Transplantology, Volume 6, Issue 3 (September 2025) – 6 articles

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article

Background: Graft-versus-host disease (GVHD) is a rare but serious complication following solid organ transplantation (SOT), particularly in transplants involving organs with a high volume of passenger donor T-lymphocytes. This case highlights the clinical course and diagnostic challenges of GVHD following simultaneous pancreas and pre-emptive kidney transplantation. Methods: A 51-year-old male with long-standing type 1 diabetes mellitus underwent simultaneous pancreas and kidney transplantation with induction therapy using rabbit anti-thymocyte globulin and methylprednisolone. Three months post-transplant, he presented with a diffuse lichenoid cutaneous eruption. Diagnostic evaluation included an extensive infectious workup, skin punch biopsy, liver and bone marrow biopsies, and microchimerism assay. Results: Skin biopsy revealed interface vacuolar dermatitis consistent with cutaneous GVHD. Subsequent liver and bone marrow biopsies confirmed GVHD involvement, with microchimerism assay showing 43% donor-origin T-cells in the bone marrow. Initial treatment with systemic and topical corticosteroids led to temporary improvement. However, the patient developed bone marrow suppression, recurrent bacteremia, and invasive fungal infection, resulting in a prolonged ICU stay and ultimately death. Conclusions: This case underscores the importance of considering SOT-GVHD in patients receiving organs rich in donor lymphocytes, such as pancreas transplants. Early recognition and multidisciplinary management are critical to improving outcomes in this rare but life-threatening condition. Full article

Artificial Intelligence (AI) and machine learning (ML) are increasingly being applied across the transplantation care pathway, supporting tasks such as donor–recipient matching, immunological risk stratification, early detection of graft dysfunction, and optimisation of immunosuppressive therapy. This review provides a structured synthesis of current AI applications in transplantation, with a focus on underrepresented areas including real-time graft viability assessment, adaptive immunosuppression, and cross-organ immune modelling. The review also examines the translational infrastructure needed for clinical implementation, such as federated learning, explainable AI (XAI), and data governance. Evidence suggests that AI-based models can improve predictive accuracy and clinical decision support when compared to conventional approaches. However, limitations related to data quality, algorithmic bias, model transparency, and integration into clinical workflows remain. Addressing these challenges through rigorous validation, ethical oversight, and interdisciplinary collaboration will be necessary to support the safe and effective use of AI in transplant medicine. Full article

Background/Objectives: Heart transplantation is a life-saving procedure for patients with end-stage heart failure, yet it involves significant psychological and emotional challenges throughout its various stages. International guidelines recommend a multi-professional approach to the care of these patients and a psycho-social assessment for listing. The recommendations focus on content aspects, but not on the psychometric measure to be administered to patients as part of the assessment. Therefore, the purpose of this study is to provide the preliminary results of administering the protocol used by our center, measuring coping strategies, cognitive functioning, quality of life, and psychological distress in a sample of patients who are candidates for and undergo cardiac transplantation, and to observe any variations after the procedure. Methods: We conducted a comprehensive psychological-clinical assessment involving 40 patients, focusing on psychosocial functioning, cognitive reserves, mental health, and coping strategies. Tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Beck Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), General Anxiety Disorder 7 (GAD-7), and Medical Outcomes Survey Short Form 36 (SF-36) were employed to evaluate readiness for transplantation and post-transplant adaptation. Results: Results showed high levels of clinical anxiety (52.5%) and low perceived physical health (98%) before the transplant, while post-operative evaluations indicated reduced anxiety (13.51%) and depressive symptoms (10.81%), along with improved psychological well-being and reintegration into daily life. Conclusions: These results show improvement in physical and cognitive levels, accompanied by a state of enhanced psychological well-being after transplantation. A longitudinal psychological approach, from pre-transplant screening to post-discharge follow-up, is needed to address distress, improve coping mechanisms, and promote treatment adherence. This integrative strategy is critical to improving the quality of life and long-term outcomes for heart transplant recipients. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Background: Ischemia–reperfusion injury (IRI) is a key contributor to graft dysfunction in kidney transplantation. Cell-free mitochondrial DNA (mtDNA) is increasingly recognized as a damage-associated molecular pattern (DAMP) and biomarker in IRI, but its prognostic role in living donor kidney transplantation (LDKT) remains unclear. Methods: This post hoc analysis of the VAPOR-1 study evaluated urinary mtDNA (UmtDNA) in 57 LDKT recipients. MtDNA levels (ND1, ND6, and D-loop) were measured at five early timepoints post-transplantation using qPCR. Associations between early UmtDNA and long-term graft function, defined by estimated glomerular filtration rate (eGFR) at 1, 12, and 24 months, were analyzed. Results: Higher UmtDNA levels in the first urine after reperfusion were significantly associated with improved eGFR at 12 months and a positive change in eGFR between month 1 and 24. These associations were not attributable to urine creatinine levels or mitochondrial copy number. Conclusions: In this LDKT cohort, elevated early UmtDNA may reflect a well-functioning graft capable of clearing systemic mtDNA rather than ongoing tubular injury. These findings suggest that the biological interpretation of mtDNA as a biomarker is context-dependent and call for careful reconsideration of its role in early transplant monitoring. Full article