RESUMO
We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease-associated genes by a next-generation sequencing (NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1 (cytokine receptor-like factor 1). Mutations in CRLF1 have been associated with autosomal recessive Crisponi or cold-induced sweating syndrome type 1 (CS/CISS1), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC (p.Pro239Alafs*91) and the unaffected father carried the c.178T>A (p.Cys60Ser) variant. The c.713dupC variant has already been reported in affected CS/CISS1 patients, the pathogenicity of the c.178T>A variant was unclear. As reported previously for pathogenic CRLF1 variants, cytokine receptor-like factor 1 protein secretion from cells transfected with the c.178T>A variant was severely impaired. From these results we conclude that one should consider a CRLF1-related disorder in early onset achalasia even if other CS/CISS1 related symptoms are missing.
Assuntos
Anormalidades Múltiplas/genética , Acalasia Esofágica/genética , Deformidades Congênitas da Mão/genética , Hiperidrose/genética , Receptores de Citocinas/genética , Trismo/congênito , Anormalidades Múltiplas/fisiopatologia , Morte Súbita , Acalasia Esofágica/fisiopatologia , Fácies , Predisposição Genética para Doença , Deformidades Congênitas da Mão/fisiopatologia , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Hiperidrose/fisiopatologia , Mutação , Linhagem , Trismo/genética , Trismo/fisiopatologiaRESUMO
Posterior rib fractures are highly indicative of non-accidental trauma (NAT) in infants. Since 2000, the "two-thumbs" technique for cardiopulmonary resuscitation (CPR) of newborns and infants has been recommended by the American Heart Association (AHA). This technique is similar to the grip on an infant's thorax while shaking. Is it possible that posterior rib fractures in newborns and infants could be caused by the "two-thumbs" technique? Using computerized databases from three German children's hospitals, we identified all infants less than 12 months old who underwent professional CPR within a 10-year period. We included all infants with anterior-posterior chest radiographs taken after CPR. Exclusion criteria were sternotomy, osteopenia, various other bone diseases and NAT. The radiographs were independently reviewed by the Chief of Pediatric Radiology (MB) and a Senior Pediatrician, Head of the local Child Protection Team (IF). Eighty infants with 546 chest radiographs were identified, and 50 of those infants underwent CPR immediately after birth. Data concerning the length of CPR was available for 41 infants. The mean length of CPR was 11min (range: 1-180min, median: 3min). On average, there were seven radiographs per infant. A total of 39 infants had a follow-up radiograph after at least 10 days. No rib fracture was visible on any chest X-ray. The results of this study suggest rib fracture after the use of the "two-thumbs" CPR technique is uncommon. Thus, there should be careful consideration of abuse when these fractures are identified, regardless of whether CPR was performed and what technique used. The discovery of rib fractures in an infant who has undergone CPR without underlying bone disease or major trauma warrants a full child protection investigation.
Assuntos
Reanimação Cardiopulmonar/estatística & dados numéricos , Maus-Tratos Infantis/diagnóstico , Fraturas das Costelas/epidemiologia , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/métodos , Maus-Tratos Infantis/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Radiografia , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/etiologiaRESUMO
To date, the course of cognitive development in children after liver transplantation (Ltx) is poorly understood. Cognitive performance, however, is crucial in all developmental stages and for educational achievement. This cross-sectional single-center study examined the prevalence of long-term cognitive impairment in a cohort of 64 pediatric patients after Ltx. Median age at Ltx was 12 months. The revised Wechsler Intelligence Scale IV was administered to assess cognitive performance. Patients were compared with an age- and gender-matched group of children without a chronic health condition. Liver transplanted children performed significantly worse in three of four cognitive domains as well as in the Total Intelligence Quotient (Total IQ) (p = 0.017 to p = 0.005). Liver transplant recipients showed substantially more "serious delays" (IQ < 70) compared to the reference group (9.4% vs. 4.7%). Children with a genetic-metabolic disease performed worse than the other groups in three of the four WISC Indices and in the Total IQ (p = 0.05 to p = 0.01). The strongest association was revealed between height at Ltx and Verbal Comprehension (R(2) = 0.21), Perceptual Reasoning (R(2) = 0.30), Working Memory (R(2) = 0.23) and Total IQ (R(2) = 0.25). Our results indicate a high impact of primary diagnosis and height percentile at Ltx even on children's long-term cognitive performance.
Assuntos
Transtornos Cognitivos/etiologia , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/genética , Adolescente , Criança , Desenvolvimento Infantil , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Prognóstico , Fatores de RiscoRESUMO
Controlled trials of mTOR inhibitors in children following solid organ transplantation are scarce, although evidence from prospective single-arm studies is growing. Everolimus with reduced CNI therapy has been shown to be efficacious and safe in de novo pediatric kidney transplant patients in prospective trials. Prospective and retrospective data in children converted from CNI therapy to mTOR inhibition following kidney, liver, or heart transplantation suggest preservation of immunosuppressive efficacy. Good renal function has been maintained when mTOR inhibitors are used de novo in children following kidney transplantation or after conversion to mTOR inhibition with CNI minimization. mTOR inhibition with reduced CNI exposure is associated with a low risk for developing infection in children. Growth and development do not appear to be impaired during low-dose mTOR inhibition, but more studies are required. No firm conclusions can be drawn as to whether mTOR inhibitors should be discontinued in children requiring surgical intervention or whether mTOR inhibition delays progression of hepatic fibrosis after pediatric liver transplantation. In conclusion, current evidence suggests that use of mTOR inhibitors in children undergoing solid organ transplantation is efficacious and safe, but a number of issues remain unresolved and further studies are required.
Assuntos
Inibidores de Calcineurina , Transplante de Coração , Imunossupressores/administração & dosagem , Transplante de Rim , Transplante de Fígado , Serina-Treonina Quinases TOR/antagonistas & inibidores , Criança , Everolimo , Fibrose/patologia , Humanos , Fígado/patologia , Transtornos Linfoproliferativos/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Risco , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Resultado do Tratamento , CicatrizaçãoRESUMO
We report a case of a six-yr-old boy who developed chronic GVHD of the liver, intestines, and skin following allogeneic hematopoietic SCT. The boy received an allogeneic hematopoietic stem cell transplant at the age of two yr because of early recurrence of ALL. Chimerism analysis showed complete chimerism. In the following year, he developed GVHD despite adequate immunosuppressive therapy. Liver biopsy showed liver GVHD resulting in liver cirrhosis by the age of five yr. LTx was performed with a left liver lobe from the unrelated donor from whom the stem cells had been taken. Immunosuppressive therapy consisted of low-dose steroids and low-dose cyclosporine. The postoperative course was uneventful. Graft function was excellent, and we performed protocol biopsies at seven days and three wk as well as three, six, and nine months after transplantation; none of these showed any signs of rejection or GVHD. Immunosuppressive therapy was discontinued nine months after LTx. Three yr after transplantation, the boy is in good condition with normal graft function. To our knowledge, this is the first report on LTx following allogeneic hematopoietic SCT from the same unrelated living donor.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Falência Hepática/terapia , Transplante de Fígado/métodos , Transplante de Células-Tronco/métodos , Biópsia , Criança , Humanos , Imunossupressores/uso terapêutico , Falência Hepática/etiologia , Doadores Vivos , Masculino , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodosRESUMO
AIMS: We investigated interrelations between cognitive abilities, behavioural problems, quality of life and disease-related variables of children after LTX. METHODS: Our sample consisted of 25 children. They were 8.5/2.8 (M/SD) years old and had received the transplant 5.5/3.1 years previously. For assessment we used well-established instruments. RESULTS: Liver transplanted children scored below the population mean on the cognitive as well as on the behavioural instrument and showed scores below average in the scales Self-esteem, Friends and Total Score regarding QoL. Behavioural problems were associated with poorer cognitive performance (r=-0.38 to -0.63). QoL regarding physical well-being was correlated with sequential processing (r=0.41). Lower sequential processing scores were associated with lower QoL. Also between behavioural parameters and QoL correlations could be determined. Children with more behavioural problems experienced lower QoL (r=-0.40 to r=-0.76). Age at onset of disease showed correlations with behavioural and QoL parameters (r=-0.49 resp. r=0.44). Cognitive functioning was associated with medical complications (r=-0.44). CONCLUSIONS: High interrelations between cognitive functioning, behavioural deficits and QoL were obtained. Especially noticeable are correlations between sequential processing and internalized behavioural functions as both are associated with left lateralized brain functioning. This relationship could indicate differential effects on brain development during the preoperative phase.
Assuntos
Comportamento Infantil , Cognição , Transplante de Fígado/psicologia , Qualidade de Vida , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Portal vein thrombosis can occur as a result of primary anomalies, after liver transplantation, and for other reasons. It may result in severe complications secondary to portal hypertension, such as bleeding from esophageal or gastric varices, hypersplenism, or impaired somatic growth. In this retrospective study, we analyzed the outcome of 25 children who underwent a Rex shunt procedure. The following venous grafts were used as the shunt: the autologous internal or external jugular vein (n = 17) or a cryopreserved graft (n = 5); in three patients the umbilical vein was recanalized. The median follow up time was 109 months (range 18 days-146 months). The best results were achieved in patients in whom an autologous jugular vein segment was used as a vascular graft for the Rex shunt (shunt patency of 88%). In patients with a functioning shunt no further lower or upper gastrointestinal bleeding occurred. And in the entire study population hypersplenism syndrome improved after surgery. In our large cohort of pediatric patients, the Rex shunt has shown to be an effective method to eliminate portal hypertension and to revascularize the liver and thereby prevents the possible consequences of long-term portosystemic shunting.
Assuntos
Hipertensão Portal/terapia , Transplante de Fígado/métodos , Veia Porta/patologia , Trombose Venosa/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Criopreservação , Feminino , Humanos , Lactente , Masculino , Modelos Anatômicos , Derivação Portossistêmica Cirúrgica , Estudos Retrospectivos , Resultado do Tratamento , Veias Umbilicais/patologiaRESUMO
UNLABELLED: We report on two brothers with hyperimmunoglobulinemia D (patient 1: serum immunoglobulin D [IgD] concentration initially 61 IU/ml, later on 340 IU/ml; patient 2: serum IgD concentration 144 IU/ml; normal <100 IU/ml, 97th centile) and periodic fever syndrome (HIDS). Both are compound heterozygous for the mevalonate kinase (MVK) mutations V377I and I268T. They developed significant B cell cytopenia (7%, 129/microl and 11%, 132/microl, respectively; normal ranges 12-22%, 300-500/microl) with hypogammaglobulinemia (IgG 5.48 g/l and IgG 5.22 g/l, respectively; normal range IgG 6-13 g/l). Furthermore, the clinical spectrum shows an interesting atypical autoinflammatory symptomatology. The therapy consisted of prednisone, azathioprine, and intravenous immunoglobulins (IVIG), which results in reduced incidence and severity of febrile attacks. CONCLUSION: The pathogenesis and clinical presentation of HIDS is still not fully understood and show a great variability. To our knowledge, severe B cell cytopenia in children with HIDS has not been reported before. Furthermore, the therapy of febrile episodes is still performed on an individual basis in affected patients.
Assuntos
Linfócitos B , Febre , Imunoglobulina D/sangue , Linfopenia , Deficiência de Mevalonato Quinase , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Agamaglobulinemia/sangue , Azatioprina/uso terapêutico , Criança , Febre/sangue , Febre/tratamento farmacológico , Febre/genética , Glucocorticoides/uso terapêutico , Heterozigoto , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lactente , Linfopenia/sangue , Linfopenia/tratamento farmacológico , Linfopenia/genética , Linfopenia/fisiopatologia , Masculino , Deficiência de Mevalonato Quinase/sangue , Deficiência de Mevalonato Quinase/tratamento farmacológico , Deficiência de Mevalonato Quinase/genética , Deficiência de Mevalonato Quinase/fisiopatologia , Mutação , Periodicidade , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Prednisona/uso terapêutico , Irmãos , SíndromeRESUMO
OBJECTIVE: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes. PATIENTS AND METHODS: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes. RESULTS: 174 HIV- infected paediatric patients were followed up in 12 centres in Germany and Austria between 1998 and 2003. Initially 54 (31%) patients had no antiretroviral therapy, 35 (20%) received a two-drug regimen (ART) and 85 patients (49%) a highly active antiretroviral therapy (HAART>or=3 drugs). After an observation period of 5 years, 8 patients (4%) had no therapy, 17 (10%) were on ART and 134 patients on HAART (77%). The number of patients with salvage therapy (>or=4 drugs) increased from 5 (3%) to 15 patients (9%). 72 of 166 treated patients (43%) had no change of their drug regimes, 68 patients (41%) had one change and 26 patients (16%)>or=2 changes. Main reasons for changes were increased viral load (49%), immunologic deterioration (21%) and adverse events (14%). During the follow up period no patient died. According to the CDC classification, disease progression was seen in 48 of 174 patients (28%), of whom 20 had deteriorations of clinical categories (A, B, C) and 28 of immunologic categories. Using Kaplan-Meier curves, the mean time from study onset until change of clinical categories was 61 months for patients on HAART, 26 months for patients on ART and 14 months for patients without ART. CONCLUSION: In paediatric patients with HIV infection, disease progression has declined substantially by introduction of HAART. Superiority of HAART compared with ART was demonstrated. Non-adherence as well as other reasons for treatment failure have to be studied more carefully.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Antirretrovirais/farmacologia , Terapia Antirretroviral de Alta Atividade , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Alemanha , Infecções por HIV/patologia , Humanos , Lactente , Masculino , Adesão à Medicação , Estados UnidosRESUMO
End-stage liver cirrhosis because of metabolic or infectious diseases predisposes to hepatic malignancies like hepatocellular carcinoma. We report the first case of hepatoblastoma incidentally detected in the explanted liver of a 2-yr-old child undergoing liver transplantation for cirrhosis because of progressive familial intrahepatic cholestasis (PFIC). The diagnosis was difficult to obtain. The hepatoblastoma was not seen on ultrasound examination of the cirrhotic liver. As we could confirm retrospectively, alpha fetoprotein (AFP) was found elevated prior to transplantation. Two years after successful transplantation, there are no signs of malignancy detectable by clinical and radiological methods. We conclude from this case that PFIC may induce hepatoblastoma and that children with liver cirrhosis should undergo routine screening of serum AFP concentration.
Assuntos
Colestase Intra-Hepática/fisiopatologia , Hepatoblastoma/patologia , Hepatócitos/patologia , Neoplasias Hepáticas/patologia , Transplante de Fígado , Pré-Escolar , Colestase Intra-Hepática/patologia , Consanguinidade , Feminino , Hepatoblastoma/cirurgia , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Resultado do TratamentoRESUMO
Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.
Assuntos
Agamaglobulinemia/etiologia , Transplante de Fígado/efeitos adversos , Agamaglobulinemia/tratamento farmacológico , Agamaglobulinemia/imunologia , Atresia Biliar/cirurgia , Criança , Imunodeficiência de Variável Comum/etiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Falência Hepática Aguda/cirurgia , Subpopulações de LinfócitosRESUMO
The technique of liver splitting offers an effective way of increasing the donor pool and decreasing pediatric waiting list mortality. A donor liver is divided in such a way that the left lateral liver graft can be transplanted into a small child and the right extended liver graft into an adult. This innovative technique did not harm the adult recipient pool. Because of its technical complexity and the initial poor results after split liver transplantation (SLT) this procedure has slowly gained acceptance in the Transplantation Community after its first introduction in 1988 (4). Small children with end stage liver disease suffered the most from the extreme shortage of cadaveric donor organs due to the difficulty of finding size-matched donors. The successful surgical development of SLT and a better donor and recipient selection have led to a reduction of the pediatric pretransplant mortality to nearly zero and to results comparable with those after whole organ transplantation (WLT). By splitting a donor organ into two 'full' hemi-grafts and providing a small adult ( < 60 kg) or a big child ( > 30 kg) with the full left graft and a medium-sized adult (60-80 kg) with the full right graft, a small-for-size situation for adolescents or adults can be avoided and the total number of available grafts can be increased. It is the goal to provide each recipient with its customized graft in the near future. However, splitting for two adults requires high technical skills and profound knowledge of the anatomic variations and should be performed in centers with large transplantation experience.
Assuntos
Transplante de Fígado/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/tendências , Masculino , Estudos RetrospectivosRESUMO
The chimeric, monoclonal antibody basiliximab inhibits the proliferation and clonal expansion of activated T cells. To date basiliximab has been used only in combination with other immunosuppressive agents for rejection prophylaxis after solid organ transplantation. An infant underwent liver transplantion (LTx) at the age of 5 months because of biliary atresia. The primary immunosuppression consisted of cyclosporine and prednisolone. As a result of a steroid resistant rejection episode on day 26 post-LTx we had to switch the initial immunosuppressive regiment to tacrolimus and steroids. Because of severe cholestasis and assumed impaired enteral resorption we were forced to administer an unusually high dosage (2 mg/kg/day) of tacrolimus. Four months after LTx an intestinal B-cell lymphoma was diagnosed when the patient suffered from a small bowel perforation. After stopping the immunosuppressive medication we started treatment with the anti-CD20 monoclonal antibody rituximab for B-cell depletion. During the 12 wk no B cells were detectable in the peripheral blood by flow cytometry. In this setting we started a monotherapy with repetitive doses of basiliximab for immunosuppression. During the following course there was no further rejection and no recurrence of the tumor. From this experience we conclude that monotherapy with basiliximab after LTx and anti-CD20 treatment for B-cell lymphoma is efficient and safe.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Fígado/efeitos adversos , Linfoma de Células B/tratamento farmacológico , Proteínas Recombinantes de Fusão , Anticorpos Monoclonais Murinos , Basiliximab , Humanos , Lactente , Transplante de Fígado/imunologia , Linfoma de Células B/etiologia , Masculino , Rituximab , Resultado do TratamentoRESUMO
BACKGROUND: Data on the oxidative metabolism of polymorphonuclear neutrophils (PMN) after solid organ transplantation are very limited. We hypothesized that immunosuppressive agents reduce the capacity of PMN to produce reactive oxygen species, such as O2(-), H2O2, OH, and OCL(-) leading to an increased susceptibility to infectious complications after liver transplantation. METHODS: A lucigenin-enhanced chemiluminescence (CL) assay was used with soluble and particulate stimuli to study the oxidative metabolism of PMN in pediatric liver graft recipients. Sixteen patients (median age: 2.4 yr) were enrolled in a prospective study and integrated CL response was compared with the CL activity of 29 healthy controls. RESULTS: In the second week post-transplant, we found a significantly reduced CL activity. Pre-operatively, and after lowering steroids and cyclosporin A (CsA) the oxidative burst was normal. CONCLUSIONS: Our data suggest that CsA and steroids may not only influence T and B cells but also PMN, which may be a relevant factor for the incidence of infectious complications in pediatric liver graft recipients.
Assuntos
Transplante de Fígado/fisiologia , Neutrófilos/fisiologia , Explosão Respiratória/fisiologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Medições Luminescentes , Estudos ProspectivosAssuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Proteínas Recombinantes de Fusão , Doença Aguda , Anticorpos Monoclonais/efeitos adversos , Basiliximab , Peso Corporal , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Quimioterapia Combinada , Rejeição de Enxerto/patologia , Humanos , Hipertensão/epidemiologia , Imunossupressores/efeitos adversos , Lactente , Rim/efeitos dos fármacos , Rim/patologia , Complicações Pós-Operatórias/epidemiologia , Prednisolona/uso terapêuticoAssuntos
Síndrome de Alagille/cirurgia , Transplante de Fígado/métodos , Adolescente , Síndrome de Alagille/fisiopatologia , Aorta Torácica/anormalidades , Criança , Pré-Escolar , Colesterol/sangue , Humanos , Testes de Função Renal , Transplante de Fígado/fisiologia , Obstrução da Artéria Renal/fisiopatologiaRESUMO
OBJECTIVE: To assess and compare the value of split-liver transplantation (SLT) and living-related liver transplantation (LRT). SUMMARY BACKGROUND DATA: The concept of SLT results from the development of reduced-size transplantation. A further development of SLT, the in situ split technique, is derived from LRT, which itself marks the optimized outcome in terms of postoperative graft function and survival. The combination of SLT and LRT has abolished deaths on the waiting list, thus raising the question whether living donor liver transplantation is still necessary. METHODS: Outcomes and postoperative liver function of 43 primary LRT patients were compared with those of 49 primary SLT patients (14 ex situ, 35 in situ) with known graft weight performed between April 1996 and December 2000. Survival rates were analyzed using the Kaplan-Meier method. RESULTS: After a median follow-up of 35 months, actual patient survival rates were 82% in the SLT group and 88% in the LRT group. Actual graft survival rates were 76% and 81%, respectively. The incidence of primary nonfunction was 12% in the SLT group and 2.3% in the LRT group. Liver function parameters (prothrombin time, factor V, bilirubin clearance) and surgical complication rates did not differ significantly. In the SLT group, mean cold ischemic time was longer than in the LRT group. Serum values of alanine aminotransferase during the first postoperative week were significantly higher in the SLT group. In the LRT group, there were more grafts with signs of fatty degeneration than in the SLT group. CONCLUSIONS: The short- and long-term outcomes after LRT and SLT did not differ significantly. To avoid the risk for the donor in LRT, SLT represents the first-line therapy in pediatric liver transplantation in countries where cadaveric organs are available. LRT provides a solution for urgent cases in which a cadaveric graft cannot be found in time or if the choice of the optimal time point for transplantation is vital.
Assuntos
Transplante de Fígado , Doadores Vivos , Adolescente , Criança , Pré-Escolar , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Lactente , Fígado/irrigação sanguínea , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Complicações Pós-Operatórias , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Taxa de SobrevidaRESUMO
Several studies have shown a significant reduction of acute cellular graft rejection in adult liver and kidney graft recipients treated with monoclonal anti-interleukin-2 (IL-2)-receptor antibodies. The mechanism was inhibition of activated T-helper cells by blocking the alpha-chain (CD25) of the IL-2 receptor. The pilot study described here evaluated the use of basiliximab in pediatric liver transplantation (LTx), which is the first report on its use in children. Fifty-two liver-transplanted children were analyzed in this study. A matched-pair historical control group (n = 26) received cyclosporin A (CsA) and prednisolone, and patients in the basiliximab group (n = 26) were treated with low-dose CsA and basiliximab (after reperfusion and on day 4 post-transplant). The incidences were compared of acute graft rejections, infectious complications, and the adverse effects of immunosuppressive medication within the first 6 months post-transplant. The incidence of acute rejection was significantly higher in the control group (61.5% vs. 11.5%, p = 0.0004). The frequency of infectious complications was similar (46.1% vs. 53.8%). Patients in the basiliximab group showed less arterial hypertension; however, the differences were not statistically significant (30.7% vs. 7.7%, p = 0.07). Nephrotoxicity, hepatotoxicity or neurotoxicity were only seen in the control group (7.7%; 3.8%; 3.8%, respectively). Hence, the use of basiliximab in combination with CsA and steroids in pediatric liver transplant recipients is safe and reduces the incidence of acute graft rejection. Further studies are needed to confirm our preliminary results and to analyze long-term effects on post-transplant lymphoproliferative disease, chronic rejection, and patient survival.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Ciclosporina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Fígado/imunologia , Proteínas Recombinantes de Fusão , Basiliximab , Criança , Ciclosporina/sangue , Feminino , Humanos , Masculino , Projetos Piloto , Estudos RetrospectivosRESUMO
BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.