Outcomes after liver transplantation have continuously improved over the past decades, but long-term survival rates are still lower than in the general population. The liver has distinct immunological functions linked to its unique anatomical configuration and to its harbouring of a large number of cells with fundamental immunological roles. The transplanted liver can modulate the immunological system of the recipient to promote tolerance, thus offering the potential for less aggressive immunosuppression. The selection and adjustment of immunosuppressive drugs should be individualised to optimally control alloreactivity while mitigating toxicities. Routine laboratory tests are not accurate enough to make a confident diagnosis of allograft rejection. Although several promising biomarkers are being investigated, none of them is sufficiently validated for routine use; hence, liver biopsy remains necessary to guide clinical decisions. Recently, there has been an exponential increase in the use of immune checkpoint inhibitors due to the unquestionable oncological benefits they provide for many patients with advanced-stage tumours. It is expected that their use will also increase in liver transplant recipients and that this might affect the incidence of allograft rejection. Currently, the evidence regarding the efficacy and safety of immune checkpoint inhibitors in liver transplant recipients is limited and cases of severe allograft rejection have been reported. In this review, we discuss the clinical relevance of alloimmune disease, the role of minimisation/withdrawal of immunosuppression, and provide practical guidance for using checkpoint inhibitors in liver transplant recipients.

Objective Organ transplant recipients receive immunosuppressive regimens to prevent transplant rejection, which put them at increased risk for opportunistic infections like cytomegalovirus (CMV). Ganciclovir and Valganciclovir are mostly used to prevent or treat CMV. Any incorrect use of the drug may have serious consequences for patients. In this study, the outcome of transplant recipients was assessed in relation to the optimal or suboptimal use of Ganciclovir or Valganciclovir. Methods This study was performed on 148 hospitalized patients who received Ganciclovir or Valganciclovir in the nephrology and kidney transplantation departments of our university hospitals, from March 2012 to December 2016. Patients' demographic and clinical data including dose and duration of treatment were collected and then analyzed in comparison with the standard CMV treatment protocols. Findings About 94.6% of patients received Ganciclovir or Valganciclovir therapy consistent with the standard defined indications. The mean ratio of prescribed daily dose to the optimal dose was 2.9 in the first dose, 2.0 in the second dose, 1.3 in the third dose, and 1.5 in the fourth dose. From 148 included patients, 26.5% experienced CMV infection once, 7.2% experienced CMV infection twice, and 1.2% had CMV infection for 3 times, within six-month follow-up after first episode of antiviral therapy during hospitalization. Conclusion In this study, empiric anti-CMV therapy was initially given. The doses used were generally higher than recommended but we could not find more adverse events in the patients receiving high initial doses. In any case, it seems necessary to advocate use of standard treatment guidelines to avoid adverse outcomes.

<h4>Objective</h4>To comparatively evaluate the efficacy and safety of induction therapies in solid organ transplantation (SOT) using a Bayesian network meta-analysis (NMA).<h4>Methods</h4>Randomized controlled trials (RCTs) assessing induction therapies were systematically identified across major databases (up to November 20, 2024). The screening, data extraction, and risk of bias (ROB) assessment were independently conducted by two reviewers through standardized tools. Bayesian NMA synthesized outcomes, including rejection, graft/overall survival, and infection rates.<h4>Results</h4>Sixty-eight RCTs (9,626 patients) evaluating 12 therapies were included. Surface Under the Cumulative Ranking Area (SUCRA) probabilities identified alemtuzumab as the most effective agent for reducing rejection rates (93.9%), followed by antilymphocyte globulin (ALG, 87.0%) and belimumab (77.0%). For graft survival, OKT3 ranked highest (87.9%), with subsequent superiority for ALG (83.5%) and alemtuzumab (75.6%). Basiliximab demonstrated the highest overall survival benefit (88.0%), outperforming rabbit antithymocyte globulin (rATG, 82.1%) and inolimomab (70.3%). Belimumab showed the greatest infection risk reduction (94.4%), surpassing alemtuzumab (80.0%) and basiliximab (74.5%).<h4>Conclusion</h4>Alemtuzumab emerged as the optimal therapy for minimizing rejection, while OKT3 and basiliximab were superior for graft and overall survival, respectively. Belimumab exhibited the strongest potential for reducing incidence of infection. These findings highlight therapy-specific advantages for optimizing SOT outcomes.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42025634120.

<h4>Background</h4>Although postoperative rejection in transplant patients can be managed with immunosuppressants, their use is associated with some complications due to excessive immunosuppression. Recent animal studies in allotransplantation have suggested that certain ingredients of Chinese herbal medicine can extend transplant survival. However, their effects on transplantation have not been systematically reviewed and analyzed. The aim of this study was to evaluate the effects of herbal medicine ingredients on complications and survival of transplanted organs after heart, liver and kidney transplantation, and to explore the possible mechanism of action.<h4>Materials and methods</h4>Databases, including PubMed, EMBASE, Cochrane Library, Web of Science, Wang Fang, China National Knowledge Infrastructure (CNKI), China Science and Technological Journal Database (VIP) and Chinese Biomedical Literature Database (CBM), were searched up to January 1 2025. Animal studies reporting the effects of Chinese herbal medicine ingredients (HMIs) on postoperative complications and organ transplant survival/outcome were included. Methodological quality was assessed using the SYRCLE risk of bias tool. Meta-analysis was performed using R 4.3 software to assess levels of inflammatory factors, oxidative stress markers, apoptosis markers, indicators of liver/kidney function, median graft survival time and immune cell subsets.<h4>Results and conclusions</h4>A total of 18 studies, involving 357 rodents were included. The overall quality of the included reports was moderate. We found that HMIs enhanced organ graft survival by reducing the Banff score, extending the median survival time (MST), and exerting anti-inflammatory, antioxidant and anti-apoptotic effects. HMIs can also inhibit T cell proliferation, dendritic cell (DC) maturation and increase the proportion of CD4⁺ regulatory T (Treg) cells. Furthermore, the improvement in liver and kidney function indicators, such as alanine aminotransferase (ALT), aspartate transaminase (AST), Serum creatinine (Scr) and blood urea nitrogen (BUN) also suggested protective effects of HMIs on liver and kidney function. However, the high heterogeneity observed in several analyses highlights the need for standardized experimental designs and further studies to confirm these findings and to explore their underlying mechanisms. Thus, our meta-analysis indicates that HMIs improve transplantation outcomes in animal models. These results lay a solid foundation for translating HMIs into clinical strategies for improving transplantation outcomes.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/view/CRD420251002755, identifier crd420251002755.

The goal of achieving clinical operational tolerance in liver transplantation has sparked significant interest, driven by the desire to mitigate the long-term adverse effects of immunosuppression. Advances in understanding the immunological mechanisms underpinning operational tolerance in liver transplantation have highlighted the central role of regulatory T cells and tolerogenic dendritic cells. These cells actively suppress effector immune responses and aid in achieving operational tolerance. Immunosuppressive medication differentially influences the expansion, survival, and function of these cells, demonstrating the importance of understanding the potential of immunosuppressive regimens to optimize the possibility of achieving an immunosuppression-free state. The potential of stepwise immunosuppressive reduction to achieve operational tolerance without compromising graft function has been demonstrated. The immunosuppressive withdrawal protocols underline the feasibility and safety of immunosuppressive withdrawal in selected liver transplant recipients, highlighting factors such as time since transplantation, recipient age, and gender as strong predictors of success. Furthermore, minimization of immunosuppressive, even early post transplantation, has been shown to be successful and sets the stage for successful immunosuppression withdrawal later. This review highlights the necessity to optimize immunosuppressive regimens by demonstrating its possibility to aid in achieving minimal immunosuppressive to maximize success rates of drug withdrawal and diminish the cumulative immunosuppressive related complications to increase the quality of life of liver transplant recipients.

Organ transplantation represents a definitive therapeutic modality for end-stage organ failure, yet it is plagued by formidable challenges encompassing allogeneic immune rejection and the inherent limitations of conventional immunosuppressive regimens. Nonspecific immunosuppression not only precipitates severe adverse events such as opportunistic infections and malignancies but also fails to precisely modulate the local immune microenvironment. The core innovation of this review lies in the systematic integration of the distinctive advantages of nanotechnology-including targeted delivery, multifunctional synergy, and stimuli-responsive intelligence-with transplant immune regulation, encompassing a comprehensive analysis spanning mechanistic elucidation, strategic optimization, and clinical translation. We first delineate the pivotal mechanisms underlying immune rejection, including the regulatory roles of the transplant immune microenvironment, T lymphocytes, macrophages, and oxidative stress in ischemia-reperfusion injury (IRI). Subsequently, we conduct a critical comparison between conventional immunosuppressants and emerging therapeutic strategies, with a particular focus on how nanoplatforms enable spatiotemporally precise immune modulation. This includes targeting the transplant immune microenvironment, reprogramming T cell/macrophage functions, mitigating oxidative stress, facilitating tissue repair and regeneration, as well as inducing immune tolerance via both active and passive approaches. Additionally, we discuss innovative nanotechnological strategies such as the optimization of organ cryopreservation protocols. In summary, nanotechnology offers a targeted, multifunctional, and long-acting paradigm for transplant immune regulation, albeit confronted with formidable translational bottlenecks. Future integration with interdisciplinary technologies will undoubtedly propel the field toward the goal of precision immune modulation in organ transplantation.

Cancer morbidity and mortality are increasingly apparent risks in transplant recipients, thus reducing life quality and overall survival. These risks have largely been attributed to long-term immunosuppressive drug therapy, which remains necessary to prevent organ allograft rejection. Interestingly, however, recent studies challenge the premise that all immunosuppressive drugs necessarily promote cancer. A particular class of immunosuppressants, referred to as mammalian target of rapamycin (mTOR) inhibitors, has been shown to have potent anti-cancer effects that are presently being tested in clinical studies. The focus of this review is to present current evidence that allows us to understand better the dual immunosuppressive and anti-cancer functions of this class of drugs used to prevent allograft rejection. We will concentrate on the different functions of mTOR that allow it to simultaneously control the immune system and tumor development. We will also discuss results from current clinical studies that either support or refute this potential dualistic role.

Immunosuppressive drugs have facilitated the progression of solid organ transplantation from experimental therapy to routine practice, however transplant recipients are still susceptible to chronic rejection and co-morbidities. The emergence of regulatory T cells (Treg) as a key regulator of the immune system, together with an abundance of evidence from experimental transplant models, has led to clinical trials asking whether Treg can improve transplant outcomes. However, given that Treg cellular therapy will only be acceptable if introduced into current immunosuppressive regimens, a critical question is how Treg will respond in the presence of concomitant immunosuppression. Whilst in vitro data are available, very few credible experiments have been done asking whether individual immunosuppressive drugs have a positive, a neutral or a detrimental impact on the Treg function in vivo . Thus the aims of this thesis were firstly to generate sufficient numbers of adaptive Treg for extensive experimental use and secondly to evaluate their ability to control transplant rejection in vivo in the presence of biologically valid doses of individual, clinically relevant immunosuppressive drugs. Importantly, the model chosen was the heterotopic heart transplant model in lymphoreplete mice to avoid possible artefacts that can occur in cell reconstituted lympho-depleted mice. The model also has the added advantage that by dealing with an intact immune system, it perhaps represents a small st

EBV-infected B-cell lymphomas are a potentially life-threatening complication in bone marrow and solid organ transplant recipients. Immunosuppressive drugs required to prevent allograft rejection also impair anti-EBV T-cell immunity, thereby increasing the risk of EBV-associated disease. Here we demonstrate that the immunosuppressant rapamycin (RAPA) has a strong antiproliferative effect in vitro on B-cell lines derived from organ transplant recipients with EBV-associated posttransplant lymphoproliferative disorder (PTLD). Furthermore, RAPA significantly inhibits or delays the growth of solid tumors established from EBV-infected B-cell lines in a xenogeneic mouse model of PTLD. RAPA acts via cell cycle arrest, induction of apoptosis, and, most importantly, inhibition of interleukin 10 secretion, a necessary autocrine growth factor. The reduced interleukin 10 production is accompanied by corresponding decreases in the constitutive activation of the growth-promoting transcription factors signal transducer and activator of transcription 1 and 3. Thus, RAPA can limit B-cell lymphoma growth while simultaneously providing immunosuppression to prevent graft rejection in patients who are otherwise at risk for EBV-associated PTLD. Moreover, these findings may have application to other EBV-associated malignancies.

<h4>Background</h4>Vascularized composite allotransplantation (VCA) offers unique reconstructive solutions for severe tissue loss, restoring form and function. Acute and chronic rejection remains a significant barrier, with acute episodes occurring in most recipients and chronic rejection persisting as the leading cause of graft failure. Unlike solid organ transplantation, VCA involves highly immunogenic tissues, like skin and mucosa, making rejection more frequent and challenging to manage.<h4>Methods</h4>A systematic review was conducted following PRISMA 2020, searching PubMed/MEDLINE, EMBASE, and Web of Science for original human VCA studies reporting immunosuppressive protocols and outcomes in acute or chronic rejection. Quality was assessed using the Newcastle-Ottawa Scale and Level of Evidence; extracted data included demographics, regimens, rejection episodes, treatments, and graft survival.<h4>Results</h4>Fourty-six studies (136 recipients) met inclusion criteria: upper extremity (n=69; 51%), face (n=33; 24%), abdominal wall (n=33; 24%), scalp and penile (each n=1; 0.7%). Acute rejection occurred in 81/136 (60%) within year 1, most often at POW 1-2 (n=52), 5-12 (n=42), and 13-52 (n=30). Severity was Banff grade I (n=49; 36%), II (n=73; 54%), III (n=50; 37%), and severe IV (n=1; 0.7%). Common symptoms included skin lesions (n=43; 32%), edema (n=32; 24%), erythema (n=29; 21%), and rash (n=15; 11%), with some experiencing numbness (n=4; 2.9%), tingling (n=5; 3.7%), or burning sensations (n=5; 3.7%). Corticosteroids were the mainstay (n=98; 72%)-methylprednisolone (n=31; 23%), clobetasol (n=15; 11%), and prednisone (n=11; 8.1%); tacrolimus was used in 49 (36%), including topical in 29 (21%). Other immunosuppressants included antithymocyte globulin (n=19; 14%), alemtuzumab (n=11; 8.1%), mycophenolate mofetil (n=11; 8.1%), and rituximab (n=6; 4.4%); basiliximab (n=4; 2.9%), sirolimus (n=2; 1.5%), and plasmapheresis (n=4; 2.9%) were used selectively. Monotherapy was used in 42 episodes, and dual therapy in 51, most commonly methylprednisolone plus topical tacrolimus (n=26).<h4>Conclusion</h4>This review underscores the ongoing challenge of rejection in VCA and the need for improved treatment strategies, with corticosteroids, calcineurin inhibitors, and mycophenolate mofetil remaining standard while emerging biologicals offer promise. Acute rejection is often manageable yet threatens graft survival, whereas chronic rejection is less reported, likely under-recognized and harder to treat, underscoring need for novel immunomodulators, standardized protocols, and prevention to improve outcomes.

Solid organ transplantation (SOT) is a critical treatment for end-stage organ failure. Still, lifelong immunosuppression leaves recipients vulnerable to opportunistic viral infections, which can lead to severe complications such as graft dysfunction and post-transplant lymphoproliferative disorder. With emerging viral threats such as SARS-CoV-2 and arboviruses, alongside persistent challenges posed by CMV, EBV, and BKV, this review is timely in addressing the evolving landscape of post-transplant viral infections and their management. Recent studies highlight how immunosuppression impairs both innate and adaptive antiviral defenses, including diminished toll-like receptor signaling, dysfunction of NK cells, and disrupted T- and B-cell responses. Viruses exploit these deficits through immune evasion strategies, such as MHC-I downregulation and the production of immunosuppressive microRNA. Advances in management include antiviral prophylaxis, adoptive T-cell therapy, and immune monitoring, with emerging therapies like virus-specific T-cell infusions and complement inhibition showing promise. The findings underscore the need for personalized, organ-specific approaches to post-transplant care. Enhanced surveillance, vaccination strategies, and novel immunotherapies are critical in mitigating viral risks. Future research should focus on immune-risk stratification and the development of an adaptable therapeutic approach to enhance transplant outcomes in the face of evolving viral threats.

<h4>Aim</h4>To summarize the evidence on the association of oral candidiasis with solid organ transplantation in case-control and cohort studies.<h4>Methods</h4>The quality of studies was assessed using the Newcastle-Ottawa scale. Random-effects restricted maximum likelihood model or Fixed-effects Mantel-Haenszel models were used to pool the results appropriately, and sensitivity analysis, subgroup analysis, and publication bias were assessed. The certainty of evidence was assessed using the GRADE approach.<h4>Results</h4>The pooled OR of candidiasis in immunosuppressed individuals receiving solid organ transplants compared to controls was found to be 3.52 (95% CI: 1.92, 6.46; p < 0.05). The pooled OR of oral candidiasis in kidney transplant recipients compared to controls was 3.53 (95% CI: 1.92, 6.49; p < 0.05); for liver, 20.12 (95% CI: 3.83, 105.74; p < 0 .05), and heart, 152.01 (95% CI: 17.71, 1304.96; p < 0.05).<h4>Conclusions</h4>There was moderate certainty of evidence that there was an increased risk of oral candidiasis in immunosuppressed patients who received solid organ transplants compared to healthy controls. Similarly, the evidence was moderate for subgroup analysis regarding the kidney transplant recipients, liver transplant recipients, and heart transplant recipients. Due to the lack of current research, future research should evaluate the risk of oral candidiasis in patients receiving pancreas or small bowel transplants. Also, future studies should evaluate the role of prophylactic antifungals in immunosuppressed solid organ transplant recipients.<h4>Trial registration</h4>PROSPERO number: CRD42022363816.

international transplant tourism and a venue for testing pharmaceutical anti-rejection drugs. According to Kilgour and Matas in 2007, organ transplant recipients Allegations of forced organ harvesting from Falun Gong practitioners and other prisoners in the People's Republic of China have raised concern within the international community. Initial reports of organ harvesting began with the Falun Gong-affiliated Epoch Times in 2006. In a subsequent report, known as the Kilgour–Matas report, former lawmaker David Kilgour and legal counsel David Matas estimate China has one of the largest organ transplant programs in the world. China Daily, controlled by the Chinese Communist Party, reported that as many as 20,000 organ transplants were performed in 2006. According to the Chinese Ministry of Health, kidney transplants increased from 3,000 to 6,000 per year from 1997 to 2000, peaking at around 10,000 in 2004 before falling again. Some sources say the actual number of transplants is significantly higher based on hospital records. Wait times for obtaining vital organs in China are among the shortest in the world—often just weeks for organs such as kidneys, livers, and hearts. This has made it a destination for international transplant…

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