Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.

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Background and aims Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases. Methods We have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of these organoid models were characterized by analyzing AAT protein secretion and intracellular aggregation in MZ and ZZ genotypes as well as SERPINA1 expression in differentiated cultures. Results Transcriptional analysis of differentiated organoid cultures by RNA-Seq showed hepatocyte-specific gene expression profile. Genes, such as ALB, APOB, CYP3A4 and SERPINA1, were validated and confirmed through quantitative-PCR analysis. The organoids from MZ and ZZ cases showed intracellular aggregation and lower secretion of AAT protein, and lower expression of ALB and APOB, as typically seen in hepatocytes from Z-AAT deficiency patients. Furthermore, organoids responded to external stimulus. Treatment with oncostatin M, a well-known inducer of SERPINA1, increased expression of the full-length transcripts (AAT-1C) as well as the short transcript of AAT (AAT-ST1C4). Conclusions Liver organoid model recapitulates the key features of Z-AAT deficiency and provides a useful tool for disease modeling.

Background. One method for increasing the donor pool for orthotopic liver transplantations (OLTs) is to use uncontrolled donation after circulation death (uDCDs). Methods. From January 2006 to December 2016, we performed 75 OLTs using uDCD livers. The control group comprised a sample of 265 OLTs using livers of donations after brain death (DBDs). A comparative study was performed. Results. Of 256 potential uDCD donors cannulated, 75 (29.3%) livers were accepted for OLT. The amount of hemoderivatives transfused was significantly higher in the uDCD group. The rate of primary nonfunction was also significantly higher (P = 0.031) in uDCD recipients (8%) than DBD recipients (1.5%). The overall rate of biliary complications was significantly higher (P = 0.001) in uDCD recipients (23 cases, 30.6%) than DBD recipients (28 cases, 10.6%). In the uDCD group, 1-, 3-, and 5-year patient survival rates were 82.7%, 73%, and 71.5%, respectively; in the DBD group, they were 89%, 83.7%, and 78.8%, respectively (P = 0.180). In the uDCD group, 1-, 3-, and 5-year graft survival rates were 73.3%, 65.1%, and 63.6%, respectively; in the DBD group, they were 87.1%, 81.9%, and 76.5%, respectively (P = 0.013). Multivariate analysis showed that independent risk factors for patient and graft survival were intraoperative transfusion of >6 units of packed red blood cell concentrates and recipients who were older than 60 years. Conclusions. Although graft survival is significantly lower using uDCD livers, 5-year patient survival in recipients of DBD and uDCD livers is similar. After careful selection, the livers of uDCD can be selectively used for OLT.

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AIMTo analyse the impact of octogenarian donors in liver transplantation.METHODSWe present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ2 test. Comparison of quantitative variables was made by t-test. Graft and patient survivals were estimated using the Kaplan-Meier method.RESULTSOne, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts (P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts (P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient (P = 0.657) and graft (P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative bilirubin.CONCLUSIONThe standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit stay < 3 d, CIT < 9 h, absence of atherosclerosis in the hepatic and gastroduodenal arteries, and no relevant histological alterations in the pre-transplant biopsy, such as fibrosis, hepatitis, cholestasis or macrosteatosis > 30%.

We examined intraepithelial lymphocytes (IELs)

Background Graft primary non‐function (PNF) is the most severe complication after orthotopic liver transplantation (OLT) and is frequently associated with livers from uncontrolled circulatory death (uDCD). Methods We reviewed retrospectively the incidence, risk factors, and outcome of patients showing PNF after receiving uDCD liver grafts. The series comprises 75 OLT performed during 11 years. Results The incidence of PNF using uDCD livers was 8%. We compared patients who developed PNF (n = 6) vs. patients without PNF (n = 69). Mean pump flow of donors during normothermic regional perfusion (NRP) was significantly lower in PNF (p = .032). Day 1 post‐OLT levels of transaminases and the incidence of renal complications and postoperative mortality were also significantly higher in the PNF group, but 5‐year patient survival was similar in both groups (66.7% in PNF and 68.5% in non‐PNF). All PNF patients underwent re‐OLT, and 2 died. PNF incidence has decreased in the last 5‐years. Binary logistic regression analysis confirmed final ALT value >4 times the normal value as risk factor for PNF, and median donor pump flow >3700 ml/min as protective effect. Conclusions Adequate donor pump flow during NRP was a protective.