Identification of peripheral CD154+ T-cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

This study aimed to analyse different surface antigens on T-cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multiparametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1-year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T-cells, HLA mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T-cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by FACS analysis. A high percentage of CD4+CD154+ T-cells (p=0.001) and a low percentage of CD8+CD154+ T-cells (p=0.002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (p=0.001) and CD8+CD154+ T-cells (p=0.002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T-cell subsets were significantly higher in ACR, despite variations compared to pre-transplant. These findings support the selection of candidates for LT based on the pre-transplant percentages of CD4+CD154+ and CD8+CD154+ T-cells in parallel with other transplant factors. PMID: 33025...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research

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CONCLUSION: DAAs are effective and safe in the treatment of recurrent HCV infection in LT recipients with history of HCC. Relapse to pre- and post-LT DAA therapy is associated with post-transplantation HCC recurrence. PMID: 33033569 [PubMed]
Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
AbstractBackground and objective The main objective was to evaluate the impact of Hepatitis C Virus treatment with direct-acting antiviral agents on tacrolimus blood levels in recipients of kidney and heart allografts.Method We analysed Hepatitis C Virus infected adult patients who received tacrolimus as immunosuppressive maintenance therapy and received direct-acting antiviral agents treatment in a tertiary hospital with solid transplant multidisciplinary program in Madrid, Spain. Liver and renal function, tacrolimus dose and blood levels were analysed before and 12  weeks after the end of treatment.Results We identi...
Source: International Journal of Clinical Pharmacy - Category: Drugs & Pharmacology Source Type: research
Regulatory immune cell-based therapy has emerged as a promising strategy to promote immunosuppression withdrawal without jeopardizing allograft function. Regulatory dendritic cells (DCregs) are a subset of hematopoietic progenitor cells that have been shown to downregulate alloimmune response and prolong allograft survival in animal models. We investigate the safety and immunomodulatory effect of human donor-derived DCreg adoptive transfer in living donor liver transplantation.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Transplantation and Tissue Engineering Source Type: research
Hepatic steatosis (HS) is a key factor predicting postoperative allograft function and determining overall discard in liver transplantation (LT). The potential of normothermic machine perfusion (NMP) as an adjunct to LT has been a focus of recent scrutiny due to its ability to attenuate ischemia reperfusion injuries (IRI) and maintain graft functionality. The nuclear-factor-erythroid 2-related-factor-2 (Nrf2) axis may be an important IRI mediator in HS. We aimed to characterize and compare Nrf2 expression profiles between lean and steatotic tissue undergoing NMP.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Transplantation and tissue engineering Source Type: research
Conclusions. These results may help advance the current state of knowledge about risk factors for GVHD development following intestinal transplantation.
Source: Transplantation - Category: Transplant Surgery Tags: Original Clinical Science—General Source Type: research
Conclusions. Cibinetide reduced the initial transplantation–related severe inflammation and delayed the subsequent alloreactivity. Cibinetide, in combination with low-dose tacrolimus, could significantly improve long-term graft survival in allogeneic PITx.
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science—General Source Type: research
CONCLUSIONS: Our data suggest that minimization of CNI and conversion of CNI to mTOR inhibitors along with judicious use of prophylactic steroids may allow for the safe use of ICIs in SOT recipients with advanced cSCC. Short-term efficacy appears promising but prospective studies with further follow-up and a standardized protocol for prophylactic steroids are needed. IMPLICATIONS FOR PRACTICE: Solid organ transplant (SOT) recipients are at increased risk of developing malignancy due to long-term post-transplant immunosuppression. Although immune checkpoint inhibitors (ICI) are increasingly shown to be successful in tr...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT7) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the binary EAD (AUROC=0.68) definition and Model for Early Allograft Function (MEAF, AUROC=0.70) in the single-center derivation cohort (DC, n=2008). We sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF.
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
CONCLUSIONS Our experience shows that the ABO-i LDLT protocol of lowered rituximab combined with pre-transplant sessions of plasmapheresis and a quadruple immunosuppressive regimen can be effective in chronic liver failure patients with clinical urgency in the absence of an ABO-compatible donor. Fast-tracking the use of ABO-i LDLT is feasible in patients with an acute liver failure (ALF) and can safely increase the donor liver pool, with an acceptable outcome. PMID: 32943600 [PubMed - in process]
Source: Annals of Transplantation - Category: Transplant Surgery Authors: Tags: Ann Transplant Source Type: research
Semin Liver Dis DOI: 10.1055/s-0040-1709492Liver transplantation (LT) is an optimal treatment option for early-stage unresectable hepatocellular carcinoma (HCC) in patients with cirrhosis as it provides a treatment for underlying liver disease as well as a decreased incidence of recurrent cancer compared with alternative treatment strategies. A primary barrier to LT for HCC is the critical shortage of available liver allografts. The system of prioritization and access to deceased donor transplantation for patient with HCC in the United States has continued to evolve, while variable approaches including no additional priori...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
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