RESUMO
In recent years, significant progress has been made in the field of liver machine perfusion. Many large transplant centers have implemented machine perfusion strategies in their clinical routine. Normothermic machine perfusion (NMP) is primarily used to determine the quality of extended criteria donor (ECD) organs and for logistical reasons. The vast majority of studies, which assessed the viability of perfused grafts, focused on hepatocellular injury. However, biliary complications are still a leading cause of post-transplant morbidity and the need for re-transplantation. To evaluate the extent of biliary injury during NMP, reliable criteria that consider cholangiocellular damage are needed. In this review, different approaches to assess damage to the biliary tree and the current literature on the possible effects of NMP on the biliary system and biliary injury have been summarized. Additionally, it provides an overview of novel biomarkers and therapeutic strategies that are currently being investigated. Although expectations of NMP to adequately assess biliary injury are high, scant literature is available. There are several biomarkers that can be measured in bile that have been associated with outcomes after transplantation, mainly including pH and electrolytes. However, proper validation of those and other novel markers and investigation of the pathophysiological effect of NMP on the biliary tree is still warranted.
Assuntos
Sistema Biliar , Transplante de Fígado , Biomarcadores , Humanos , Fígado , Transplante de Fígado/efeitos adversos , Preservação de Órgãos , PerfusãoRESUMO
BACKGROUND AND AIMS: The Model for End-Stage Liver Disease (MELD) is used for clinical decision-making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD-Na). However, MELD-Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF-Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF-Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. APPROACH AND RESULTS: Hence, WF-Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting-list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF-Ag (P < 0.001). MELD-Na and vWF-Ag were comparable and independent in their predictive potential for 3-month mortality on the waiting list (area under the curve [AUC], vWF-Ag = 0.739; MELD-Na = 0.764). Importantly, a vWF-Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD-Na of 20 points (vWF-Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD-Na, OR = 7.594, 95% CI, 2.578, 22.372; P < 0.001, respectively). Ultimately, inclusion of vWF-Ag into the MELD-Na equation significantly improved prediction of 3-month waiting-list mortality (AUC, MELD-Na-vWF = 0.804). CONCLUSIONS: A single measurement of vWF-Ag at listing for OLT predicts early mortality. Combining vWF-Ag levels with MELD-Na improves risk stratification and may help to prioritize organ allocation to decrease waiting-list mortality.
Assuntos
Doença Hepática Terminal/sangue , Doença Hepática Terminal/mortalidade , Transplante de Fígado , Listas de Espera/mortalidade , Fator de von Willebrand/análise , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Valor Preditivo dos Testes , Medição de Risco/métodos , Índice de Gravidade de Doença , Taxa de Sobrevida , Adulto JovemRESUMO
The quantification of donor-derived cell-free DNA (ddcfDNA) in recipient's plasma is a novel, but technically challenging noninvasive method to assist the diagnosis of acute rejection (AR). A quantitative real-time PCR (qPCR) approach targeting insertion/deletion polymorphisms (INDEL) was adapted to measure ddcfNA in plasma samples from 29 kidney transplant recipients obtained at time of clinically indicated biopsies (eight patients with a histologically verified AR, nine with borderline rejection and 12 without evidence of rejection). Measured ddcfDNA levels of smaller INDEL amplicon targets differed significantly (P = 0.016, Kruskal-Wallis H test) between recipients with biopsy-proven AR (median 5.24%; range 1.00-9.03), patients without (1.50%; 0.41-6.50) and patients with borderline AR (1.91%; 0.58-5.38). Similarly, pairwise testing by Mann-Whitney U-tests revealed significant differences between recipients with AR and without AR (P = 0.012) as well as patients with AR and borderline histology (P = 0.015). Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve for discriminating AR and non-AR biopsies of 0.84 (95% CI: 0.66-1.00). The determined cutoff value of 2.7% ddcfDNA showed a sensitivity of 0.88 (95% CI: 0.63-1.00) and specificity of 0.81 (95% CI: 0.64-0.98). INDEL qPCR represents a novel method to quantify ddcfDNA on standard qPCR instruments within 6-8 h with high sensitivity and specificity to detect AR.
Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Biomarcadores , Rejeição de Enxerto/diagnóstico , Humanos , Transplante de Rim/efeitos adversos , Projetos Piloto , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.
Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/provisão & distribuição , Adolescente , Adulto , Aloenxertos , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: We aimed to compare routine preoperative color-coded duplex ultrasound (DUS) to clinical examination (CE) alone in surgery for arteriovenous fistula (AVF) with special emphasis on long-term outcomes and cost effectiveness. METHODS: All patients undergoing an AVF formation or revision between January 1, 2011, and December 31, 2016, at our tertiary referral center were subject to analysis. Routine DUS was performed in 114 patients and CE alone in 217 patients. Primary and secondary patency, the need for revision or reintervention to obtain patency, and individual as well as overall costs were analyzed. RESULTS: Primary patency rate was higher in AVF after DUS compared with CE alone at 62% vs 26% (P < .05), respectively. Patients receiving DUS had significantly lower rates of revision and revisions per patient when compared with CE (25.4% vs 59.4% [P < .0001]; 0.36 ± 0.71 vs 1.06 ± 1.55 [P < .0001], respectively). Costs per patient were significantly lower in the DUS group compared with CE at 4074 vs 6078 (P < .0001). CONCLUSIONS: We were able to show that patients receiving preoperative DUS showed higher patency rates and needed fewer revisions. Standard preoperative ultrasound examination is an easy tool to improve outcomes and cost effectiveness in AVF surgery.
Assuntos
Derivação Arteriovenosa Cirúrgica/economia , Custos de Cuidados de Saúde , Cuidados Pré-Operatórios/economia , Diálise Renal/economia , Ultrassonografia Doppler em Cores/economia , Grau de Desobstrução Vascular , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Redução de Custos , Análise Custo-Benefício , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/economia , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/efeitos adversos , Reoperação/economia , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler em Cores/efeitos adversosRESUMO
We assessed whether standardized application of an absorbable polysaccharide hemostatic powder (HaemoCer™) has an effect on lymphocele rate after kidney transplantation. For this nonrandomized prospective trial, we first aimed to know our center-specific lymphocele rate diagnosed by ultrasound imaging. We retrospectively assessed all patient records of the elapsed year resulting in a center-specific rate of 20%, this was consistent with literature. The power analysis showed that 108 patients were required to detect a 50% reduction in lymphocele rate. During the prospective study period, 155 patients undergoing kidney transplantation were recruited to receive HaemoCer™ intraoperatively. In two patients, the product accidentally was not used. Six patients were excluded from analysis because of failure to complete follow-up (one early death and five early graft failures). Of the remaining 147 patients, 15 developed lymphoceles, which represents a rate of 10.2%; (95% CI: 6.3-16.2%). Compared to the expected occurrence, this was significantly lower (P = 0.003). Lymphoceles appeared to be associated with preoperative donor-specific antibody, retransplantation and immunoadsorption in HLA or ABO incompatible donors. At our institution, the frequency of lymphoceles after kidney transplantation appeared to be significantly reduced when HaemoCer™ was applied routinely. The magnitude of the effect warrants randomized evaluation.
Assuntos
Hemostáticos/uso terapêutico , Transplante de Rim/métodos , Linfocele/prevenção & controle , Polissacarídeos/uso terapêutico , Adsorção , Adulto , Idoso , Coagulação Sanguínea , Feminino , Hemostasia , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peritônio/patologia , Complicações Pós-Operatórias/prevenção & controle , Pós , Estudos Prospectivos , Reoperação , Estudos RetrospectivosRESUMO
BACKGROUND: The product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT. METHODS: In this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI. RESULTS: Forty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32-0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41-0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46-0.8], P = 0.18). CONCLUSION: Based on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.
Assuntos
Injúria Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Falência Renal Crônica/cirurgia , Transplante de Fígado , Complicações Pós-Operatórias/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Elevated concentrations of D-dopachrome tautomerase (D-DT) were associated with adverse outcome in various clinical settings. However, no study assessed D-DT concentrations in patients requiring orthotopic liver transplantation (OLT). The aim of this observational study was to measure serum D-DT concentrations in patients undergoing OLT and associate D-DT with survival and acute kidney injury (AKI). METHODS: Forty-seven adults with end-stage liver disease undergoing OLT were included. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of D-DT for outcome and AKI after OLT. Survival was analyzed by Kaplan-Meier curves. RESULTS: Serum D-DT concentrations were greater in non-survivors than in survivors prior to OLT (86 [50-117] vs. 53 [31-71] ng/ml, P = 0.008), and on day 1 (357 [238-724] vs. 189 [135-309] ng/ml, P = 0.001) and day 2 (210 [142-471] vs. 159 [120-204] ng/ml, P = 0.004) following OLT. Serum D-DT concentrations predicted lethal outcome when measured preoperatively (AUC = 0.75, P = 0.017) and on postoperative day 1 (AUC = 0.75, P = 0.015). One-year survival of patients with preoperative D-DT concentrations >85 ng/ml was 50%, whereas that of patients with preoperative D-DT concentrations <85 ng/ml was 83% (Chi2 = 5.83, P = 0.016). In contrast, D-DT was not associated with AKI after OLT. CONCLUSION: In patients undergoing OLT, serum D-DT might predict outcome after OLT.
Assuntos
Injúria Renal Aguda/enzimologia , Oxirredutases Intramoleculares/sangue , Transplante de Fígado , Complicações Pós-Operatórias/enzimologia , Biomarcadores/sangue , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Análise de SobrevidaRESUMO
Orthotopic liver transplantation (OLT) represents a curative treatment option for end-stage liver disease (ESLD). Although epidemiology of ESLD has recently changed due to the rising prevalence of nonalcoholic fatty liver disease and the decreased burden of hepatitis C virus infections due to highly effective antiviral regimens, the management of portal hypertension (PHT) remains a clinical challenge in the pre- and post-OLT setting. The measurement of the hepatic venous pressure gradient represents the most reliable but invasive tool for assessment of the severity of PHT. Although novel liver ultrasound and magnetic resonance-based elastography methods have been developed, their value to screen for liver fibrosis and PHT in transplanted patients remains to be established. Nonselective beta-blockers represent the cornerstone of medical treatment of PHT, but more studies on their effects on clinical endpoints after OLT are needed. Statins are widely used to treat hyperlipidemia, which is a common condition after OLT. Although a growing body of evidence suggests that statins decrease portal pressure and PHT-related complications in ESLD, studies on potential benefits of statins after OLT are lacking. Finally, transjugular intrahepatic portosystemic shunts (TIPS) are effective in decreasing PHT and seem to decrease mortality on the OLT waiting list. Moreover, TIPS does not have an impact on liver function nor complicate the transplant surgical procedures. TIPS may also be used after OLT, but the evidence is limited. In conclusion, whereas the management of PHT in patients with ESLD is based on strong evidence, further data on the value of noninvasive monitoring tools as well as on medical and invasive treatment options in the post-OLT setting are needed to improve management strategies in patients with recurrent PHT after liver transplantation. Liver Transplantation 24 112-121 2018 AASLD.
Assuntos
Doença Hepática Terminal/cirurgia , Hipertensão Portal/terapia , Transplante de Fígado/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Constrição Patológica/prevenção & controle , Doença Hepática Terminal/etiologia , Doença Hepática Terminal/mortalidade , Veias Hepáticas/cirurgia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão Portal/etiologia , Hipertensão Portal/mortalidade , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Fígado/patologia , Fígado/cirurgia , Transplante de Fígado/métodos , Pressão na Veia Porta/efeitos dos fármacos , Veia Porta/efeitos dos fármacos , Veia Porta/fisiopatologia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Cuidados Pós-Operatórios/métodos , Guias de Prática Clínica como Assunto , Cuidados Pré-Operatórios/métodos , Índice de Gravidade de Doença , Transplantes/patologia , Transplantes/cirurgiaRESUMO
Experimental studies suggest that macrophage migration inhibitory factor (MIF) mediates ischemia/reperfusion injury during liver transplantation. This study assessed whether human liver grafts release MIF during preservation, and whether the release of MIF is proportional to the extent of hepatocellular injury. Additionally, the association between MIF and early allograft dysfunction (EAD) after liver transplantation was evaluated. Concentrations of MIF, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured in effluents of 38 liver grafts, and in serum of recipients. Concentrations of MIF in the effluent were greater than those in the recipients' serum before and after reperfusion (58 [interquartile range, IQR:23-79] µg/mL vs 0.06 [IQR:0.03-0.07] µg/mL and 1.3 [IQR:0.7-1.8] µg/mL, respectively; both P<.001). Effluent MIF concentrations correlated with effluent concentrations of the cell injury markers ALT (R=.51, P<.01), AST (R=.51, P<.01), CK (R=.45, P=.01), and LDH (R=.56, P<.01). Patients who developed EAD had greater MIF concentrations in effluent and serum 10 minutes after reperfusion than patients without EAD (Effluent: 80 [IQR:63-118] µg/mL vs 36 [IQR:20-70] µg/mL, P=.02; Serum: 1.7 [IQR:1.2-2.5] µg/mL vs 1.1 [IQR:0.6-1.7] µg/mL, P<.001). CONCLUSION: Human liver grafts release MIF in proportion to hepatocellular injury. Greater MIF concentrations in effluent and recipient's serum are associated with EAD after liver transplantation.
Assuntos
Biomarcadores/metabolismo , Rejeição de Enxerto/metabolismo , Oxirredutases Intramoleculares/metabolismo , Transplante de Fígado/efeitos adversos , Fígado/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Complicações Pós-Operatórias , Doadores de Tecidos , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Fígado/lesões , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.
Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/mortalidade , Índice de Gravidade de Doença , Adulto , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Listas de EsperaRESUMO
Belatacept was recently evaluated in liver transplantation (LT) in a phase II multicenter trial, which was terminated prematurely. Patients were more than two yr post-LT at the time. As high rates of spontaneous tolerance after LT have been reported and as belatacept has marked immunomodulatory effects, we decided to maintain the belatacept patients enrolled at our center (n = 4) on MMF monotherapy. All belatacept patients on MMF monotherapy developed graft dysfunction consistent with acute rejection after a mean period of 10.3 (7-14) wk. Patients were therefore switched to triple therapy with CNI, MMF, and corticosteroids. Graft dysfunction resolved within 1-3 wk after switch. At the time of belatacept discontinuation, mean eGFR was 105.1 mL/min/1.73 m² (92.1-118.9) in belatacept patients compared to 58 mL/min/1.73 m² (36.1-98.2) in controls (p = 0.022). One yr after the switch to CNI therapy, eGFR had declined by 27.4 mL (19.2-39.3; p = 0.008). Thus, LT patients treated with belatacept show superior kidney function that declines upon institution of CNIs. MMF monotherapy following withdrawal of belatacept is associated with a high incidence of graft dysfunction. Belatacept has no obvious immunomodulatory effects in LT recipients that would be sufficient to allow drug withdrawal with a high rate of success.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunoconjugados/farmacologia , Imunossupressores/farmacologia , Transplante de Fígado , Ácido Micofenólico/análogos & derivados , Tolerância ao Transplante/efeitos dos fármacos , Abatacepte , Corticosteroides/uso terapêutico , Adulto , Inibidores de Calcineurina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Término Precoce de Ensaios Clínicos , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Humanos , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoRESUMO
While belatacept has shown favorable short- and midterm results in kidney transplant recipients, only projections exist regarding its potential impact on long-term outcome. Therefore, we performed a retrospective case-match analysis of the 14 belatacept patients originally enrolled in the phase II multicenter trial at our center. Fifty six cyclosporine (CyA)-treated patients were matched according to age at transplantation, first/retransplant, and donor type. Ten years after kidney transplantation, kidney function remained superior in belatacept-treated patients compared with the CyA control group. Moreover, none of the belatacept-treated patients had donor-specific antibodies ≥10 years post-transplantation compared with 38.5% of tested CyA-treated subject (0/10 vs. 5/13; P = 0.045). Notably, however, patient and graft survival was virtually identical in both groups (71.4% vs. 71.3%; P = 0.976). In the present single-center study population, patients treated with belatacept demonstrated a patient and graft survival at 10 years post-transplant which was comparable to that of similarly selected CNI-treated patients. Larger studies with sufficient statistical power are necessary to definitively determine long-term graft survival with belatacept.
Assuntos
Abatacepte/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Idoso , Ciclosporina/uso terapêutico , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Testes de Função Renal , Transplante de Rim/mortalidade , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.
Assuntos
Falência Hepática/cirurgia , Transplante de Fígado/métodos , Europa (Continente) , Humanos , Inflamação , Internet , Estudos Multicêntricos como Assunto , Preservação de Órgãos/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reperfusão/métodos , Soluções , Inquéritos e QuestionáriosRESUMO
PURPOSE: Traditionally, abdominal drainage (AD) is routinely inserted in patients after liver transplantation (LT) to drain ascites and to detect postoperative hemorrhage and bile leakage. However, the benefit of this surgical practice remains a matter of debate regarding potential drainage-associated morbidities. METHODS: In a retrospective pair-matched analysis in a 1:1 ratio, 116 patients after LT were assessed with regards to benefits and risks of abdominal drainage under immunosuppression, respecting model for end-stage liver disease (MELD), age, and gender. RESULTS: The indications for LT were comparable between the drain and the no-drain group. There was an increased rate of early bile leakage in patients with abdominal drainage (13.8 vs. 1.7%, p = 0.032). In addition, a significantly higher incidence of infections requiring antibiotic therapy was observed in the drain group (63.8 vs. 39.7%, p = 0.015). The contribution of drains as a diagnostic tool was marginal, as in the drain group, other diagnostic tools than the drain itself confirmed 50% of all early bile leakages and 60% of postoperative hemorrhages. Overall, there was no difference regarding the incidence of incisional hernia after LT (8.6 vs. 10.3%, p = 1.000), length of hospital stay (22.9 ± 18.7 vs. 18.6 ± 18.6 days, p = 0.215), and 1- and 5-year patient (p = 0.981) and graft survival (p = 0.092). CONCLUSIONS: Equal results can be achieved with or without an abdominal drain in recipients with whole-liver grafts in spite of an increased risk of postoperative infection and biliary leakage in the former group. A benefit of AD as a diagnostic tool could not be demonstrated.
Assuntos
Drenagem/métodos , Transplante de Fígado/métodos , Hemorragia Pós-Operatória/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Doadores de Tecidos , Adulto , Estudos de Casos e Controles , Bases de Dados Factuais , Drenagem/efeitos adversos , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Falência Hepática/mortalidade , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Induction therapy with depleting antibodies in the setting of liver transplantation (LT) is discussed controversially to this day. The rabbit antithymocyteglobulin (ATG) Thymoglobulin (rATG) was introduced as early as 1984 and was frequently used as a standard regime for induction therapy after LT. There are no public reports characterizing Grafalon (ATG-F), a novel ATG, as an induction agent after LT. Objectives: The aim of this observational non-interventional study was to investigate the safety and efficacy of Grafalon induction therapy and characterize its clinical effects in the setting of LT. Methods: A cohort of 80 patients undergoing deceased donor LT at the Medical University of Vienna and receiving Grafalon as part of the clinical standard immunosuppressive regimen was prospectively included between March 2021 and November 2022. Patients were monitored closely for leukocytopenia and thrombocytopenia during the first postoperative week and followed up for incidence and severity of biopsy-proven acute rejection (BPAR), overall survival, and bacterial infections in the first year after LT. Results: The incidences of thrombocytopenia and leukocytopenia following Grafalon treatment peaked on postoperative day four, with 64% and 31%, respectively. However, there were no cases of severe leukocytopenia after the first postoperative week. Induction therapy with Grafalon resulted in a rate of localized bacterial infections and bacteremia of 28% and 21%, respectively. The rate of BPAR was 12.5% in the first year after LT; the one-year survival rate in this cohort was 90%. Conclusions: Overall, this study provides evidence of the safety and efficacy of Grafalon as an induction agent. Further studies investigating the potential long-term effects of Grafalon, as well as comparison studies with different immunosuppressive regimens, are needed in order to draw further conclusions.
RESUMO
Background: Platelets were shown to be relevant for liver regeneration. In particular, platelet-stored serotonin (5-HT) proved to be a pro-regenerative factor in this process. The present study aimed to investigate the perioperative course of 5-HT and evaluate associations with patient and graft outcomes after othotopic liver transplantation (OLT). Methods: 5-HT was quantified in plasma and serum of 44 OLT recipients perioperatively, and in their respective donors. Olthoff's criteria for early allograft dysfunction (EAD) were used to evaluate postoperative outcomes. Results: Patients with higher donor intra-platelet 5-HT per platelet (IP 5-HT PP) values had significantly lower postoperative transaminases (ASAT POD1: p = 0.006, ASAT POD5: p = 0.006, ASAT POD10: p = 0.02, ALAT POD1: p = 0.034, ALAT POD5: p = 0.017, ALAT POD10: p = 0.04). No significant differences were seen between postoperative 5-HT values and the occurrence of EAD. A tendency was measured that donor IP 5-HT PP is lower in donor-recipient pairs that developed EAD (p = 0.07). Conclusions: Donor IP 5-HT PP might be linked to the postoperative development of EAD after OLT, as higher donor levels are correlated with a more favorable postoperative course of transaminases. Further studies with larger cohorts are needed to validate these findings.
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Donor criteria for liver grafts have been expanded because of organ shortage. Currently, no exact definitions for extended donor grafts have been established. The aim of this study was to analyze the impact of donor-specific risk factors, independent of recipient characteristics. In collaboration with Eurotransplant and European Liver Transplant Register, solely donor-specific parameters were correlated with 1-year survival following liver transplantation. Analyses of 4701 donors between 2000 and 2005 resulted in the development of a nomogram to estimate graft survival for available grafts. Predictions by nomogram were compared to those by Donor Risk Index (DRI). In the multivariate analysis, cold ischemic time (CIT), highest sodium, cause of donor death, γ-glutamyl transferase (γ-GT), and donor sex (female) were statistically significant factors for 3 months; CIT, γ-GT, and cause of donor death for 12-month survival. The median DRI of this study population was 1.45 (Q1: 1.17; Q3: 1.67). The agreement between the nomogram and DRI was weak (kappa = 0.23). Several donor-specific risk factors were identified for early survival after liver transplantation. The provided nomogram will support quick organ quality assessment. Nevertheless, this study showed the difficulties of determining an exact definition of extended criteria donors.
Assuntos
Transplante de Fígado/métodos , Transplante de Fígado/normas , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Adulto , Isquemia Fria , Europa (Continente) , Feminino , Sobrevivência de Enxerto , Humanos , Falência Hepática/mortalidade , Falência Hepática/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Listas de Espera , gama-Glutamiltransferase/metabolismoRESUMO
It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.
Assuntos
Transplante de Fígado/métodos , Reperfusão/métodos , Europa (Continente)/epidemiologia , Artéria Hepática/fisiologia , Humanos , Circulação Hepática/fisiologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Veia Porta/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reperfusão/efeitos adversos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The predictive value of MELD score for post-transplant survival has been under constant debate since its implementation in 2001. Aim of this study was to assess the impact of alterations in MELD score throughout waiting time (WT) on post-transplant survival. A single-centre retrospective analysis of 1125 consecutive patients listed for liver transplantation between 1997 and 2009 was performed. The impact of MELD score and dynamic changes in MELD score (DeltaMELD), as well as age, sex, year of listing and WT were evaluated on waiting list mortality and post-transplant survival. In this cohort, 539 (60%) patients were transplanted, 223 (25%) died on list and 142 (15%) were removed from the waiting list during WT. One-, three- and five-year survival after liver transplantation were 83%, 78% and 76% respectively. DeltaMELD as a continuous variable proved to be the only significant risk factor for overall survival after liver transplantation (hazard ratio (HR): 1.06, 95% confidence interval (CI) 1.02-1.1, P = 0.013). The highest risk of post-transplant death could be defined for patients with a DeltaMELD > 10 (HR: 4.87, 95% CI 2.09-11.35, P < 0.0001). In addition, DeltaMELD as well as MELD at listing showed a significant impact on waiting list mortality. DeltaMELD may provide an easy evaluation tool to identify patients on the liver transplant waiting list with a high mortality risk after transplantation in the current setting. Temporarily withholding and re-evaluating these patients might improve overall outcome after liver transplantation.