Transplant International最新文献

Cytomegalovirus (CMV) infection poses significant challenges in solid organ transplant (SOT) recipients, impacting graft outcomes, morbidity, and in some cases survival. The ESOT CMV Workshop 2023 convened European experts to discuss current practices and advances in the management of CMV with the aim of improving the quality of life of transplant recipients. Discussions covered crucial areas such as preventive strategies, diagnostic challenges, therapeutic approaches, and the role of cell-mediated immunity (CMI) monitoring. Despite advances, ambiguity persists in optimal CMV management across European transplant centers. Preventive strategies, including universal prophylaxis and pre-emptive therapy, are effective but consensus is lacking with respect to the preferred approach. Diagnostic challenges such as standardization of viral load thresholds and detection of end-organ disease complicate timely intervention. While newer therapies like maribavir hold promise for treating complicated CMV infections, sustaining viral clearance remains a challenge. Integrating CMI monitoring into CMV management could personalize treatment decisions but has limitations in in terms of predictive value and accessibility. Further research is needed to fill these gaps and optimize CMV management. The collaborative efforts, led by the European Society for Organ Transplantation (ESOT), aim to standardize and improve CMV care, ensuring better outcomes for SOT recipients.

HLA molecular matching in solid organ transplantation in the form of eplets, solvent-accessible amino acids or PIRCHE-II has been proposed as a more granular method than HLA matching on the antigen level. While many studies have shown the association between molecular mismatches and de novo donor-specific antibody formation, rejection and graft loss, evidence for prospective molecular matching in allocation is currently lacking, and the actual practical implementation and feasibility of molecular matching remains unclear. In this review the various potential applications of molecular matching in transplantation are discussed, including 1) organ allocation in deceased donor programs, 2) living donor selection, 3) increasing the transplantability of highly sensitized patients and 4) risk stratification to facilitate personalized immunosuppressive management, along with the challenges and gaps in current knowledge regarding these approaches. While clinical application of molecular mismatch analysis in solid organ transplantation holds promise, the fundamentals of HLA-specific antibody biology and epitope-paratope interactions should be further elucidated. This will aid in unraveling the factors that affect the relative immunogenicity of HLA molecular mismatches in order to start using molecular matching in clinical transplantation.

Previous studies have reported comparable oncologic outcome between ABO-incompatible (ABOi) living donor liver transplantation (LDLT) and ABO-compatible (ABOc) LDLT in patients with hepatocellular carcinoma (HCC). We aimed to analyze the relationship between number of therapeutic plasma exchanges (TPE) before LDLT and HCC outcomes in ABOi LDLT. In this single-center retrospective study, 428 adult LDLT recipients with HCC were categorized into three groups according to ABO incompatibility and the number of pretransplant TPE: ABOc (n = 323), ABOi/TPE ≤5 (n = 75), and ABOi/TPE ≥6 (n = 30). The RFS and HCC recurrence rates were compared. Three groups showed similar characteristics in most demographics, pretransplant tumor markers and pathologies. The median initial isoagglutinin (IA) titer was 1:64 (range negative-1:512) in ABOi/TPE ≤5 group and 1:512 (range 1:128-1:4,096) in ABOi/TPE ≥6 group. Five-year RFS was significantly lower (75.7% vs. 72.7% vs. 50.0%, P = 0.005) and HCC recurrence was significantly higher in the ABOi/TPE ≥6 group than in the other groups(16.4% vs. 17.0% vs. 39.4%, P = 0.014). In multivariable Cox regression analysis, ABOi/TPE ≥6 was an independent risk factor for RFS (aHR 1.99, 95% CI:1.02-3.86, P = 0.042) and HCC recurrence (aHR 2.42, 95% CI:1.05-5.57, P = 0.037). More than six pretransplant TPE sessions may increase the risk of HCC recurrence after ABOi LDLT. Reducing TPE sessions to fewer than six should be considered while maintaining immunological stability through IA titer control.

The Donation-after-Circulatory-Death (DCD) heart transplantation program increases donor pool but resulting in more serious ischemic-related myocardial injury (IRI), leading to higher incidence of primary graft dysfunction (PGD). Ex-vivo machine perfusion (EVMP) for DCD heart is being considered a useful aid in improving grafts number and quality assessment, aiming to better outcomes. In this review we will analyze the role of EVMP techniques in the context of DCD with special attention to their clinical aims and results and future perspectives. A review of available clinical and pre-clinical studies involving EVMP with DCD donation model was performed. Thirty-four original articles about preclinical studies were found. First studies were designed to evaluate graft function in DCD hearts after EVMP, while recent research focus on possible therapies that could be associated with EVMP. Twenty-one original articles about clinical studies were found with the Organ-Care-System (TransMedics) as MP used. Outcomes, such as survival rates or rejection episodes, are comparable to outcomes from donation-after-brain-death. EVMP in the setting of DCD heart transplantation can be a valid tool for organ preservation and transport. The role of pre-clinical research will be crucial to reduce IRI, achieve organ reconditioning and reduce incidence of PGD.

The annual meeting of the French GTI (Transplantation and Infection Group) focused on donor-derived infections (DDIs) in solid organ transplant (SOT) recipients. Given the ongoing organ shortage, rigorous donor screening is essential to detect potential infectious risks. Donor evaluation should include medical history, travel, vaccination status, serologies, and exposures. Various pathogens are of concern, including viruses (HIV, hepatitis, BK polyomavirus), multidrug-resistant bacteria, fungi, and emerging arboviruses like West Nile virus and dengue. HIV-positive donor to HIV-positive recipient (D+/R+) transplantations are increasingly accepted, with promising outcomes. Hepatitis E (HEV) is now the most common viral hepatitis and may lead to chronic infection in SOT recipients, requiring ribavirin treatment. Non-Candida fungal infections, though rare, are associated with high mortality and demand early recognition. Climate change and globalization are expanding the range of vector-borne infections, necessitating seasonal and regional screening. BK polyomavirus remains a major complication in kidney transplant recipients, and monitoring viral load is critical. Bacterial infections from donors are uncommon but should be evaluated based on site, organism, resistance profile, and treatment history. Overall, maintaining safety in transplantation requires constant vigilance, updated knowledge, and personalized risk-benefit analysis to adapt to emerging infectious threats-especially amid ongoing organ scarcity.

Antibody-mediated rejection (ABMR) is the leading cause of long-term graft loss in pediatric kidney transplantation (KTx). While donor-specific HLA antibodies are established contributors, emerging evidence suggests a role for non-HLA antibodies in ABMR pathogenesis. In this descriptive study, we analyzed 60 non-HLA antibodies in 77 pediatric KTx recipients using serum samples collected pre-transplant, post-transplant, and at ABMR diagnosis. During a median follow-up of 4.83 years, 29.8% developed ABMR, with a median onset of 3.67 years. Non-HLA antibody presence prior to KTx was not influenced by pre-transplant dialysis; over half of the patients already had >15 positive non-HLA antibodies. The cumulative antibody profile remained stable 1-2 years post-KTx, with no association between late ABMR and antibody strength or breadth. However, ACTIN (higher risk) and CGB5 (lower risk) at 1-2 years post-KTx, as well as SNRPB2 pre-transplant, were significantly associated with ABMR (p < 0.05). IL-21 levels increased in controls over time (p < 0.05), although driven by five patients with notably high levels. Our findings support a potential involvement of non-HLA antibodies in pediatric ABMR. Nevertheless, larger studies are needed to validate the predictive value of individual non-HLA antibodies for clinical application.