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See detailPreserving the morphology and evaluating the quality of liver grafts by hypothermic machine perfusion: A proof-of-concept study using discarded human livers.
Monbaliu, Diethard; Liu, Qiang; Libbrecht, Louis et al

in Liver Transplantation (2012), 18(12), 1495-507

The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk ... [more ▼]

The wider use of livers from expanded criteria donors and donation after circulatory death donors may help to improve access to liver transplantation. A prerequisite for safely using these higher risk livers is the development of objective criteria for assessing their condition before transplantation. Compared to simple cold storage, hypothermic machine perfusion (HMP) provides a unique window for evaluating liver grafts between procurement and transplantation. In this proof-of-concept study, we tested basic parameters during HMP that may reflect the condition of human liver grafts, and we assessed their morphology after prolonged HMP. Seventeen discarded human livers were machine-perfused. Eleven livers were nontransplantable (major absolute contraindications and severe macrovesicular steatosis in the majority of the cases). Six livers were found in retrospect to be transplantable but could not be allocated and served as controls. Metabolic parameters (pH, lactate, partial pressure of oxygen, and partial pressure of carbon dioxide), enzyme release in the perfusate [aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)], and arterial/portal resistances were monitored during HMP. Nontransplantable livers released more AST and LDH than transplantable livers. In contrast, arterial/portal vascular resistances and metabolic profiles did not differ between the 2 groups. Morphologically, transplantable livers remained well preserved after 24 hours of HMP. In conclusion, HMP preserves the morphology of human livers for prolonged periods. A biochemical analysis of the perfusate provides information reflecting the extent of the injury endured. Liver Transpl, 2012. (c) 2012 AASLD. [less ▲]

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See detailLiver transplantation for unresectable hepatocellular carcinoma in normal livers.
Mergental, Hynek; Adam, Rene; Ericzon, Bo-Goran et al

in Journal of Hepatology (2012), 57(2), 297-305

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for ... [more ▼]

BACKGROUND & AIMS: The role of liver transplantation in the treatment of hepatocellular carcinoma in livers without fibrosis/cirrhosis (NC-HCC) is unclear. We aimed to determine selection criteria for liver transplantation in patients with NC-HCC. METHODS: Using the European Liver Transplant Registry, we identified 105 patients who underwent liver transplantation for unresectable NC-HCC. Detailed information about patient, tumor characteristics, and survival was obtained from the transplant centers. Variables associated with survival were identified using univariate and multivariate statistical analyses. RESULTS: Liver transplantation was primary treatment in 62 patients and rescue therapy for intrahepatic recurrences after liver resection in 43. Median number of tumors was 3 (range 1-7) and median tumor size 8cm (range 0.5-30). One- and 5-year overall and tumor-free survival rates were 84% and 49% and 76% and 43%, respectively. Macrovascular invasion (HR 2.55, 95% CI 1.34 to 4.86), lymph node involvement (HR 2.60, 95% CI 1.28 to 5.28), and time interval between liver resection and transplantation <12months (HR 2.12, 95% CI 0.96 to 4.67) were independently associated with survival. Five-year survival in patients without macrovascular invasion or lymph node involvement was 59% (95% CI 47-70%). Tumor size was not associated with survival. CONCLUSIONS: This is the largest reported series of patients transplanted for NC-HCC. Selection of patients without macrovascular invasion or lymph node involvement, or patients 12months after previous liver resection, can result in 5-year survival rates of 59%. In contrast to HCC in cirrhosis, tumor size is not a predictor of post-transplant survival in NC-HCC. [less ▲]

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See detailEfficacy and safety of maribavir dosed at 100 mg orally twice daily for the prevention of cytomegalovirus disease in liver transplant recipients: a randomized, double-blind, multicenter controlled trial.
Winston, D. J.; Saliba, F.; Blumberg, E. et al

in American Journal of Transplantation (2012), 12(11), 3021-30

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter ... [more ▼]

Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease. [less ▲]

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See detailMachine perfusion versus cold storage for the preservation of kidneys from donors ≥ years allocated in the Eurotransplant Senior Programme
GALLINAT, Anja; MOERS, Cyril; TRECKMANN, Jürgen et al

in Nephrology Dialysis Transplantation (2012), 27

Background. In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥65 years are preferentially allocated locally and transplanted into patients aged ≥65 years on dialysis. The purpose of ... [more ▼]

Background. In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥65 years are preferentially allocated locally and transplanted into patients aged ≥65 years on dialysis. The purpose of this study was to analyse whether the results of transplantation in the ESP can be improved by preservation of organs by hypothermic machine perfusion (MP) compared with simple cold storage (CS). Methods. Overall, 85 deceased heart-beating donors ≥65 years of age were included in this analysis with follow-up until 1 year post-transplant. For each donor, one kidney was randomly assigned to preservation by CS and the contralateral kidney to MP from organ procurement until transplantation. Delayed graft function (DGF), primary non-function (PNF) and 1-year patient and graft survival rates were evaluated as primary and secondary endpoints. Results. The median recipient age was 66 years in both groups and the median cold ischaemia time was 11 h for MP and 10.5 h for CS (P = 0.69). The DGF rate was 29.4% for MP and 34.1% for CS (P = 0.58). Only extended duration of cold ischaemia time was an independent risk factor for the development of DGF (odds ratio 1.2, P < 0.0001). PNF was significantly reduced (3.5% MP versus 12.9% CS, P = 0.02). The 1-year patient and graft survival rates were similar for MP and CS (94% versus 95% and 89 versus 81%, P > 0.05). The 1-year graft survival rate was significantly improved after MP in recipients who developed DGF (84% MP versus 48% CS, P = 0.01). Conclusions. Continuous pulsatile hypothermic MP for kidneys from donors aged ≥65 years can reduce the rate of never-functioning kidneys and improve the 1-year graft survival rate of kidneys with DGF. In this small cohort, the known advantage of MP for the reduction of DGF could not be confirmed, possibly due to relatively short cold ischaemia times. [less ▲]

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See detailMachine perfusion in clinical trials : "machine vs. solution effects"
Treckmann, Jürgen; Moers, Cyril; Smits, Jacqueline M et al

in Transplant International (2012), 25

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See detailKidney donation after circulatory death in a country with a high number of brain dead donors: 10 -year experience in Belgium
Jochmans, Ina; Darius, Tom; Kuypers, Dirk et al

in Transplant International (2012), 25

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its ... [more ▼]

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five-year patient/graft survival was assessed using Kaplan–Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five-year patient and death-censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine-tryptophan-ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused. Transplant International ISSN 0934-0874 ª [less ▲]

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See detailLIVER TRANSPLANTATION FROM DONATION AFTER CARDIOCIRCULATORY DEATH (DCD) DONORS: BELGIAN EXPERIENCE 2003-2009
DE ROOVER, Arnaud ULg; Le Dinh, Hieu ULg; Cicarelli, Olga et al

in Transplant International (2011, September), 24(2), 84-84

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See detailBELGIAN EXPERIENCE OF DCD KIDNEY TRANSPLANTATION
Darius, Tom; Jochmans, Ina; Ledinh, Hieu et al

in Transplant International (2011, September), 24(2), 43-44

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See detailMULTICENTER BELGIAN SURVEY ON DONOR MORBIDITY AND MORTALITY IN ADULT-TO-ADULT LIVING DONOR LIVER TRANSPLANTATION
Troisi, Roberto I; Vogelaers, Dirk; Lerut, Jan et al

in Transplant International (2011, September), 24(2), 13-13

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See detailMachine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death
Treckmann, Jürgen; Moers, Cyril; Smits, Jacqueline M et al

in Transplant International (2011), 24

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys ... [more ▼]

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heartbeating deceased ECDs – defined according to the United Network of Organ Sharing definition – were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). One-year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1-year graft survival and function in ECD kidneys. [less ▲]

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See detailThe value of machine perfusion perfusate biomakers for predicting kidney transplant outcome
Moers, Cyril; Varnay, Oana C; Van Heurn, Ernest et al

in Transplantation (2010), 90

Background. Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl- -D-glucosaminidase (NAG), and ... [more ▼]

Background. Retrospective evidence suggests that lactate dehydrogenase, aspartate aminotransferase, total glutathione-S-transferase (GST), alanine-aminopeptidase, N-acetyl- -D-glucosaminidase (NAG), and hearttype fatty acid binding protein (H-FABP) measured during kidney machine perfusion (MP) could have predictive value for posttransplant outcome. However, these data may be biased due to organ discard based on biomarker measurements, and previous analyses were not adjusted for likely confounding factors.Noreliable prospective evidence has been available so far. Nevertheless, some centers already use these biomarkers to aid decisions on accepting or discarding a donor kidney. Methods. From 306 deceased-donor kidneys donated after brain death or controlled cardiac death and included in an international randomized controlled trial, these six biomarkers were measured in the MP perfusate. In this unselected prospective data set, we tested whether concentrations were associated with delayed graft function, primary nonfunction, and graft survival. Multivariate regression models investigated whether the biomarkers remained independent predictors when adjusted for relevant confounding factors. Results. GST, NAG, and H-FABP were independent predictors of delayed graft function but not of primary nonfunction and graft survival. Lactate dehydrogenase, aspartate aminotransferase, and alanine-aminopeptidase had no independent prognostic potential for any of the endpoints. Perfusate biomarker concentrations had no relevant correlation with cold ischemic time or renal vascular resistance on the pump. Conclusions. Increased GST, NAG, or H-FABP concentrations during MP are an indication to adjust posttransplant recipient management. However, this study shows for the first time that perfusate biomarker measurements should not lead to kidney discard. Keywords: Machine perfusion, Kidney transplantation, Perfusate biomarkers, Delayed graft function, Graft survival [less ▲]

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See detailLiver transplantation from donation after cardiac death donors: initial Belgian experience 2003-2007.
Detry, Olivier ULg; Donckier, Vincent; Lucidi, Valerio et al

in Transplant International (2010), 23(6), 611-618

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From ... [more ▼]

The Belgian experience with donation after cardiac death (DCD) liver transplantation (LT) was retrospectively reviewed, particularly evaluating patient and graft survivals, and biliary complications. From 2003 to 2007, 58 DCD-LT were performed in Belgium. Mean procurement total warm ischemia time was 25 +/- 2 min (mean +/- SEM). Mean cold ischemia time was 451 +/- 18 min. Mean follow-up was 23 +/- 2.2 months. Post-transplant peak aspartate aminotransminases was 2241 +/- 338 UI/l. Patient survivals at 1 month, 1 and 3 years, were 91.3%, 83.3% and 66.9% respectively. Graft survivals at 1 month, 1 and 3 years, were 84.4%, 72.4% and 48.8% respectively. Two patients (3.4%) developed primary nonfunction. Regarding the biliary complications, seven grafts (12%) were lost because of intrahepatic cholangiopathy, and 12 other patients (20.6%) developed bile duct stenoses requiring endoscopic and/or surgical management. The rate of symptomatic ischemic biliary lesions for grafts surviving more than 3 months was 38% (19/50). Although DCD organ donors may be a source of viable liver grafts, results were inferior to those obtained with donation after brain death LT in this series. Prognostic criteria have to be developed to improve results of DCD-LT. [less ▲]

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See detailLiver transplantation (LT) from donation after cardiac death (DCD) donors: Multicenter Belgian experience 2003-2007
Detry, Olivier ULg; Donckier, Vincent; Lucidi, Valerio et al

in Transplant International (2009, August), 22(S2), 62-234

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See detailTransplantation hépatique à partir de donneurs cadavériques à coeur arrêté: expérience multicentrique belge de 58 cas sur 5 ans
Detry, Olivier ULg; Rahmel, Axel; Donckier, Vincent et al

Conference (2008, October 11)

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See detailOutcome of Patients with Hepatocellular Carcinoma Listed for Liver Transplantation Within the Eurotransplant Allocation System
Adler, Michael; De Pauw, Filip; Vereerstraeten, Pierre et al

in Liver Transplantation (2008), 14

Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor ... [more ▼]

Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor-related variables were evaluated in 226 patients listed primarily for HCC in Belgium, a region where the allocation system is patient-driven, priority being given to sicker patients, based on the Child-Turcotte-Pugh (CTP) score. Intention-to-treat and posttransplantation survival rates at 4 years were 56.5 and 66%, respectively, and overall HCC recurrence rate was 10%. The most significant predictors of failure to receive a transplant in due time were baseline CTP score equal to or above 9 (relative risk [RR] 4.1; confidence interval [CI]: 1.7-9.9) and alpha fetoprotein above 100 ng/mL (RR 3.0; CI: 1.2-7.1). Independent predictors of posttransplantation mortality were age equal to or above 50 years (RR 2.5; CI: 1.0-3.7) and United Network for Organ Sharing pathological tumor nodule metastasis above the Milan criteria (RR 2.1; CI: 1.0-5.9). Predictors of recurrence (10%) were _ fetoprotein above 100 ng/mL (RR 3.2; CI:1.1-10) and vascular involvement of the tumor on the explant (RR 3.6; CI: 1.1-11.3). Assessing the value of the pretransplantation staging by imaging compared to explant pathology revealed 34% accuracy, absence of carcinoma in 8.3%, overstaging in 36.2%, and understaging in 10.4%. Allocation rules for HCC should consider not only tumor characteristics but also the degree of liver impairment. Patients older than 50 years with a stage above the Milan criteria at transplantation have a poorer prognosis after transplantation. [less ▲]

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See detailOne year experience of the Belgian Liver Intestine Comittee (BLIC) intranet database
Lerut, Jan; Roggen, F.; De Hemptinne, Bernard et al

in Acta Gastro-Enterologica Belgica (2001, January), 64(1), 7

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See detailSurveillance clinique de la transplantation : complications chirurgicales
Meurisse, Michel ULg; Pirenne, Jacques; Bonnet, Pierre ULg

in Néphrologie Dialyse Transplantation - Livre de références - ORPADT - Volume 2 (1999)

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See detailCombined Liver - Spleen -small intestine grafting in a rat model: Role of transplanting additional lymphoid tissue on survival.
D'Silva, Milbhor; Pirenne, Jacques; Nakhleh, R. E. et al

in International Surgery (1996), (81), 109-114

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See detailAspects chirurgicaux de la transplantation d'organes
Meurisse, Michel ULg; Pirenne, Jacques; Bonnet, Pierre ULg

in Néphrologie Dialyse Transplantation - Livre de références - ORPADT - Volume 2 (1993)

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See detail"Arterialization", "revascularization" , "rearterialization" - what's in a name?
D'Silva, Milbhor; Pirenne, Jacques; Bonnet, Pierre ULg et al

in Transplant International (1992), (5), 121-122

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