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1.
Transplant Proc ; 50(10): 3211-3215, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30577187

RESUMEN

BACKGROUND: An analysis of 2 kidney transplants from the same donor at the same center enables us to analyze the influence of risk factors on the outcome of the grafts in different recipients. METHODS: We retrospectively analyzed 88 kidneys from 44 donors that were implanted in 88 recipients at our institution between 2007-2016. We defined unsatisfactory outcome as glomerular filtration rate <30 mL/min/1.73 m2 allograft loss or recipient death within the first year after transplantation. Fifty-three kidneys were allocated and age-matched to donors above the age of 65 years (via Eurotransplant Senior Program or center offer). We compared kidney pairs with satisfactory outcome in both recipients (group A) to pairs with divergent outcome (group B) and unsatisfactory outcome in both recipients (group C). RESULTS: Thirty-four grafts (17 donors) had a satisfactory outcome for both recipients (group A), and 16 grafts (8 donors) had an unsatisfactory outcome for both recipients (group C). Donor age was significantly higher in group C vs group A (67.5 ± 6.7 vs 56.4 ± 16.0 years, P = .010). The 19 donors donating 1 kidney with satisfactory and the other with unsatisfactory outcome were 67.4 ± 10.7 years old (group B). A severe surgical complication occurred more often in recipients with an unsatisfactory outcome in comparison to patients with a satisfactory outcome. CONCLUSION: Donor age is an important risk factor for an unsatisfactory outcome, either in one or both kidneys of the same donor.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Factores de Edad , Anciano , Aloinjertos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos/provisión & distribución , Trasplante Homólogo , Resultado del Tratamiento
2.
United European Gastroenterol J ; 6(1): 104-111, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29435320

RESUMEN

BACKGROUND: Since introduction of the MELD score in the liver allograft allocation system, renal insufficiency has emerged as an increasing problem. Here we evaluated the course of kidney function in patients with advanced renal insufficiency prior to liver transplantation (LT). METHODS: A total of 254 patients undergoing LT at the University Medical Centre Hamburg-Eppendorf (2011-2015) were screened for renal impairment (GFR < 30 ml/min) prior to LT in this observational study. RESULTS: Eighty (32%) patients (median 60 years; M/F: 48/32) had significant renal impairment prior to LT. Median follow-up post-LT was 619 days. Patient survival at 90 days, one year and two years was 76%, 66% and 64%, respectively. Need for dialysis postoperatively but not preoperatively was associated with increased mortality (p < 0.05). Renal function improved in 75% of survivors, but 78% of patients had chronic kidney disease ≥ stage 3 at end of follow-up. Of eight (16%) survivors remaining on long-term dialysis, so far only four patients have received a kidney transplant. CONCLUSION: Postoperative dialysis affected long-term mortality. In 75% of survivors renal function improved, but still the majority of patients had an impaired renal function (CKD stage 3-5) at end of follow-up. Future studies should elucidate the impact of kidney dysfunction and dialysis on recipients' long-term survival.

3.
HLA ; 91(1): 52-55, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29111570

RESUMEN

The killer cell lectin-like receptor B1 (KLRB1) gene encodes for CD161 expressed by different subsets of leukocytes involved in the development of acute liver transplant rejection. The single nucleotide polymorphism (SNP) 503T>C (rs1135816) in the KLRB1 gene represents a missense mutation modifying functional properties of CD161. The aim of our study is to determine whether the SNP 503T>C is associated with acute liver transplant rejection. We genotyped the SNP for 163 liver recipients without acute rejection, 125 recipients with a single acute rejection, and 53 recipients with multiple acute rejections. The genotype frequencies within the groups did not show any significant difference. Our data suggest that the SNP 503T>C has no impact on the susceptibility of acute liver transplant rejection.


Asunto(s)
Predisposición Genética a la Enfermedad , Rechazo de Injerto/genética , Trasplante de Hígado , Subfamilia B de Receptores Similares a Lectina de Células NK/genética , Polimorfismo de Nucleótido Simple , Enfermedad Aguda , Adulto , Anciano , Femenino , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología
4.
Transpl Infect Dis ; 18(3): 326-32, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26988272

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting. METHODS: All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit. RESULTS: SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed. CONCLUSION: Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.


Asunto(s)
Antivirales/farmacología , Bencimidazoles/farmacología , Fluorenos/farmacología , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Ribavirina/farmacología , Sofosbuvir/farmacología , Anciano , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Europa (Continente) , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
5.
Transpl Infect Dis ; 18(1): 79-88, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26707694

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) is a risk factor for patient and graft survival after kidney transplantation. METHODS: We retrospectively analyzed risk factors for CMV infection in 348 patients who received a kidney transplant donated after brain death (n = 232) or by living donation (n = 116) between 2008 and 2013. Of the 348 patients analyzed, 91 received a mammalian target of rapamycin inhibitor (mTORi)-based immunosuppressive regimen. A total of 266 patients were treated with standard immunosuppression (Group 1) consisting of basiliximab induction, calcineurin inhibitor (CNI), and either mycophenolic acid (MPA, n = 219) or everolimus (EVE) (n = 47). We also included 82 patients who received more intense immunosuppression (Group 2) with lymphocyte depletion, CNI, plus either MPA (n = 38) or EVE (n = 44). Only patients in the high-risk constellation received CMV prophylaxis in Group 1, while all patients in Group 2 received prophylaxis for 6 month. RESULTS: The overall rate of CMV infections was low with 10.1% in all patients. Despite the different prophylaxis strategies applied, no difference was seen in CMV infections between Group 1 (10.9%) and Group 2 (13.6%). A multivariate analysis revealed that patients on EVE had fewer CMV complications compared with patients on MPA (P = 0.013, odds ratio [OR] 4.8, confidence interval [CI] 1.4-16.5). Donor and recipient age >65 years was an independent risk factor (P = 0.002, OR 3.2, CI 1.5-6.7) for CMV infections. Patients with CMV infections had significantly worse graft function after 2 years (P = 0.001). CONCLUSION: CMV is a significant risk factor for long-term graft outcome. Patients treated with EVE developed fewer CMV complications compared to patients on MPA. The use of mTORi is useful in patients at high risk of developing CMV infections.


Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Citomegalovirus/aislamiento & purificación , Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Anciano , Estudios de Cohortes , Infecciones por Citomegalovirus/virología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Terapia de Inmunosupresión , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Estudios Retrospectivos
6.
Oncogene ; 35(29): 3872-9, 2016 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-26549021

RESUMEN

Hepatocellular carcinoma (HCC) is a frequent form of cancer with a poor prognosis and with limited possibilities of medical intervention. It has been shown that over 100 putative driver genes are associated with multiple recurrently altered pathways in HCC, suggesting that multiple pathways will need to be inhibited for any therapeutic method. mRNA processing is regulated by a complex RNA-protein network that is essential for the maintenance of homeostasis. THOC5, a member of mRNA export complex, has a role in less than 1% of mRNA processing, and is required for cell growth and differentiation, but not for cell survival in normal fibroblasts, hepatocytes and macrophages. In this report, we show that 50% depletion of THOC5 in human HCC cell lines Huh7 and HepG2 induced apoptosis. Transcriptome analysis using THOC5-depleted cells revealed that 396 genes, such as transmembrane BAX inhibitor motif containing 4 (TMBIM4), transmembrane emp24-like trafficking protein 10 (Tmed10) and D-tyrosyl-tRNA deacylase 2 (Dtd2) genes were downregulated in both cell lines. The depletion of one of these THOC5 target genes in Huh7 or HepG2 did not significantly induce cell death, suggesting that these may be fine tuners for HCC cell survival. However, the depletion of a combination of these genes synergistically increased the number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive HCC. It must be noted that the depletion of these genes did not induce cell death in the hepatocyte cell line, THLE-2 cells. THOC5 expression was enhanced in 78% of cytological differentiation grading G2 and G3 tumor in primary HCC. Furthermore, the expression of a putative glycoprotein, Tmed10, is correlated to THOC5 expression level in primary HCCs, suggesting that this protein may be a novel biomarker for HCC. These data imply that the suppression of the multiple THOC5 target genes may represent a novel strategy for HCC therapy.


Asunto(s)
Apoptosis/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/genética , Interferencia de ARN , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular , Línea Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Immunoblotting , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Nucleares/metabolismo , Transporte de ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
7.
Transpl Infect Dis ; 18(1): 141-5, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26485543

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. METHODS: All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). RESULTS: HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. CONCLUSIONS: DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Sofosbuvir/uso terapéutico , Adulto , Anciano , Estudios de Cohortes , Femenino , Hepacivirus/genética , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Ribavirina/uso terapéutico , Proteínas del Núcleo Viral/sangre , Carga Viral
10.
Transpl Infect Dis ; 17(4): 617-22, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26094550

RESUMEN

The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case of chronic hepatitis E was observed in patients with normal liver enzymes, indicating that general screening of all OLT recipients is not necessary. However, if chronic hepatitis E develops, it can be treated efficiently with ribavirin.


Asunto(s)
Hepatitis E/diagnóstico , Hepatitis Crónica/diagnóstico , Trasplante de Hígado , Complicaciones Posoperatorias/diagnóstico , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Hepatitis E/tratamiento farmacológico , Hepatitis E/etiología , Hepatitis Crónica/tratamiento farmacológico , Hepatitis Crónica/etiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Adulto Joven
11.
Tissue Antigens ; 84(4): 370-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25112903

RESUMEN

The nuclear factor of kappa light polypeptide gene enhancer B-cells inhibitor-alpha (NFKBIA) gene encodes a member of the nuclear factor-kappa-B inhibitor family. Polymorphisms in this gene might be associated with a susceptibility to acute rejection episodes following liver transplantation, as they may cause an increased activation level of the proinflammatory transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB). The aim of this study was to evaluate whether the NFKBIA polymorphisms -297 C/T (rs2233409), -826 C/T (rs2233406) and 126 G/A (rs696) affect the incidence of acute liver graft rejection. A total of 199 liver transplant recipients was analyzed, 100 without (NAR) and 99 with early acute rejection (AR). Thirty-two individuals with multiple acute rejections (MAR) were analyzed as a subgroup of AR. Polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and allele-specific hybridization with fluorescence resonance energy transfer (FRET) were used for genotyping. We identified the genotype NFKBIA 126 AA (P = 0.002) as well as the haplotype NFKBIA-126A-297T-826T (P = 0.002) as a potential risk factor for the occurrence of recurrent acute rejections. Furthermore, we assessed an association between the 126 A allele and susceptibility to recurrent acute rejections (P = 0.027). Our data suggest that the NFKBIA 126 G/A polymorphism might be potentially helpful to identify liver transplant recipients with an increased susceptibility to develop recurrent acute rejections.


Asunto(s)
Alelos , Predisposición Genética a la Enfermedad , Rechazo de Injerto/genética , Proteínas I-kappa B/genética , Trasplante de Hígado , Polimorfismo Genético , Enfermedad Aguda , Adulto , Femenino , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Inhibidor NF-kappaB alfa , Reacción en Cadena de la Polimerasa
12.
Am J Transplant ; 14(8): 1817-27, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25041339

RESUMEN

This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N = 260) to one of the following immunosuppressive regimens: (i) basiliximab + belatacept high dose [HD] + mycophenolate mofetil (MMF), (ii) belatacept HD + MMF, (iii) belatacept low dose [LD] + MMF, (iv) tacrolimus + MMF, or (v) tacrolimus alone. All received corticosteroids. Demographic characteristics were similar among groups. The proportion of patients who met the primary end point (composite of acute rejection, graft loss, death by month 6) was higher in the belatacept groups (42­48%) versus tacrolimus groups (15­38%), with the highest number of deaths and grafts losses in the belatacept LD group. By month 12, the proportion surviving with a functioning graft was higher with tacrolimus + MMF (93%) and lower with belatacept LD (67%) versus other groups (90%: basiliximab + belatacept HD; 83%: belatacept HD; 88%: tacrolimus). Mean calculated GFR was 15­34 mL/min higher in belatacept-treated patients at 1 year. Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept-treated patients. Follow-up beyond month 12 revealed an increase in death and graft loss in another belatacept group (belatacept HD), after which the study was terminated.


Asunto(s)
Inmunoconjugados/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Abatacept , Adulto , Anciano , Esquema de Medicación , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Hepatitis C/mortalidad , Hepatitis C/cirugía , Humanos , Inmunoconjugados/administración & dosificación , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Leucoencefalopatías/complicaciones , Fallo Hepático/mortalidad , Fallo Hepático/cirugía , Trastornos Linfoproliferativos/complicaciones , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Recurrencia , Tacrolimus/administración & dosificación , Resultado del Tratamiento
13.
Am J Transplant ; 13(11): 2956-65, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24102763

RESUMEN

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.


Asunto(s)
Trastornos del Conocimiento/etiología , Trasplante de Hígado/efectos adversos , Síndrome Metabólico/genética , Adolescente , Niño , Desarrollo Infantil , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Masculino , Pronóstico , Factores de Riesgo
14.
Clin Transplant ; 27(6): E625-35, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24033455

RESUMEN

Data were pooled from three prospective, multicenter trials in which 1996 de novo kidney transplant recipients were randomized to everolimus 1.5 or 3.0 mg or mycophenolic acid (MPA), with cyclosporine and steroids. Wound healing complications reported as adverse events were retrospectively reviewed in a blinded manner. The incidence of wound healing adverse events was 17.6% (351 of 1996) by day 90 and was similar for everolimus 1.5 mg (16.6% [110 of 661]) vs. MPA (14.3% [95 of 665]) (p = 0.255), but higher with everolimus 3.0 mg (21.8% [146 of 670]) (p < 0.001 vs. MPA). Similar results were observed for wound healing complications reported as serious adverse events. The 12-month incidence of lymphocele was 11.2% with everolimus 1.5 mg and 8.9% with MPA (p = 0.171), but lymphocele reported as a serious adverse event were more frequent with everolimus 1.5 mg (6.5% vs. 3.5%; p = 0.012). The hazard ratio (HR) for any wound healing complication vs. MPA was not significantly higher for everolimus <3 ng/mL (HR 1.33; 95% CI 0.94-1.88; p = 0.104), but increased to 1.46 (95% CI 1.12-1.90; p = 0.005) for 3-8 ng/mL and 1.69 (95% CI 1.20-2.38; p = 0.002) for >8 ng/mL. These results suggest that de novo kidney transplant patients receiving an initial everolimus dose of 1.5 mg do not appear to have a pronounced increased risk of wound healing complications vs. patients receiving MPA.


Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Sirolimus/análogos & derivados , Cicatrización de Heridas/efectos de los fármacos , Adulto , Ciclosporina/uso terapéutico , Everolimus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto/efectos de los fármacos , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Sirolimus/uso terapéutico
15.
Int J Immunogenet ; 39(5): 437-41, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22524693

RESUMEN

This study was carried out to evaluate the association between 77C>G transversion (rs17612648) in exon A of the PTPRC gene and liver transplant rejection. No significant differences in genotype and allele frequencies of the 77C>G transversion were detected between recipients without rejection (n = 106) and recipients with rejection (n = 104). In conclusion, there was no evidence for the contribution of the 77C>G transversion in susceptibility to liver transplant rejection in a Caucasian population.


Asunto(s)
Exones , Predisposición Genética a la Enfermedad , Rechazo de Injerto/genética , Antígenos Comunes de Leucocito/genética , Trasplante de Hígado/patología , Adulto , Anciano , Citosina/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética/métodos , Genotipo , Rechazo de Injerto/metabolismo , Supervivencia de Injerto , Guanina/metabolismo , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Población Blanca/genética
16.
Am J Transplant ; 11(7): 1444-55, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21564523

RESUMEN

Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1:2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (± standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 ± 22.3 vs. 49.5 ± 17.7 mL/min/1.73 m(2) , p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.


Asunto(s)
Trasplante de Riñón/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Pirroles/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Inhibidores de la Calcineurina , Femenino , Humanos , Masculino , Ácido Micofenólico/uso terapéutico , Tacrolimus/uso terapéutico
17.
Z Gastroenterol ; 49(1): 30-8, 2011 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-21225535

RESUMEN

Liver transplantation represents a successful and well-established therapeutic concept for patients with advanced liver diseases. Organ donor shortage continues to pose a significant problem. To ensure fair and transparent allocation of too few post-mortem grafts, the model of end-stage liver disease (MELD)-based allocation was implemented in December 2006. This has decreased waiting list mortality from 20 to 10 % but at the same time has reduced post OLT survival (1-year survival from almost 90% to below 80%), which is largely due to patients with a labMELD score > 30. Following MELD introduction the regular allocation threshold has increased from a matchMELD of initially 25 to meanwhile 34. At the same time the quality of donor organs has seen a continuous deterioration over the last 10 - 15 years: 63% of organs are "suboptimal" with a donor risk index of > 1.5. Moreover, the numbers of living-related liver transplantations have decreased. In Germany incentives for transplant centres are inappropriate: patients with decompensated cirrhosis, high MELD scores and high post-transplant mortality as well as marginal liver grafts are accepted for transplantation without the necessary consideration of outcomes, and against a background of the still absent publication and transparency of outcome results. The outlined development calls for measures for improvement: (i) the increase of donor grafts (e. g., living donation, opt-out solutions, non-heart beating donors), (ii) the elimination of inappropriate incentives for transplant centres, (iii) changes of allocation guidelines, that take the current situation and suboptimal donor grafts into account, and (iv) the systematic and complete collection of transplant-related data in order to allow for the development of improved prognostic scores.


Asunto(s)
Asignación de Recursos para la Atención de Salud/estadística & datos numéricos , Asignación de Recursos para la Atención de Salud/tendencias , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Selección de Paciente , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Alemania/epidemiología , Humanos , Motivación
19.
Transplant Proc ; 39(10): 2937-50, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18089298

RESUMEN

While advances in immunosuppressive therapy have allowed dramatic improvements in the control of acute allograft rejection, there is still a need to improve long-term graft and patient survival rates following renal and heart transplantation. Among the recognized threats to long-term organ survival are chronic allograft dysfunction in the form of chronic allograft nephropathy and cardiac allograft vasculopathy, with long-term patient morbidity and mortality further compromised by higher than normal rates of posttransplant cardiovascular disease, infection, and malignancy. A growing body of evidence finds that the selection and dosing of immunosuppressive therapies can have great influence on long-term transplantation outcomes. Early evidence suggests that the proliferation signal inhibitors (PSIs), everolimus and sirolimus, might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the posttransplant patient. This review summarizes the emerging evidence for employing PSI-based immunosuppression to seek a balance between the goals of maximizing graft and patient survival, while minimizing the risks of adverse events and long-term complications. Based on the proceedings of an international gathering of nephrologists, cardiologists and surgeons at the inaugural PSI Forum meeting "Proliferation signal inhibitors in transplantation: questions at the cutting edge," this paper aims to provide both an evidence base and practical guidance for transplant physicians seeking to optimize their use of PSI treatment and highlights avenues of ongoing research into the clinical potential of this class of immunosuppressive therapy.


Asunto(s)
División Celular/efectos de los fármacos , Inmunosupresores/uso terapéutico , Sirolimus/análogos & derivados , Inmunología del Trasplante , Everolimus , Rechazo de Injerto/prevención & control , Humanos , Transducción de Señal/efectos de los fármacos , Sirolimus/uso terapéutico , Trasplante Homólogo/inmunología
20.
Ultraschall Med ; 28(6): 587-92, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18074312

RESUMEN

AIM: Evaluation of the influence of arterial anastomoses on hepatic hemodynamics and overall survival in liver graft recipients using color Doppler ultrasound. METHOD: 224 patients recruited retrospectively were divided into five groups according to arterial anastomoses: (1) common hepatic (CHA)/gastro duodenal, (2) CHA/CHA, (3) aorta/celiac trunc, (4) aorta/aorta, (5) more than one anastomosis. We compared maximum portal [(P)Vmax], systolic [(A)Vmax] and end diastolic [(A)Vmin] arterial velocities, resistance indexes(RI), spleen and liver size between the groups. We analyzed further in a multivariate analysis the influence of time elapsed since orthotopic liver transplantation, age of recipient and donor on significant parameters as well as the overall survival of the patients between the groups. RESULTS: Significant differences were found for: (A) Vmax between groups 2/4 (p<0.007) and 2/5 (p<0.010), (A) Vmin between groups 1/3 (p<0.029) and 2/3 (p<0.015) and RI between the groups 1/3 (p<0.018) and 3/4 (p<0.006). (A)Vmax and RI were only dependent on the type of arterial anastomosis (p<0.008 and p<0.014). The overall survival of the patients between the groups was significantly different (p<0.047). CONCLUSION: In this study we report the natural course of the mean values of portal and arterial velocities in different arterial reconstructions for the first time. (A) Vmax of the hepatic artery is identified as the most promising candidate prognostic parameter for the assessment of hemodynamic alterations after liver transplantation originating in the type of arterial anastomosis performed. The group of patients with more than one anastomosis had the lowest arterial (A) Vmax and simultaneously the lowest overall survival.


Asunto(s)
Anastomosis Quirúrgica/métodos , Hemodinámica , Arteria Hepática/cirugía , Trasplante de Hígado/métodos , Trasplante de Hígado/fisiología , Adulto , Aorta Abdominal/fisiopatología , Aorta Abdominal/cirugía , Femenino , Estudios de Seguimiento , Humanos , Hepatopatías/clasificación , Hepatopatías/cirugía , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Vena Porta/fisiopatología , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo
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