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1.
Ann Surg ; 267(3): 419-425, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28885508

RESUMEN

: 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.


Asunto(s)
Benchmarking , Trasplante de Hígado/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/epidemiología , Femenino , Humanos , Masculino , Análisis de Supervivencia
2.
Clin Transplant ; 32(3): e13205, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29345754

RESUMEN

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.


Asunto(s)
Trasplante de Hígado/mortalidad , Complicaciones Posoperatorias/mortalidad , Donantes de Tejidos , Obtención de Tejidos y Órganos/normas , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Listas de Espera , Adulto Joven
3.
Pediatr Transplant ; 21(6)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28580726

RESUMEN

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.


Asunto(s)
Atresia Biliar/complicaciones , Colangitis Esclerosante/cirugía , Cirrosis Hepática/cirugía , Trasplante de Hígado/métodos , Enfermedad de la Orina de Jarabe de Arce/cirugía , Adolescente , Femenino , Humanos , Lactante , Cirrosis Hepática/etiología , Adulto Joven
4.
Transpl Infect Dis ; 18(6): 850-855, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27639176

RESUMEN

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.


Asunto(s)
Virus BK/efectos de los fármacos , Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/uso terapéutico , Enfermedades Renales/epidemiología , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/epidemiología , Infecciones Tumorales por Virus/epidemiología , Viremia/epidemiología , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Virus BK/aislamiento & purificación , Basiliximab , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/uso terapéutico , Everolimus/administración & dosificación , Everolimus/efectos adversos , Everolimus/uso terapéutico , Femenino , Alemania/epidemiología , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Incidencia , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Enfermedades Renales/virología , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Infecciones por Polyomavirus/virología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Infecciones Tumorales por Virus/virología , Viremia/virología
5.
Clin Transplant ; 29(11): 1021-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26333844

RESUMEN

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.


Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Incompatibilidad de Grupos Sanguíneos/inmunología , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Everolimus/uso terapéutico , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Pruebas de Función Renal , Donadores Vivos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Tacrolimus/uso terapéutico
6.
Ther Drug Monit ; 37(4): 539-45, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25525763

RESUMEN

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.


Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Glucuronatos/análisis , Cabello/química , Trasplante de Hígado/métodos , Detección de Abuso de Sustancias/métodos , Biomarcadores/análisis , Biomarcadores/sangre , Biomarcadores/orina , Etanol/sangre , Femenino , Glucuronatos/orina , Humanos , Masculino , Metanol/sangre , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Transferrina/análogos & derivados , Transferrina/metabolismo
7.
Liver Int ; 34(3): 469-76, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23829409

RESUMEN

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.


Asunto(s)
Abstinencia de Alcohol , Glucuronatos/química , Cabello/química , Cirrosis Hepática Alcohólica/diagnóstico , Trasplante de Hígado , Adulto , Consumo de Bebidas Alcohólicas , Biomarcadores , Etanol/sangre , Etanol/química , Femenino , Humanos , Masculino , Metanol/sangre , Metanol/química , Persona de Mediana Edad , Sensibilidad y Especificidad , Transferrina/análogos & derivados , Transferrina/química
8.
Pediatr Transplant ; 18(4): 377-84, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24802344

RESUMEN

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.


Asunto(s)
Supervivencia de Injerto , Trasplante de Hígado/mortalidad , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Trasplante de Hígado/métodos , Masculino , Evaluación del Resultado de la Atención al Paciente , Reoperación/métodos , Reoperación/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo
10.
Transpl Int ; 26(12): 1217-24, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24118382

RESUMEN

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.


Asunto(s)
Trasplante de Hígado/métodos , Hígado/anatomía & histología , Adolescente , Autopsia , Peso Corporal , Niño , Preescolar , Funcionamiento Retardado del Injerto , Supervivencia de Injerto , Humanos , Lactante , Hígado/crecimiento & desarrollo , Tamaño de los Órganos
11.
Transpl Int ; 26(6): 640-50, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23582048

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Trasplante de Hígado , Hígado/patología , Riñón Poliquístico Autosómico Recesivo/cirugía , Adolescente , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Hipertensión Portal/patología , Hipertensión Portal/cirugía , Lactante , Fallo Renal Crónico/patología , Fallo Renal Crónico/cirugía , Hígado/diagnóstico por imagen , Cirrosis Hepática/patología , Masculino , Riñón Poliquístico Autosómico Recesivo/genética , Riñón Poliquístico Autosómico Recesivo/patología , Receptores de Superficie Celular/genética , Estudios Retrospectivos , Ultrasonografía
12.
Pediatr Transplant ; 17(8): 757-64, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24164827

RESUMEN

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.


Asunto(s)
Biomarcadores/sangre , Trasplante de Hígado , Linfocitos T Reguladores/citología , Adolescente , Linfocitos T CD8-positivos/citología , Separación Celular , Niño , Preescolar , Estudios Transversales , Femenino , Citometría de Flujo , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Lactante , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Trasplante de Riñón , Masculino , Tacrolimus/uso terapéutico , Factor de Crecimiento Transformador beta/sangre
13.
Hepatology ; 54(5): 1640-9, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21809364

RESUMEN

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.


Asunto(s)
Consumo de Bebidas Alcohólicas/orina , Glucuronatos/orina , Hepatopatías Alcohólicas , Trasplante de Hígado , Tamizaje Masivo/métodos , Templanza , Adulto , Anciano , Femenino , Humanos , Hepatopatías Alcohólicas/diagnóstico , Hepatopatías Alcohólicas/cirugía , Hepatopatías Alcohólicas/orina , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Prevención Secundaria , Sensibilidad y Especificidad , Listas de Espera , Adulto Joven
14.
Transpl Int ; 25(11): 1158-64, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22882364

RESUMEN

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.


Asunto(s)
Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/efectos adversos , Adulto , Anciano , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Inhibidores de la Calcineurina , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Trasplante de Hígado , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/efectos adversos , Recurrencia , Estudios Retrospectivos , Sorafenib , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Resultado del Tratamiento
15.
Front Pharmacol ; 13: 1009612, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36267268

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-21280182

RESUMEN

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.


Asunto(s)
Implantes Absorbibles , Hepatocitos/trasplante , Ácido Láctico , Regeneración Hepática , Polímeros , Ingeniería de Tejidos/métodos , Andamios del Tejido , Biomarcadores/metabolismo , Reactores Biológicos , Northern Blotting , Separación Celular , Forma de la Célula , Supervivencia Celular , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Hepatocitos/metabolismo , Hepatocitos/ultraestructura , Humanos , Inmunohistoquímica , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Poliésteres , Albúmina Sérica/genética , Albúmina Sérica/metabolismo , Factores de Tiempo , Urea/metabolismo , alfa 1-Antitripsina/metabolismo
18.
Biotechnol Bioeng ; 108(1): 141-50, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20824672

RESUMEN

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.


Asunto(s)
Hepatocitos/fisiología , Hígado Artificial , Polímeros , Andamios del Tejido , Animales , Supervivencia Celular , Células Cultivadas , Nanofibras , Técnicas de Cultivo de Órganos , Farmacología/métodos , Ratas , Ingeniería de Tejidos/métodos , Toxicología/métodos
19.
Transpl Int ; 24(6): 610-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21401730

RESUMEN

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.


Asunto(s)
Trasplante de Hígado/métodos , Adolescente , Adulto , Síndrome de Alagille/cirugía , Niño , Preescolar , Colestasis Intrahepática/cirugía , Femenino , Supervivencia de Injerto , Humanos , Lactante , Fallo Hepático Agudo/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Donadores Vivos , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Resultado del Tratamiento
20.
Transpl Int ; 24(8): 805-11, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21615550

RESUMEN

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.


Asunto(s)
Hiperoxaluria Primaria/terapia , Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Enfermedades Renales Poliquísticas/terapia , Adolescente , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Masculino , Vena Porta/patología , Complicaciones Posoperatorias , Diálisis Renal , Resultado del Tratamiento
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