Transplant International最新文献

Mixed hepatocellular carcinoma (HCC) with cholangiocarcinoma (HCC-CCA) is an aggressive primary liver cancer and difficult to distinguish from HCC using non-invasive methods. Outcomes of patients incidentally diagnosed with HCC-CCA after LT relative to pure HCC with similar tumor burden were investigated. Medical records of patients undergoing LT (n = 1,898) for HCC (n = 493) from 6/2008-9/2023 were reviewed. Patients incidentally diagnosed with HCC-CCA were propensity matched to HCC patients undergoing LT. Independent analyses were performed using pre-LT (Match1; identifiable pre-LT) and explant pathology (Match2, more prognostic) characteristics. Incidental HCC-CCA occurred in 19 (3.9%) patients; all assumed to have HCC pre-LT and received HCC-directed neoadjuvant treatment. When matched on pre-LT characteristics (Match1, n = 57), more patients with HCC-CCA were outside Milan or University of California, San Francisco criteria on explant (p = 0.01). More patients with HCC-CCA underwent neoadjuvant microwave ablation (p = 0.02) compared to HCC Match2 (n = 45) but were otherwise similar demographically and clinically. Overall and recurrence-free survival were lower for HCC-CCA in Match1 (p = 0.003 and p < 0.001, respectively) and Match2 (p < 0.001 and p = 0.001, respectively). HCC-CCA has an aggressive phenotype with high recurrence after LT. Better screening tools and biomarkers are needed to distinguish HCC-CCA from HCC to ensure patients receive appropriate treatment and maximize post-LT outcomes.

Liver transplantation (LT) is the definitive treatment for selected acute and chronic liver diseases, yet standard national listing criteria do not encompass all clinical situations. To address this, the United Kingdom (UK) established the National Appeals Panel (NAP) in 2011 to review exceptional cases, aiming to ensure equitable access while safeguarding allocation of scarce donor organs. We conducted a retrospective analysis of all appeals submitted to the NAP between 2011 and 2020. 149 appeals were received: 139 (93.3%) adults and 10 (6.7%) paediatric patients. Overall, 128 (85.9%) appeals were approved, 19 (12.8%) declined, and 2 (1.3%) withdrawn. Approval was more frequent for adult super-urgent than elective requests (92.9% vs. 79.5%). Of 118 approved adults, 95 (80.5%) underwent LT, while 23 (19.5%) did not, most often due to deterioration on the waiting list. Transplanted adults included 46.3% super-urgent cases, with 20% ventilated and 25.3% on renal replacement therapy, yet achieved excellent outcomes with 98% one-year and 90% five-year survival. All 10 paediatric appeals were approved, with one child dying on the list and nine transplanted. Declined appeals mainly involved older patients with malignant indications. This review highlights the NAP's role in expanding LT access while ensuring equity and governance.

This study evaluates changes in cellular immunity components, from chronic kidney disease stage V (CKD-V) to long-term transplantation (lKTx). We applied flow cytometry to determine total, CD4⁺, CD8⁺, CD28^- T-lymphocytes, Natural killer cells (NK) and regulatory T-lymphocytes (Tregs), in peripheral blood of 56 patients with CKD-V, 207 patients on hemodialysis (HD), 149 recently transplanted (rKTx), 26 lKTx patients and 49 healthy volunteers as a control group (CG). Lymphocyte proportion decreased in CKD vs. CG [20.2 (14.4-25.8) vs. 29.7 (24.4-38.1)%, p < 0.001] without further deterioration in HD [19.9 (15.3-23.7)%, p = 0.83 vs. CKD-V] and increased in rKTx [24.7 (20-32.6)%, p < 0.001 vs. HD], and lKTx [25.5 (21.9-35)%, p = 0.16 vs. CG]. Similar kinetics were observed in CD4⁺ subpopulations, however CD8⁺ T-cells gradually increased from CG to lKTx. NK remained stable in CKD-V and HD, reduced in rKTx, and marginally increased in lKTx. Tregs gradually declined until HD and suboptimally improved with transplantation. CD28^- subpopulations largely increased in lKTx, compared with HD [CD4⁺CD28^-: 12.6 (4.7-27.6) vs. 6 (2.1-13.2)%, p = 0.006, CD8⁺CD28^-: 68.4 (54.4-90.3) vs. 45.5 (28.4-58.9)%, p < 0.001], independently of age for CD8⁺CD28^- (p = 0.33). Cellular immunity subpopulations show significant changes in the spectrum of CKD, with transplantation restoring total lymphocytes and CD4⁺ T-cells, but not Tregs and NK. LKTx was associated with a large increase in CD28^- subpopulations.

Donor-derived cell free DNA (dd-cfDNA) is an established biomarker for detection of rejection in single organ transplants; data is limited in multi-organ transplant (MOT) recipients. "Use of dd-cfDNA in Multi-Organ Transplant Recipients" (MOTR) was a multicenter, prospective, cross-sectional study that assessed dd-cfDNA fraction (%) and donor quantity score (DQS, cp/mL) in pancreas-kidney (PKT), heart-kidney (HKT), and liver-kidney (LKT) recipients. We explored dd-cfDNA baseline levels across the different organ combinations, and compared them to kidney-only (KT) and heart-only (HT) transplant recipients. Among 347 MOT recipients from 18 sites (PKT = 183, HKT = 57, LKT = 107), most (88.2%) had simultaneous transplants. Median dd-cfDNA levels in PKT and HKT recipients were not significantly different from KT; median dd-cfDNA levels among HKT recipients were significantly higher than in HT recipients (p < 0.001). In LKT recipients, median dd-cfDNA was significantly higher compared to KT (p < 0.001). dd-cfDNA showed associations with organ impairment indicated by abnormal values of pancreatic and liver enzymes in PKT and LKT. As the largest multi-center study to date evaluating dd-cfDNA levels in MOT recipients, MOTR showed that organ-specific physiology affects dd-cfDNA levels across organ transplant combinations, laying the foundation for future efforts to use dd-cfDNA to assess organ-specific signatures of allograft injury in MOT recipients.

The use of extended criteria donors (ECD) has become increasingly important in lung transplantation to address organ donor shortages. To better assess lung graft quality and optimize donor selection, several scores have been developed. This study assesses whether Swiss lung acceptance practice is associated with three validated lung donor scores - the Oto Score, Eurotransplant Score (ET), and Zurich Donor Score (ZDS) - in both DBD and DCD donors. Due to limited clinical data, certain parameters of the Oto and ET Scores were adapted (aOto and aET). Data from 1515 actual deceased donors between 01.07.2014 and 30.06.2024 were analyzed. Logistic regression and AUC-ROC analysis were used to evaluate the scores' discriminative ability. Results showed that all three scores were associated with lung acceptance, with AUC values indicating acceptable to moderate discriminative ability - 0.75 for aOto, 0.70 for aET, and 0.77 for ZDS - and DCD donors being consistently less likely to be accepted for lung transplantation compared to DBD donors. Nonetheless, all three scores showed limitations as standalone models. Developing a novel, nationally applicable Swiss prediction tool integrating current lung acceptance criteria and recipient factors could improve donor-recipient matching, support more efficient organ utilization, and potentially increase transplant activity.

Determination of unacceptable human leukocyte antigen (HLA) mismatches (UAM) before kidney transplantation (KT) aims at minimizing immunological risk and routinely involves Luminex single antigen bead (SAB) testing. SAB-UAM criteria, however, often lack standardization. We implemented standardized mean fluorescence intensity (MFI)-based SAB-UAM criteria in four German transplant centers and prospectively studied the consequences on waitlist composition as well as waiting time, early antibody-mediated rejection (AMR) and graft loss in 267 patients. HLA were deemed unacceptable in case of CDC-reactivity or antibodies against known HLA from previous transplants irrespective of MFI. For all other antibodies, the MFI cut-off was 5.000 with the exception of 10.000 for anti-HLA DQ. We observed significant accumulation of highly sensitized patients (virtual panel-reactivity >95%) on the waiting list during the study period. Median time to KT was longer in patients with UAM, but differences were not statistically significant. Patients with preformed donor-specific anti-HLA antibodies (DSA) below the UAM cut-off criteria (39/267) experienced more AMR episodes compared to DSA-negative patients (10.3% vs. 1.3%, p < 0.001). Graft survival, however, was not statistically different over a median follow-up of four years. Standardized SAB-UAM criteria associated with good short-term outcomes but resulted in accumulation of highly sensitized patients on the waiting list.

Perioperative complications are common in kidney transplantation. Enhanced recovery after surgery (ERAS) is a well-established multimodal perioperative care pathway designed to improve patient outcomes, however, its efficacy in renal transplant remains poorly described. Participating centres included adult renal transplant recipients and 30-day follow-up data. The primary outcome was LOS. Multivariable hierarchical models compared cohorts. 213 patients were included in the study period. 18/23 UK kidney transplant centres were represented. Analysis of the perioperative care delivery demonstrated similar patterns irrespective of reported protocols, with a tendency towards ERAS-type care. Between cohorts, the incidence of complications were similar; formal ERAS 14.3%, ERAS informal 17.0%, no ERAS 12.6%; p = 0.64. Median LOS was also similar; formal ERAS 6.0 days (5.0-11.5), informal ERAS 7.0 days (5.0-10.5) vs. no ERAS 6.0 days (5.0-10.5); p = 0.75. Readmissions were comparable; p = 0.721. Multivariable models confirmed these findings and demonstrated frailer patients had longer LOS and more readmissions. Currently, most UK renal transplant centres deliver a form of peri-operative ERAS care, indicating broad adoption of ERAS principles. Consequently, a formal ERAS protocol is not associated with decreased complications, LOS or readmissions. Efforts to improve outcomes should focus on prehabilitation of at-risk groups on the waiting list.