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1.
Ann Surg ; 267(3): 419-425, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28885508

RESUMO

: This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients. OBJECTIVE: To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups. BACKGROUND: Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative. METHODS: Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff. RESULTS: Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.


Assuntos
Benchmarking , Transplante de Fígado/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Feminino , Humanos , Masculino , Análise de Sobrevida
2.
Clin Transplant ; 32(3): e13205, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29345754

RESUMO

INTRODUCTION: Full-split liver transplantation (LTX) offers the possibility to expand the donor pool by utilization of one liver for two adults. The aim of our study was to analyze the long-term outcome in a large series and its applicability in the recent transplant era. METHODS: We performed a retrospective analysis of all full-split LTX from deceased donors (1999-2015). Additionally, the potential of full-split LTX was retrospectively analyzed in all whole organ LTX recipients between 2006 and 2015 (after introduction of the MELD allocation). RESULTS: We performed 44 full-split LTX, thereof 82% before introduction of the MELD-based allocation system in Germany. Analysis showed highly selected recipients (median MELD score 8 points) and organ data (median donor age 30 years). 5- and 10-year patient survival rates after full-left and full-right LTX were 90.7%/90.7% and 85.2%/56.8% (P = .301), corresponding graft survival rates were 80.5%/80.5% in full-left grafts and 73.7%/36.8% in full-right graft (P = .198). CONCLUSION: In the past, in case of strict donor and recipient selection, full-split LTX was a feasible method with a good outcome. Due to introduction of the national waiting list with a patient-oriented allocation based on the MELD score in 2006, full-split LTX seems to be not any longer applicable.


Assuntos
Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/mortalidade , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Listas de Espera , Adulto Jovem
3.
Pediatr Transplant ; 21(6)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28580726

RESUMO

The enzymatic defect in MSUD results in accumulation of neurotoxic metabolites of BCAAs. LTX has shown to be a feasible strategy in patients non-responsive to diet. Because of sufficient enzyme activity in extrahepatic tissues in healthy people, the MSUD liver graft is a suitable domino organ. We present the first case of a technical challenging ex situ split of a MSUD domino organ transplanted into two pediatric recipients. The domino graft donor was a 21-year-old female (58 kg) suffering from MSUD with recurrent metabolic decompensation despite strict diet. The organ was allocated to a 14-year-old girl (55 kg) with primary sclerosing cholangitis. Due to excellent organ quality and suitable anatomy, a backward split for a girl of 3 months (5 kg) with decompensated liver cirrhosis due to biliary atresia was performed. The postoperative course was without relevant complications, and the three recipients were discharged on postoperative days 28, 29, and 45, respectively, with good organ function. BCAAs in plasma were normal in the two domino graft recipients, and the MSUD patient showed mildly elevated but stable BCAA concentrations despite an unrestricted diet. Split-domino LTX enabled successful transplantation of three patients of the waiting list with only one deceased donor graft.


Assuntos
Atresia Biliar/complicações , Colangite Esclerosante/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Doença da Urina de Xarope de Bordo/cirurgia , Adolescente , Feminino , Humanos , Lactente , Cirrose Hepática/etiologia , Adulto Jovem
4.
Transpl Infect Dis ; 18(6): 850-855, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639176

RESUMO

BACKGROUND: BK polyomavirus (BKV) infection and BKV nephropathy (BKVN) are risk factors for allograft function and survival. METHODS: We retrospectively analyzed BK viremia and BKVN in 348 patients who received a kidney transplantation donated after brain death (n=232) or living donation (n=116) between 2008 and 2013. A total of 266 patients were treated with standard immunosuppression consisting of basiliximab induction, calcineurin inhibitor (CNI), and mycophenolic acid (MPA, n=219) or everolimus (n=47); 82 patients received more intense immunosuppression with lymphocyte depletion, CNI and MPA (n=38) or everolimus (n=44). RESULTS: BK viremia occurred in 33 (9.5%) patients in the first year and in 7 (2.0%) recipients in the second year after transplantation. BKVN occurred in 4 (1.1%) patients in the first year. Donor and recipient age, diabetes, previous transplantation, and type of transplantation (donated after brain death vs living donation) were not risk factors (P>.05). BK incidence did not differ depending on induction or maintenance immunosuppression. CONCLUSION: Incidence of BK viremia is independent of recipient characteristics, type of transplantation as well as induction and maintenance immunosuppression.


Assuntos
Vírus BK/efeitos dos fármacos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Nefropatias/epidemiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Viremia/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Vírus BK/isolamento & purificação , Basiliximab , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Feminino , Alemanha/epidemiologia , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Nefropatias/virologia , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Infecções por Polyomavirus/virologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/virologia , Viremia/virologia
5.
Clin Transplant ; 29(11): 1021-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333844

RESUMO

ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low-dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three-yr follow-up treated with this regimen. Three-yr patient survival and graft survival were 96% and 83%. The rate of acute T-cell-mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor-based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Serina-Treonina Quinases TOR/antagonistas & inibidores , Everolimo/uso terapêutico , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Testes de Função Renal , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Tacrolimo/uso terapêutico
6.
Ther Drug Monit ; 37(4): 539-45, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25525763

RESUMO

BACKGROUND: Early detection of alcohol misuse in orthotopic liver transplantation recipients is essential to offer patients support and prevent organ damage. Here, ethyl glucuronide, a metabolite of ethanol found in hair (hEtG), was evaluated for detection of alcohol consumption. METHODS: In 104 transplant recipients, 31 with underlying alcoholic liver disease (ALD) and 73 with non-ALD, hEtG was determined in addition to the alcohol markers urine EtG, blood ethanol, methanol, and carbohydrate-deficient transferrin. Results were compared with patients' self-reports in a questionnaire and with physicians' assessments. RESULTS: By physicians' assessments, 22% of the patients were suspected of consuming alcohol regularly, although only 6% of the patients acknowledged consumption of a moderate or high amount of alcohol. By testing all markers except for hEtG, alcohol consumption was detected in 7% of the patients. When hEtG testing was added to the assessment, consumption was detected in 17% of the patients. Hair-EtG determination alone revealed chronic alcohol consumption of >10 g/d in 15% of the patients. ALD patients had a positive hEtG result significantly more often than non-ALD patients did (32% versus 8%; P = 0.003). Also, the concentration of hEtG was higher in ALD patients (P = 0.049) and revealed alcohol abuse with consumption of >60 g ethanol per day in 23% of ALD and 3% of non-ALD patients. Patients' self-reports and physicians' assessments had a low sensitivity of 27% and 67%, respectively, for detecting regular alcohol intake as indicated by hEtG. CONCLUSIONS: Hair-EtG determination improved the detection of liver transplant patients who used alcohol, and revealed regular alcohol consumption in 32% of ALD and 8% of non-ALD patients.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Glucuronatos/análise , Cabelo/química , Transplante de Fígado/métodos , Detecção do Abuso de Substâncias/métodos , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Etanol/sangue , Feminino , Glucuronatos/urina , Humanos , Masculino , Metanol/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Transferrina/análogos & derivados , Transferrina/metabolismo
7.
Liver Int ; 34(3): 469-76, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23829409

RESUMO

BACKGROUND & AIMS: Prior to listing patients for Orthotopic liver transplantation (OLT) an abstention period of 6 months is required. Ethyl glucuronide in the hair is a new reliable marker for the assessment of alcohol consumption. Here, the diagnostic value of determining the ethyl glucuronide concentration in the hair of liver transplant candidates was evaluated. METHODS: In 63 transplant candidates with alcoholic liver cirrhosis and 25 control patients with cirrhosis of other aetiologies alcohol markers, i.e. hEtG, urine EtG, blood ethanol, methanol and carbohydrate deficient transferrin were determined in parallel to an interview with a psychologist. RESULTS: A total of 19 (30%) transplant candidates admitted alcohol consumption within the last 6 months, while 39/63 (62%) were positive for at least one alcohol marker. In 52% of the 44 candidates denying alcohol consumption, abstention was disproved by detecting at least one positive alcohol marker, in 83% of cases by a positive hEtG result. In the control patients stating abstention from alcohol all hEtG tests were negative. No impact of renal or liver function on hEtG results was detected. A specificity of 98% and a positive predictive value of 92% were calculated for testing hEtG in proximal hair segment and applying a cut-off of 30 pg/mg. CONCLUSIONS: In 52% of patients denying alcohol consumption within the last 6 months, alcohol abstention was disproved, in 83% of cases by hEtG testing. Therefore, hEtG is a promising new marker for the evaluation of long-term alcohol abstention in liver transplant candidates.


Assuntos
Abstinência de Álcool , Glucuronatos/química , Cabelo/química , Cirrose Hepática Alcoólica/diagnóstico , Transplante de Fígado , Adulto , Consumo de Bebidas Alcoólicas , Biomarcadores , Etanol/sangue , Etanol/química , Feminino , Humanos , Masculino , Metanol/sangue , Metanol/química , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Transferrina/análogos & derivados , Transferrina/química
8.
Pediatr Transplant ; 18(4): 377-84, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24802344

RESUMO

In case of graft failure, re-LTX is the only life-saving option but it has been associated with inferior results. This study analyzes the outcome following pediatric re-LTX with a main focus on the timely relation between initial transplant and re-LTX. All pediatric LTX at our institution between 2000 and 2010 divided into patients with primary LTX and patients undergoing re-LTX early (≤30 days) or late (>30 days) after previous LTX were analyzed. Two hundred and ninety-eight primary LTX(79%), 33 early (9%), and 46 late (12%) re-LTX were performed. Patient/graft survival was significantly worse for children undergoing early re-LTX compared to primary LTX and late re-LTX (p = 0.024/0.001 and p = 0.015/0.03). One-/five-yr graft survival rates were 66%/49% for early re-LTX compared to 86%/76% for late re-LTX and 90%/74% for primary LTX. The inferior results in children undergoing early re-LTX were due to events occurring in the first six months with similar survival thereafter. No difference in outcome was evident after adjustment of the groups for high-urgency status. Outcome was excellent for primary LTX and late re-LTX, supporting late re-LTX in children. Early re-LTX takes an elevated risk of early graft loss and patient death; however, beyond the early postoperative period, the outcome was comparable.


Assuntos
Sobrevivência de Enxerto , Transplante de Fígado/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Transplante de Fígado/métodos , Masculino , Avaliação de Resultados da Assistência ao Paciente , Reoperação/métodos , Reoperação/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
10.
Transpl Int ; 26(12): 1217-24, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24118382

RESUMO

Due to a lack of available size-matched liver grafts from children, most pediatric recipients are transplanted with technical variant grafts from adult donors. Size requirements for these grafts are not well defined, and consequences of mismatched graft sizes in pediatric liver transplantation are not known. Existing formulas for calculation of a standard liver volume are mostly derived from adults disregarding the age-related percentual liver weight changes in children. In this study, we aimed to establish a formula for general use in children to calculate the standard liver volume. In a second step, the formula was applied in pediatric patients undergoing liver transplantation at our institution between 2000 and 2010 (n = 377). Analysis of a large number (n = 388) of autopsy data from children by regression analysis revealed a best fit for two formulas: "Formula 1," children 0 to ≤1 year (n = 246): standard liver volume [ml] = -143.062973 +4.274603051 * body length [cm] + 14.78817631 * body weight [kg]; "Formula 2," children >1 to <16 years (n = 142): standard liver volume [ml] = -20.2472281 + 3.339056437 * body length [cm] + 13.11312561 * body weight [kg]. In comparison with children receiving size-matched organs, we found an elevated risk of liver graft failure in children transplanted with a small-for-size graft, whereas large-for-size organs seem to have no negative impact.


Assuntos
Transplante de Fígado/métodos , Fígado/anatomia & histologia , Adolescente , Autopsia , Peso Corporal , Criança , Pré-Escolar , Função Retardada do Enxerto , Sobrevivência de Enxerto , Humanos , Lactente , Fígado/crescimento & desenvolvimento , Tamanho do Órgão
11.
Transpl Int ; 26(6): 640-50, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23582048

RESUMO

In ARPKD, mutations in the PKHD1 gene lead to remodeling of the kidneys and liver. These may result in progressive liver fibrosis with portal hypertension requiring combined liver and kidney transplantation (CLKT). There is currently no consensus on the indication for CLKT and data on long-term outcomes are scarce. We analyzed in detail the pretransplant liver symptomatology, laboratory and ultrasound data, histological studies, and genotypes in eight patients undergoing CLKT. The median age was 10.1 years (range 1.7-16) and median follow-up was 4.6 years (range 1.1-8.9). All patients had clinical signs of portal hypertension and abnormal ultrasound findings. Congenital hepatic fibrosis was present in all pretransplant biopsies (6 out of 8 patients) and in all explanted livers. All patients survived; liver and kidney graft survival was 72% and 88%, respectively. Liver and kidney function were stable in all patients with a median eGFR of 70 ml/min/1.73 m² (range 45-108 ml/min/1.73 m²). Height-SDS improved significantly after 12, 24, and 36 months (P = 0.016, 0.022 and 0.018 respectively). The indication for CLKT remains challenging and controversial. A favorable outcome for patients with ARPKD can be achieved by using the degree of portal hypertension, longitudinal ultrasound examinations, and preoperative liver histology as parameters for CLKT.


Assuntos
Transplante de Rim , Transplante de Fígado , Fígado/patologia , Rim Policístico Autossômico Recessivo/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Hipertensão Portal/patologia , Hipertensão Portal/cirurgia , Lactente , Falência Renal Crônica/patologia , Falência Renal Crônica/cirurgia , Fígado/diagnóstico por imagem , Cirrose Hepática/patologia , Masculino , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/patologia , Receptores de Superfície Celular/genética , Estudos Retrospectivos , Ultrassonografia
12.
Pediatr Transplant ; 17(8): 757-64, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24164827

RESUMO

Individualization of immunosuppressive medications is an important objective in transplantation medicine. Reliable biomarkers to distinguish between patients dependent from intensive immunosuppressive therapy and those where therapy can be minimized among pediatric transplant recipients receiving immunosuppressive medications are still not established. We evaluated the potential of cross-sectional quantification of regulatory T cells, lymphocyte subsets, and cytokine concentrations as biomarkers in 60 pediatric liver transplant recipients with AR, CR, or normal graft function and in 11 non-transplanted patients. Transplant recipients presenting with AR had significantly higher CD8+ T-cell counts, significantly higher concentrations of IL-2, and increased levels of IFN-γ compared with asymptomatic patients or controls. Regulatory T-cell numbers did not differ between children with rejection and children with good graft function. A tendency toward increased concentrations of IL-4 and TGF-ß was detected in transplant recipients with good graft function. Cross-sectional parameters of peripheral regulatory T cells in pediatric liver transplant recipients do not seem to be valuable biomarkers for individualizing immunosuppressive therapy prior to the weaning process. Lymphocyte subsets, IL-2, IFN-γ, IL-4, and TGF-ß serum concentrations may be helpful to identify children in whom immunosuppression can be reduced or discontinued.


Assuntos
Biomarcadores/sangue , Transplante de Fígado , Linfócitos T Reguladores/citologia , Adolescente , Linfócitos T CD8-Positivos/citologia , Separação Celular , Criança , Pré-Escolar , Estudos Transversais , Feminino , Citometria de Fluxo , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Lactente , Interferon gama/sangue , Interleucina-2/sangue , Interleucina-4/sangue , Transplante de Rim , Masculino , Tacrolimo/uso terapêutico , Fator de Crescimento Transformador beta/sangue
13.
Hepatology ; 54(5): 1640-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21809364

RESUMO

UNLABELLED: Optimal selection of liver transplant candidates and early detection of alcohol relapse after orthotopic liver transplantation (OLT) is necessary to improve long-term outcomes. In this study, urinary ethyl glucuronide (uEtG) was prospectively evaluated as a novel screening tool for alcohol detection in the transplant setting. Overall, 141 liver transplant candidates and recipients, visiting the outpatient clinic for a total of 308 times, were included. At each visit, the alcohol markers, uEtG, ethanol, methanol, and carbohydrate-deficient transferrin (CDT), as well as the state markers, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV), were determined, then compared to patients' self-reports on alcohol intake. Urinary EtG significantly increased the detection rate of alcohol consumption, compared to the other alcohol markers (P < 0.001). In 93% of patients and at 92.5% of visits with positive alcohol markers, alcohol intake was detected by uEtG and/or CDT. Sensitivity and specificity of uEtG were 89.3% and 98.9% and of CDT were 25% and 98.6%, respectively. Urinary EtG was the best independent predictor of alcohol consumption in univariate and multivariate analysis (positive predictive value: 89.3%; negative predictive value: 98.9%; odds ratio: 761.1; P < 0.001). It showed a superior prediction rate, when compared to established alcohol and state markers, as well as to the combination of CDT with MCV and GGT, assessed by net reclassification improvement (NRI) (NRI: 1.01, P < 0.001; NRI: 1.755, P < 0.001). CONCLUSION: uEtG is a sensitive, specific, and reliable marker for the detection of recent alcohol intake pre- and post-OLT. In combination with CDT, uEtG should be considered as a tool for routine alcohol screening within the transplant setting.


Assuntos
Consumo de Bebidas Alcoólicas/urina , Glucuronatos/urina , Hepatopatias Alcoólicas , Transplante de Fígado , Programas de Rastreamento/métodos , Temperança , Adulto , Idoso , Feminino , Humanos , Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/cirurgia , Hepatopatias Alcoólicas/urina , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Prevenção Secundária , Sensibilidade e Especificidade , Listas de Espera , Adulto Jovem
14.
Transpl Int ; 25(11): 1158-64, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22882364

RESUMO

Treatment options of recurrent hepatocellular carcinoma (HCC) after liver transplantation are limited and data on systemic compounds for advanced tumor stages in transplant recipients are sparse. We retrospectively analyzed the toxicity, tolerability, and efficacy of sorafenib in combination with mTOR inhibitors (mTORi), or calcineurin inhibitors (CNI) in transplant recipients with recurrent HCC. In total, 20 of 92 patients transplanted for HCC within a 10-year time period, experienced tumor recurrence. In case of ineligibility for other treatment options, patients received sorafenib (n = 13). In addition, CNI were stopped and switched to mTORi in nine patients, whereas CNI were continued in four patients. Grade 3-4 adverse events were observed in 92% of all patients necessitating sorafenib discontinuation in 77%. The most common severe adverse events were acute hepatitis, diarrhea, hand-foot - skin reaction and bone marrow suppression. In patients receiving sorafenib/mTORi one patient achieved partial response, and four achieved stable disease. In this cohort of liver transplant recipients side effects prevented full dosing of sorafenib and necessitated discontinuation of sorafenib in the majority of patients, yet antitumor efficacy seemed promising in combination with mTORi.


Assuntos
Antineoplásicos/efeitos adversos , Benzenossulfonatos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piridinas/efeitos adversos , Adulto , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Inibidores de Calcineurina , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Transplante de Fígado , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/efeitos adversos , Recidiva , Estudos Retrospectivos , Sorafenibe , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resultado do Tratamento
15.
Front Pharmacol ; 13: 1009612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267268

RESUMO

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

17.
Liver Transpl ; 17(2): 104-14, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21280182

RESUMO

Liver transplantation is an established treatment for acute and chronic liver disease. However, because of the shortage of donor organs, it does not fulfill the needs of all patients. Hepatocyte transplantation is promising as an alternative method for the treatment of end-stage liver disease and as bridging therapy until liver transplantation. Our group has been working on the optimization of matrix-based hepatocyte transplantation. In order to increase cell survival after transplantation, freshly isolated human hepatocytes were seeded onto biodegradable poly(l-lactic acid) (PLLA) polymer scaffolds and were cultured in a flow bioreactor. PLLA discs were seeded with human hepatocytes and exposed to a recirculated medium flow for 6 days. Human hepatocytes formed spheroidal aggregates with a liver-like morphology and active metabolic function. Phase contrast microscopy showed increasing numbers of spheroids of increasing diameter during the culture period. Hematoxylin and eosin histology showed viable and intact hepatocytes inside the spheroids. Immunohistochemistry confirmed sustained hepatocyte function and a preserved hepatocyte-specific cytoskeleton. Albumin, alpha-1-antitrypsin, and urea assays showed continued production during the culture period. Northern blot analysis demonstrated increasing albumin signals. Scanning electron micrographs showed hepatocyte spheroids with relatively smooth undulating surfaces and numerous microvilli. Transmission electron micrographs revealed intact hepatocytes and junctional complexes with coated pits and vesicles inside the spheroids. Therefore, we conclude that primary human hepatocytes, precultured in a flow bioreactor on a PLLA scaffold, reorganize to form morphologically intact liver neotissue, and this might offer an optimized method for hepatocyte transplantation because of the expected reduction of the initial cell loss, the high regenerative potential in vivo, and the preformed functional integrity.


Assuntos
Implantes Absorvíveis , Hepatócitos/transplante , Ácido Láctico , Regeneração Hepática , Polímeros , Engenharia Tecidual/métodos , Alicerces Teciduais , Biomarcadores/metabolismo , Reatores Biológicos , Northern Blotting , Separação Celular , Forma Celular , Sobrevivência Celular , Células Cultivadas , Imunofluorescência , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Humanos , Imuno-Histoquímica , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Poliésteres , Albumina Sérica/genética , Albumina Sérica/metabolismo , Fatores de Tempo , Ureia/metabolismo , alfa 1-Antitripsina/metabolismo
18.
Biotechnol Bioeng ; 108(1): 141-50, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20824672

RESUMO

Primary rat hepatocytes are a widely used experimental model to estimate drug metabolism and toxicity. In currently used two-dimensional (2D) cell culture systems, typical problems like morphological changes and the loss of liver cell-specific functions occur. We hypothesize that the use of polymer scaffolds could overcome these problems and support the establishment of three-dimensional (3D) culture systems in pharmaceutical research. Isolated primary rat hepatocytes were cultured on collagen-coated nanofibrous scaffolds for 7 days. Cell loading efficiency was quantified via DNA content measurement. Cell viability and presence of liver-cell-specific functions (albumin secretion, glycogen storage capacity) were evaluated. The activity of liver-specific factors was analyzed by immunofluorescent staining. RNA was isolated to establish quantitative real-time PCR. Our results indicate that primary rat hepatocytes cultured on nanofibrous scaffolds revealed high viability and well-preserved glycogen storage. Albumin secretion was existent during the entire culture period. Hepatocytes remain HNF-4 positive, indicating highly preserved cell differentiation. Aggregated hepatocytes re-established positive signaling for Connexin 32, a marker for differentiated hepatocyte interaction. ZO-1-positive hepatocytes were detected indicating formation of tight junctions. Expression of cytochrome isoenzymes was inducible. Altogether the data suggest that nanofibrous scaffolds provide a good in vitro microenvironment for neo tissue regeneration of primary rat hepatocytes.


Assuntos
Hepatócitos/fisiologia , Fígado Artificial , Polímeros , Alicerces Teciduais , Animais , Sobrevivência Celular , Células Cultivadas , Nanofibras , Técnicas de Cultura de Órgãos , Farmacologia/métodos , Ratos , Engenharia Tecidual/métodos , Toxicologia/métodos
19.
Transpl Int ; 24(6): 610-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21401730

RESUMO

Nowadays, most paediatric liver transplant recipients receive a split or other technical variant graft from adult deceased or live donors, because of a lack of available age- and size matched paediatric donors. Few data are available, especially for liver grafts obtained from very young children (<6 years). We analysed all paediatric liver transplantations between 1989 and 2009. Recipients were divided into five groups (1-5) depending on donor age (<1, ≥1 to <6, ≥6 to <16, ≥16 to <45, ≥45 years). Overall, 413 paediatric liver transplantations from deceased donors were performed; 1- and 5-year graft survival rates were 75%, 80%, 78%, 81%, 74% and 75%, 64%, 70%, 67%, 46%, and 1- and 5-year patient survival rates were 88%, 91%, 90%, 89%, 78% and 88%, 84%, 84%, 83%, 63% for groups 1-5, respectively, without significant difference. Eight children received organs from donors younger than 1 year and 45 children received organs from donors between 1 and 6 years of age. Overall, vascular complications occurred in 13.2% of patients receiving organs from donors younger than 6 years. Analysis of our data revealed that the usage of liver grafts from donors younger than 6 years is a safe procedure. The outcome was comparable with grafts from older donors with excellent graft and patient survival, even for donors younger than 1 year.


Assuntos
Transplante de Fígado/métodos , Adolescente , Adulto , Síndrome de Alagille/cirurgia , Criança , Pré-Escolar , Colestase Intra-Hepática/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Resultado do Tratamento
20.
Transpl Int ; 24(8): 805-11, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21615550

RESUMO

In children with renal insufficiency and accompanying or underlying liver disease, combined liver and kidney transplantations (CLKT) are indicated. However, because of the rare indications, the number of paediatric CLKT is low. Our aim was to analyse CLKT in children with special regard to surgical aspects and outcome. All paediatric CLKT performed at our institution between 1998 and 2009 were retrospectively analysed. Between 1998 and 2009, 15 CLKT were performed in 14 paediatric patients (median age 8 years, range 1-16 years). The indications for CLKT were autosomal recessive polycystic kidney disease (n = 7), primary hyperoxaluria type 1 (n = 7) and retransplantation because of primary liver nonfunction (n = 1). In the postoperative course, six patients showed bleeding complications, thereof three patients needed operative revision for intra-abdominal bleeding. Eight of 15 patients (53%) needed dialysis. The 1- and 5-year patient survival was 100%; and 1- and 5-year graft survival was 80% for the liver and 93% for the kidney allograft. A number of different complications, especially secondary haemorrhage have to be anticipated after CLKT, requiring a timely and interdisciplinary treatment approach. With this management, our patients showed an excellent graft and patient survival.


Assuntos
Hiperoxalúria Primária/terapia , Transplante de Rim/métodos , Transplante de Fígado/métodos , Doenças Renais Policísticas/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Recém-Nascido , Masculino , Veia Porta/patologia , Complicações Pós-Operatórias , Diálise Renal , Resultado do Tratamento
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