Current Opinion in Organ Transplantation最新文献

Purpose of review: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery.

Recent findings: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels.

Summary: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

Purpose of review: The increasing success of liver transplantation in hepatocellular carcinoma (HCC) drives an ever-evolving search for innovative strategies to broaden eligible patients' pools. Recent advances in immuno-oncology have turned the spotlight on immune checkpoint inhibitors (ICIs). This review offers an updated overview of ICIs in liver transplantation for HCC, exploring neoadjuvant and adjuvant approaches and addressing unanswered questions on safety, patients' selection, and response predictors.

Recent findings: ICIs have transitioned from being a last-chance therapeutic hope to becoming an integral cornerstone in the treatment of advanced HCC, holding great promise as a compelling option not only to downstage patients for transplantation but also as an alternative strategy in addressing posttransplantation disease recurrence. Despite ongoing refinements in immunotherapeutic agents, the complex molecular pathways involved emphasize the need for a comprehensive approach to integrate immunotherapy in liver transplantation.

Summary: Initial concerns about graft rejection, with ICIs as a bridging therapy to liver transplantation, were successfully addressed using adequate immunosuppressants strategies and minimized with a sufficient washout period. Post-liver transplantation disease recurrence remains challenging, requiring a balance between effective therapy and preserving graft function. Emphasis should be placed on clinical trials validating the risk-benefit ratio of ICIs for liver transplantation, guiding appropriate patients' selection, and establishing clear management pathways.

Purpose of review: Using transplant oncology principles, selected patients with intrahepatic cholangiocarcinoma (iCCA) may achieve long-term survival after liver transplantation. Strategies for identifying and managing these patients are discussed in this review.

Recent findings: Unlike initial reports, several modern series have reported positive outcomes after liver transplantation for iCCA. The main challenges are in identifying the appropriate candidates and graft scarcity. Tumor burden and response to neoadjuvant therapies have been successfully used to identify favorable biology in unresectable cases. New molecular biomarkers will probably predict this response in the future. Also, new technologies and better strategies have been used to increase graft availability for these patients without affecting the liver waitlist.

Summary: Liver transplantation for the management of patients with unresectable iCCA is currently a reality under strict research protocols. Who is a candidate for transplantation, when to use neoadjuvant and locoregional therapies, and how to increase graft availability are the main topics of this review.

Purpose of review: Regulatory dendritic cells (DCregs; also 'tolerogenic DCs'), innate immune cells that regulate the alloimmune response, are a novel cellular therapy for organ transplantation. Preliminary results from early-phase clinical trials in live donor kidney and liver transplantation are promising. This follows many years of research elucidating mechanisms of action and utility of DCregs. Herein, we review early-phase clinical trial observations and recent advances in the production, modification, and future-trajectory of DCreg in organ transplantation.

Recent findings: Preclinical work has demonstrated the ability of adoptively transferred DCreg to abrogate ischemia-reperfusion injury and promote long-term allograft survival. Good Manufacturing Practice-grade DCregs have been generated in adequate numbers for early-phase trials of autologous DCregs in kidney transplantation and donor-derived DCreg in liver transplantation. These trials have demonstrated feasibility and safety, with preliminary evidence of an influence on host immune reactivity. In both kidney and liver transplantation, reduced effector CD8 + T-cells have been noted, together with other changes that may be conducive to reduced dependence on immunosuppressive therapy.

Summary: Substantial progress has been made in bringing DCreg to clinical testing in organ transplantation. Additional clinical and mechanistic studies are now needed to further explore and garner the full potential of DCreg in organ transplantation.

Purpose of review: This review focuses on more recently emerging rejection phenotypes in the context of time post transplantation and the resulting differential diagnostic challenges. It also discusses how novel ancillary diagnostic tools can potentially increase the accuracy of biopsy-based rejection diagnosis.

Recent findings: With advances in reducing immunological risk at transplantation and improved immunosuppression treatment renal allograft survival improved. However, allograft rejection remains a major challenge and represent a frequent course for allograft failure. With prolonged allograft survival, novel phenotypes of rejection are emerging, which can show complex overlap and transition between cellular and antibody-mediated rejection mechanisms as well as mixtures of acute/active and chronic diseases. With the emerging complexity in rejection phenotypes, it is crucial to achieve diagnostic accuracy in the individual patient.

Summary: The prospective validation and adoption of novel molecular and computational diagnostic tools into well defined and appropriate clinical context of uses will improve our ability to accurately diagnose, stage, and grade allograft rejection.

Purpose of review: Urine CXCL10 is a promising biomarker for posttransplant renal allograft monitoring but is currently not widely used for clinical management.

Recent findings: Large retrospective studies and data from a prospective randomized trial as well as a prospective cohort study demonstrate that low urine CXCL10 levels are associated with a low risk of rejection and can exclude BK polyomavirus replication with high certainty. Urine CXCL10 can either be used as part of a multiparameter based risk assessment tool, or as an individual biomarker taking relevant confounders into account. A novel Luminex-based CXCL10 assay has been validated in a multicenter study, and proved to be robust, reproducible, and accurate.

Summary: Urine CXCL10 is a well characterized inflammation biomarker, which can be used to guide performance of surveillance biopsies. Wide implementation into clinical practice depends on the availability of inexpensive, thoroughly validated assays with approval from regulatory authorities.

Purpose of review: Bacteria are the leading cause of infections in solid organ transplant (SOT) recipients, significantly impacting patient outcome. Recently detailed and comprehensive epidemiological data have been published.

Recent finding: This literature review aims to provide an overview of bacterial infections affecting different types of SOT recipients, emphasizing underlying risk factors and pathophysiological mechanisms.

Summary: Lung transplantation connects two microbiotas: one derived from the donor's lower respiratory tract with one from the recipient's upper respiratory tract. Similarly, liver transplantation involves a connection to the digestive tract and its microbiota through the bile ducts. For heart transplant recipients, specific factors are related to the management strategies for end-stage heart failure based with different circulatory support tools. Kidney and kidney-pancreas transplant recipients commonly experience asymptomatic bacteriuria, but recent studies have suggested the absence of benefice of routine treatment. Bloodstream infections (BSI) are frequent and affect all SOT recipients. Nonorgan-related risk factors as age, comorbidity index score, and leukopenia contribute to BSI development. Bacterial opportunistic infections have become rare in the presence of efficient prophylaxis. Understanding the epidemiology, risk factors, and pathophysiology of bacterial infections in SOT recipients is crucial for effective management and improved patient outcomes.

Purpose of review: Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT).

Recent findings: Universal prophylaxis and preemptive therapy are the most adopted strategies for prevention of CMV disease globally. Prophylaxis with valganciclovir is the most widely used approach to CMV prevention, however leukopenia and late onset CMV disease after discontinuation of prophylaxis requires new strategies to prevent this complication. The use of assays detecting CMV-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Letermovir has been recently approved for prophylaxis in kidney transplant recipients. CMV-RNAemia used together with CMV-DNAemia in the viral surveillance of CMV infection provides accurate information on viral load kinetics, mostly in patients receiving letermovir prophylaxis/therapy. The development of refractory and resistant CMV infection remains a major challenge and a new treatment with maribavir is currently available. In the present paper we will review the most recent advances in prevention and treatment of CMV diseases in SOT recipients.

Summary: Recent findings, summarized in the present paper, may be useful to optimize prevention and treatment of CMV infection in SOT.