órganos/efectos adversos , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Linfocitos B/inmunología , Femenino , Trasplante de Corazón/efectos adversos , Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4 , Humanos , Terapia de Inmunosupresión/efectos adversos , Trasplante de Riñón/efectos adversos , Trasplante de Pulmón/efectos adversos , Linfoma de Células B/etiología , Linfoma de Células B/terapia , Linfoma de Células T/etiología , Linfoma de Células T/terapia , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Infecciones Tumorales por Virus/complicacionesRESUMEN
Both cytokines produced by activated monocytes and T cells and direct cell-to-cell contact with antigen-primed T cells during inflammatory reactions are known to induce the expression of several adhesion proteins on endothelial cells. In this prospective longitudinal study, we analyzed the expression of ELAM-1, VCAM-1, and ICAM-1 on myocardial allograft biopsy specimens taken from 16 cardiac allograft recipients either for routine monitoring or for the investigation of suspected rejection. Infiltrating T cells were identified using anti-CD3 antibodies. Three to six sequential biopsies taken at one-week intervals were analyzed by means of conventional histology and immunohistochemistry. Seven patients did not develop rejection during the study; their biopsies were negative for VCAM-1 and ELAM-1, although faint ICAM-1 staining was present on capillaries, reflecting constitutive expression. Three patients entered the study with clear-cut clinical and histologic signs of acute rejection. Intense VCAM-1 and ICAM-1 expression was detected on capillary and postcapillary venules, together with a heavy CD3+ T cell infiltrate; VCAM-1 was also expressed on arteriolar endothelial cells. ELAM-1 was undetectable in all three cases. Six patients developed acute rejection during the course of the study. In four, ELAM-1 and VCAM-1 were expressed on both capillary and postcapillary venules one or two weeks before the histological diagnosis of rejection (heavy CD3+ cell infiltrate). Importantly, ELAM-1 expression was short-lived and had disappeared by the time CD3+ cellular infiltrate was detected, thus extending in vivo the finding that ELAM-1 expression is usually transient in vitro. Only VCAM-1 expression was observed in the other two patients, one week prior to the histological diagnosis of rejection. These results suggest that ELAM-1 and VCAM-1 might represent early predictive markers of acute cardiac allograft rejection. ELAM-1 expression is, however, usually transient, necessitating frequent testing.
Asunto(s)
Moléculas de Adhesión Celular/fisiología , Trasplante de Corazón/inmunología , Adolescente , Adulto , Biopsia , Complejo CD3/sangre , Moléculas de Adhesión Celular/sangre , Selectina E , Endotelio Vascular/química , Endotelio Vascular/inmunología , Rechazo de Injerto/sangre , Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Antígenos HLA-DR/sangre , Humanos , Persona de Mediana Edad , Receptores de Interleucina-2/análisis , Trasplante Homólogo , Molécula 1 de Adhesión Celular VascularRESUMEN
The diagnosis of acute rejection in heart allograft recipients receiving cyclosporine is still an important challenge. The poor diagnostic value of clinical signs and the ECG means that regular endomyocardial biopsies must be performed. Despite their diagnostic value during the first year after transplantation, endomyocardial biopsies are less sensitive there after and currently suffer from the lack of a universally accepted histological classification. Doppler echocardiography can be used for routine surveillance and has proven reliable for the diagnosis of acute rejection with various clinical presentations when used in conjunction with endomyocardial biopsies. Immunohistological examination of myocardial specimens can further increase the sensitivity of histological diagnosis. Similarly, immunoscintigraphy with indium 111-labelled antimyosin antibodies is of value for the prediction of acute rejection after the first year. Therapeutic approaches have been standardized, but must still be tailored to the individual patient according to the severity of the rejection and the presence of associated infection and/or metabolic disturbances.
Asunto(s)
Rechazo de Injerto/diagnóstico , Trasplante de Corazón/efectos adversos , Enfermedad Aguda , Ecocardiografía , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/patología , Rechazo de Injerto/terapia , HumanosAsunto(s)
Trasplante de Corazón/efectos adversos , Hepatitis B/epidemiología , Reacción a la Transfusión , Adulto , ADN Viral/sangre , ADN Viral/genética , Hepatitis B/etiología , Hepatitis B/genética , Hepatitis B/transmisión , Antígenos de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Humanos , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
Trasplante de Corazón , Hepatitis B/etiología , Reacción a la Transfusión , Adulto , Donantes de Sangre , Femenino , Hepatitis B/sangre , Humanos , MasculinoRESUMEN
With no additional therapy, mild acute cardiac allograft rejection progresses in 30 per cent of the cases towards moderate rejection. Three hundred mild rejections which occurred in 120 patients between May 1987 and May 1989 were studied and divided into 3 groups according to their treatment. Group I rejections (n = 108) were left untreated. In group II rejections (n = 186), the dose of oral corticosteroid therapy was increased, and in group III rejections (n = 6) major immunosuppressive treatment with methylprednisolone and antilymphocyte globulins (or Orthoclone OKT3) were initiated in view of the clinical and echocardiographic severity of the rejection. In the untreated group, 20 per cent of mild rejection progressed to moderate rejection, while 67 per cent are still at a mild stage in control myocardial biopsies. In group II, only 5 per cent of mild rejections have become moderate, and 19 per cent persisted as mild in control biopsies (p less than 0.05). The treatment of group III rejections resulted in complete disappearance of signs of heart failure and improvement of right and left ventricular contractile functions, proving that severe rejection was cured. This study demonstrates the effectiveness of increased oral corticosteroid therapy in minimal acute cardiac allograft rejections, without significant increase in infection or mortality rate. The principal reason for treating mild acute cardiac allograft rejections is to prevent their progression towards moderate rejections which require major immunosuppressive treatments and therefore have higher post-transplantation infection and mortality rates.