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BACKGROUND & AIM: We aimed to assess long-term outcome after transplantation of HOPE-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of a HOPE-treated liver transplanted between January 2012 and December 2021. Analyses were stratified for brain-dead (DBD) and circulatory-dead (DCD) donor livers, sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischemic cholangiopathy (IC). RESULTS: We report on 1202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low-risk (10%), 186 as high-risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival for DBD and DCD was 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (logrank p=0.003). Within DBD and DCD-strata, death-censored graft survival was similar among risk groups (logrank p=0.26, p=0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE-treatment has now reached IDEAL-D stage 4, which further supports the implementation of HOPE in routine clinical practice. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of HOPE-treatment of DCD and DBD liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomized controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE-treatment has now reached the final IDEAL-D Stage 4, which further supports the implementation of HOPE in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320.
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To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.
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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.
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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
Although aortohepatic conduits (AHCs) provide an effective technique for arterialization in liver transplantation (LT) when the native recipient artery is unusable, various publications report higher occlusion rates and impaired outcome compared to conventional anastomoses. This systematic review and meta-analysis investigates the published evidence of outcome and risk of AHCs in LT using bibliographic databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Primary and secondary outcome were artery occlusion as well as graft and patient survival. Twenty-three retrospective studies were identified with a total of 22 113 patients with LT, of whom 1900 patients (9%) received an AHC. An AHC was used in 33% of retransplantations. Early artery occlusion occurred in 7% (3%-16%) of patients with AHCs, compared to 2% (1%-3%) without conduit (OR 3.70; 1.63-8.38; P = .001). The retransplantation rate after occlusion was not significantly different in both groups (OR 1.46; 0.67-3.18; P = .35). Graft (HR 1.38; 1.17-1.63; P < .001) and patient (HR 1.57; 1.12-2.20; P = .009) survival was significantly lower in the AHC compared to the nonconduit group. In contrast, graft survival in retransplantations was comparable (HR 1.00; 0.82-1.22; P = .986). Although AHCs provide an important rescue option, when regular revascularization is not feasible during LT, transplant surgeons should be alert of the potential risk of inferior outcome.
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Doença Hepática Terminal/cirurgia , Artéria Hepática/cirurgia , Artéria Ilíaca/transplante , Transplante de Fígado/efeitos adversos , Trombose/terapia , Humanos , Prognóstico , Estudos Retrospectivos , Trombose/etiologia , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos VascularesRESUMO
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.
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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
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.
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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
Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long-term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.
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Abstinência de Álcool , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Consumo de Bebidas Alcoólicas , Biomarcadores , Carboidratos/química , Progressão da Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Hepatopatias Alcoólicas/terapia , Masculino , Seleção de Pacientes , Recidiva , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Fatores de Tempo , Transferrina/análogos & derivados , Transferrina/química , Transferrina/uso terapêutico , Resultado do Tratamento , Listas de EsperaRESUMO
BACKGROUND & AIMS: Various types of liver disease are associated with an increased prevalence of colorectal adenomas. We investigated whether cirrhosis is a risk factor for colorectal neoplasia by analyzing colonoscopy findings from 2 cohorts of patients awaiting liver transplantation. METHODS: We performed a retrospective analysis to compare findings from colorectal cancer screenings of 567 adult patients with cirrhosis placed on the waitlist for liver transplantation with those from controls (matched for age, sex, body mass index, smoking, and diabetes). Rates of adenoma and advanced adenoma detection were adjusted owing to differences in rates of polypectomies performed in the 2 cohorts. RESULTS: Adenomas were detected in a significantly higher percentage of patients with cirrhosis (29.3%) than in controls (21.5%) (P = .0057; relative risk [RR], 1.36; 95% confidence interval [CI], 1.09-1.69); and patients with cirrhosis had a higher rate of advanced adenoma detection than controls (13.9% vs 7.7%; P = .0015; relative risk, 1.82; 95% CI, 1.25-2.64). A greater percentage of patients with alcoholic cirrhosis had neoplasias (34.3%) than controls (25.3%; P = .0350; RR, 1.36), and rates of advanced adenoma detection were 16.7% vs 10.2% (P = .0409; RR, 1.63). Adenomas were detected in 27.8% of patients with viral cirrhosis vs 15.9% of controls (P = .0061; RR, 1.74), with rates of advanced adenoma detection of 13.6% vs 5.0% (P = .0041; RR, 2.73). Similar proportions of patients with cirrhosis of other etiologies and controls were found to have colorectal neoplasias. CONCLUSIONS: Based on a retrospective analysis of colonoscopy findings from patients awaiting liver transplantation, those with alcoholic or viral cirrhosis are at higher risk of developing colorectal neoplasia and should be considered for earlier colonoscopy examination.
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Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Cirrose Hepática/complicações , Estudos de Coortes , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
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.
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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
The influence of recipient gender on urological complications including vesicoureteral reflux (VUR) after renal transplantation has not yet been established. In this study, post-transplantation voiding cystourethrography and ultrasonography were used to evaluate the upper and lower urinary tract in 598 consecutive renal transplant recipients. Our cohort included 209 females and 389 males, respectively. Gender-specific urological complications and potential confounders were analyzed in relation to long-term allograft outcomes. Postoperative urinary retention occurred more frequently in men (P = 0.004). Urinary tract infections (UTIs) were diagnosed more frequently in women after transplantation (P = 0.05). In a multivariate analysis, gender was not a risk factor for VUR [HR, 1.35 (CI, 0.90-1.96); P = 0.14]. VUR rates were influenced by the surgeon's experience level at the time of transplantation [HR, 0.59 (CI, 0.40-0.87); P = 0.008]. No gender-specific differences were seen for ureteral stenosis, leakage, hydronephrosis, death-censored graft or patient survival, and long-term allograft function. Donor/recipient gender mismatch had no impact on postoperative complication rates. In conclusion, male transplant recipients are at risk for developing postoperative urinary retention, whereas female patients more likely develop UTIs. Surgeon's experience level is a risk factor for developing VUR.
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Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etiologia , Refluxo Vesicoureteral/etiologia , Adulto , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Caracteres Sexuais , Retenção Urinária/etiologia , Infecções Urinárias/etiologiaRESUMO
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.
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Peritoneal dialysis (PD) has wide clinical range since die 70ies. Clinical data report a significantly higher 2 year survival rate for PD compared to patients treated with hemodialysis. Nevertheless, currently only about 10 % of patients suffering from end-stage renal disease are treated with PD. Long-term function of the catheter is based on patient's compliance as well as optimal surgical catheter implantation. Beside the classic "open" surgical approach by mini laparotomy new minimal invasive techniques of catheter implantation were developed during the last years. Advantages of laparoscopic techniques are the possibility for combined intraperitoneal procedures and optimal placement of the catheter. Most of surgery-related complications are caused by leakage or migration, infection is very rare. Several studies did not find an advantage of minimal invasive procedures regarding complications.This review should give an overview on currently established surgical techniques for PD-catheter implantation.
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Cateteres de Demora , Falência Renal Crônica/terapia , Laparoscopia , Procedimentos Cirúrgicos Minimamente Invasivos , Diálise Peritoneal Ambulatorial Contínua/métodos , Áustria , Contraindicações , Humanos , Falência Renal Crônica/mortalidade , Diálise Peritoneal Ambulatorial Contínua/mortalidade , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.
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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.
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Falência Hepática/mortalidade , Falência Hepática/terapia , Transplante de Fígado/métodos , Adulto , Idoso , Algoritmos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaRESUMO
Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight patients with non-alcoholic fatty liver disease and relative hypoleptinemia independent of its anorexic action. In rodents, leptin signaling in the brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretion and reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlled crossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. A single metreleptin injection stimulated hepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted, lean men (n = 13, age range 20-38 years) but failed to do so in metabolically healthy liver transplant recipients (n = 9, age range 26-62 years) who represent a model for hepatic denervation. In an independent cohort of lean men (n = 10, age range 23-31 years), vagal stimulation by modified sham feeding replicated the effects of metreleptin on VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis.
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Leptina , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Adulto Jovem , Adulto , Leptina/farmacologia , Leptina/metabolismo , Lipoproteínas VLDL/metabolismo , Triglicerídeos/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Nervo Vago/metabolismoRESUMO
BACKGROUND: Within the last decade numerous attempts have been reported in order to expand the donor pool and alleviate organ shortage in the setting of liver transplantation. Aim of this blinded randomized controlled trial was to evaluate the effect of donor steroid pretreatment on outcomes after liver transplantation. METHODS: We performed an international, multi-center double-blinded randomized placebo controlled trial. Donors received 1000 mg methylprednisone or placebo before organ procurement. Primary endpoint were patient and graft survival. Secondary end points were rate of BPAR and liver functions trajectories after transplantation. Follow up was 10 years. RESULTS: There was no effect of steroid pretreatment vs. placebo on overall patient survival (50% vs. 46%, p = n.s.) as well as graft survival (47% vs. 51%, p= n.s.). Further donor steroid pretreatment did not alter the rate of biopsy proven acute rejections (34% steroid group vs. 36% placebo, p = n.s.). Evaluating short term and long term graft function, steroid pretreatment had minor effect on immediate liver function trajectories within the first 2 weeks after transplantation. This was not seen in long-term follow up. CONCLUSION: In conclusion we found no evidence that donor steroid pretreatment translates in improved outcomes after liver transplantation.
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Rejeição de Enxerto , Transplante de Rim , Aloenxertos , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Fígado , Esteroides , Doadores de Tecidos , Resultado do TratamentoRESUMO
BACKGROUND: The Milan criteria are recommended to select hepatocellular carcinoma (HCC) patients for liver transplantation (LT). The utility of other selection criteria, such as the alpha-fetoprotein-adjusted-to-HCC-size (AFP-UTS) criteria, is still unclear. OBJECTIVE: We investigated, in HCC patients who underwent LT, the survival and the recurrence after LT according to AFP-UTS and Milan criteria, the impact of early recurrence and the correlation between radiological and pathological staging. METHODS: Adult HCC patients undergoing deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed. RESULTS: Among 166 patients included, the number of patients who fulfilled Milan or AFP-UTS criteria was the same (139 [84%] each), although not all of them were the same individuals; 127 patients (77%) fulfilled both Milan and AFP-UTS criteria. Median overall survival of patients within AFP-UTS was 126.9 versus 34.2 months outside AFP-UTS (5-year survival rate 71% vs. 43%; p = 0.104). The 5-year recurrence rate was significantly lower in patients fulfilling the AFP-UTS criteria (18%) than in those exceeding AFP-UTS (64%; p < 0.001). Of the 139 patients within Milan criteria on imaging, 24 (17%) had microvascular invasion and 47 (34%) were outside Milan according to explant histology. Early recurrence correlated with AFP-UTS and was associated with dismal survival (median overall survival 17.2 vs. 122.1 months, p = 0.002). CONCLUSIONS: The overall survival of patients within AFP-UTS criteria was favourable with a 5-year survival rate above 70%. Early recurrence is associated with worse survival after LT. The AFP-UTS criteria may be more suitable to exclude patients at high risk of (early) recurrence than Milan criteria.
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Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Carga TumoralAssuntos
Hepatectomia/métodos , Fígado/patologia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Causas de Morte , Colangiocarcinoma/cirurgia , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Mortalidade Hospitalar , Humanos , Hipertrofia/etiologia , Hipertrofia/prevenção & controle , Ligadura/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Veia Porta/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Radical surgery with lymphadenectomy offers the best chance of curing esophageal cancer, but it carries considerable risks. Generally, the resected esophagus is replaced with a gastric tube. Rupture of the gastric tube staple line is a rare but serious surgical complication. One unresolved issue is whether oversewing of the longitudinal gastric staple line is necessary to avoid staple line rupture or insufficiency. PATIENTS AND METHODS: Between 2000 and February 2008, 199 patients underwent esophageal resection for cancer or perforation at the Vienna General Hospital, Medical University of Vienna. Data were collected prospectively. Of these patients, 151 (75.9%) underwent reconstruction by pulling up a gastric tube. These comprised the study population. In 83 patients (55.0%) the longitudinal gastric staple line was not oversewn (group A). In 68 patients (45.0%) the staple line was reinforced by invaginating sutures (group B). RESULTS: The mean age of the patients was 62.0 +/- 10.6 years (median: 63.1 years). Males comprised 75.5% of the population. Adenocarcinoma was diagnosed in 77 patients (51.0%), 63 patients (41.7%) suffered from a squamous cell carcinoma, 10 patients (6.6%) had esophageal perforation, and in 1 patient (0.7%) a gastrointestinal stromal tumor was diagnosed. In group A, a leak within the staple line was observed in 4 of 83 patients (4.9%). No leak was found in group B (p = 0.09). Major surgical complications included anastomotic leakage (21 patients; 13.9%), gastric tip necrosis (3 patients; 2%), postoperative ileus (3 patients; 2.0%) and chylothorax (7 patients; 4.6%). Two major intraoperative complications (1.3%) were splenic injury and aortic bleeding. CONCLUSION: A remarkable but not statistically significant difference was found regarding staple line rupture between study groups. However, all leaks were seen in patients without a staple line suture.
Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Deiscência da Ferida Operatória/prevenção & controle , Técnicas de Sutura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ruptura Espontânea , Grampeamento Cirúrgico , Resultado do TratamentoRESUMO
BACKGROUND: Serum C-reactive protein (CRP) is a prognostic factor for overall survival (OS) and recurrence of hepatocellular carcinoma (HCC) in patients treated with resection or non-surgical treatment. Here, we investigated the association of elevated CRP (≥1 vs. <1 mg/dL) with (i) recurrence of HCC and (ii) OS after liver transplantation (LT). METHODS: Adult HCC patients undergoing orthotopic deceased donor LT at the Medical University of Vienna between 1997 and 2014 were retrospectively analysed. RESULTS: Among 216 patients included, 132 (61.1%) were transplanted within the Milan criteria and forty-two patients (19.4%) had microvascular invasion on explant histology. Seventy patients (32.4%) showed elevated CRP (≥ 1 mg/dL). On multivariate analysis, a CRP ≥ 1 mg/dL was an independent risk factor for HCC recurrence with a 5-year recurrence rate of 27.4% vs. 16.4% (HR 2.33; 95% CI 1.13-4.83; p = 0.022). OS was similar in patients with normal vs. elevated CRP levels. CONCLUSIONS: Elevated serum CRP is associated with HCC recurrence after LT and may be a marker for more aggressive tumor biology. Future studies should evaluate whether patients with elevated pre-transplant CRP levels benefit from closer monitoring for HCC recurrence.