Current Opinion in Organ Transplantation最新文献

Purpose of review: Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field.

Recent findings: Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging.

Summary: Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.

Purpose of review: Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology.

Recent findings: Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection.

Summary: While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.

Purpose of review: This review aims to summarize recent changes in the cardiac evaluation of adult liver transplant candidates. Over the last several years, there have been significant advances in the use of coronary computed tomography angiography (CCTA) with and without fractional flow reserve (FFR) and increasingly widespread availability of coronary calcium scoring for risk stratification for obstructive coronary artery disease. This has led to novel strategies for risk stratification in cirrhotic patients being considered for liver transplant and an updated American Heart Association (AHA) position paper on the evaluation of liver and kidney transplant candidates. The diagnosis of cirrhotic cardiomyopathy has been refined. These new diagnostic criteria require that specific echocardiographic parameters are evaluated in all patients. The definition of pulmonary hypertension on echocardiography has been altered and no longer utilizes right atrium (RA) pressure estimates based on inferior vena cava (IVC) size and collapse. This provides more volume neutral estimates of pulmonary pressure.

Recent findings: Although CCTA has outstanding negative predictive value, false positive results are not uncommon and often lead to further testing. Revised diagnostic criteria for cirrhotic cardiomyopathy improve risk stratification for peri-operative volume overload and outcomes. Refined pulmonary hypertension criteria provide improved guidance for right heart catheterization (RHC) and referral to subspecialists. There are emerging data regarding the safety and efficacy of TAVR for severe aortic stenosis in cirrhotic patients.

Summary: Increased utilization of noninvasive testing, including CCTA and/or coronary calcium scoring, can improve the negative predictive value of testing for obstructive coronary artery disease and potentially reduce reliance on coronary angiography. Application of the 2020 criteria for cirrhotic cardiomyopathy will improve systolic and diastolic function assessment and subsequent perioperative risk stratification. The use of global strain scores is emphasized, as it provides important information beyond ejection fraction and diastolic parameters. A standardized one-parameter echo cut-off for elevated pulmonary pressures simplifies both evaluation and follow-up. Innovative transcutaneous techniques for valvular stenosis and regurgitation offer new options for patients at prohibitive surgical risk.

Purpose of review: Exercise training programs are an integral part of the management of solid organ transplantation (SOT) candidates and recipients. Despite this, they are not widely available and specific guidelines on exercise parameters for each type of organ are not currently provided. A review of this topic could help clinicians to prescribe appropriate exercise regimens for their patients.

Recent findings: In this narrative review, we discuss the physical impairments of SOT candidates and recipients and how these affect their physical function and transplant outcomes. We examine recent systematic reviews, statements, and randomized controlled trials on exercise training in SOT candidates and recipients and present the current available evidence while providing some practical recommendations for clinicians based on the frequency, intensity, time, and type principle.

Summary: While randomized controlled trials of better methodology quality are needed to strengthen the evidence for the effects of exercise training and for the optimal training characteristics, the available evidence points to beneficial effects of many different types of exercise. The current evidence can provide some guidance for clinicians on the prescription of exercise training for transplant candidates and recipients.

Purpose of review: With changing donor characteristics (advanced age, obesity), an increase in the use of extended criteria donor (ECD) livers in liver transplantation is seen. Machine perfusion allows graft viability assessment, but still many donor livers are considered nontransplantable. Besides being used as graft viability assessment tool, ex situ machine perfusion offers a platform for therapeutic strategies to ameliorate grafts prior to transplantation. This review describes the current landscape of graft repair during machine perfusion.

Recent findings: Explored anti-inflammatory therapies, including inflammasome inhibitors, hemoabsorption, and cellular therapies mitigate the inflammatory response and improve hepatic function. Cholangiocyte organoids show promise in repairing the damaged biliary tree. Defatting during normothermic machine perfusion shows a reduction of steatosis and improved hepatobiliary function compared to nontreated livers. Uptake of RNA interference therapies during machine perfusion paves the way for an additional treatment modality.

Summary: The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.

Purpose of review: The role of nutrition in organ health including solid organ transplantation is broadly accepted, but robust data on nutritional regimens remains scarce calling for further investigation of specific dietary approaches at the different stages of organ transplantation. This review gives an update on the latest insights into nutritional interventions highlighting the potential of specific dietary regimens prior to transplantation aiming for organ protection and the interplay between dietary intake and gut microbiota.

Recent findings: Nutrition holds the potential to optimize patients' health prior to and after surgery, it may enhance patients' ability to cope with the procedure-associated stress and it may accelerate their recovery from surgery. Nutrition helps to reduce morbidity and mortality in addition to preserve graft function. In the case of living organ donation, dietary preconditioning strategies promise novel approaches to limit ischemic organ damage during transplantation and to identify the underlying molecular mechanisms of diet-induced organ protection. Functioning gut microbiota are required to limit systemic inflammation and to generate protective metabolites such as short-chain fatty acids or hydrogen sulfide.

Summary: Nutritional intervention is a promising therapeutic concept including the pre- and rehabilitation stage in order to improve the recipients' outcome after solid organ transplantation.

Purpose of review: In this review, we discuss the development of the Liver Frailty Index (LFI) and how it may serve as a model for developing other organ-specific frailty indices.

Recent findings: As the demand for solid organ transplants continues to increase, the transplantation community is enhancing its strategies for organ allocation to gain deeper insights into patient risk profiles and anticipated outcomes. Frailty has emerged as a critical concept in transplant care, offering valuable insights into adverse health outcomes. Standardizing frailty assessment across transplant programs could enhance prognostic accuracy and inform pretransplant interventions.The LFI comprises of three performance-based tests that each represents essential components of the multidimensional frailty construct. This composite metric provides insights beyond liver function and considers nonhepatic comorbid factors. Identifying common frailty principles among all transplant candidates and adopting the LFI methodology, which assesses fundamental frailty principles using liver-specific tools, could establish a foundational pool of shared core frailty principles. From this pool, organ-specific frailty indices could be derived, each equipped with the clinically relevant organ-specific tools to evaluate common core principles.

Summary: Creating a standardized framework across all solid-organ transplants, with common principles and organ-specific measurements, would facilitate consistent frailty assessment, standardize the integration of the frailty construct into transplant decision-making, and enable center-level interventions to improve outcomes for patients with end-stage organ disease.

Purpose of review: In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function.

Recent findings: Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy.

Summary: Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.

Purpose of review: The aim of the current review is to highlight the importance of exercise training as an important section of transplant recipient rehabilitation process and explain the role of the exercise scientist in the development, implementation, and assessment of the exercise regime.

Recent findings: Transplant patients face a unique set of challenges in their recovery and rehabilitation process, often requiring a multifaceted approach to address the physical, emotional, and psychological aspects of their condition. Exercise training has emerged as a crucial component in the care of these patients, providing a means to improve functional capacity, enhance quality of life, and mitigate the adverse effects of transplant-related complications. Exercise scientists who are trained to assess patient's physical limitations, develop and deliver personalized exercise programs, and monitor their progress are uniquely positioned to play a crucial role in the treatment of patients with chronic conditions that require exercise training as a mean of improving and maintaining health and quality of life.

Summary: Exercise scientists are the appropriate professionals for providing transplant recipients with the recommended exercise training for maintaining and improving their health status as part of the overall plan of long-term care and support.

Purpose of review: Normothermic regional perfusion (NRP) is a novel procurement technique for donation after circulatory death (DCD) in the United States. It was pioneered by cardiothoracic surgery programs and is now being applied to abdominal-only organ donors by abdominal transplant programs.

Recent findings: Liver and kidney transplantation from thoracoabdominal NRP (TA-NRP) donors in the United States was found to have lower rates of delayed kidney graft function and similar graft and patient survival versus recipients of cardiac super rapid recovery (SRR) DCD donors. The excellent outcomes with NRP have prompted the expansion of NRP technology to abdominal transplant programs.

Summary: Excellent early outcomes with liver and kidney transplantation have prompted the growth of NC-NRP procurement for abdominal-only DCD donors across the US, and now requires standardization of technical and nontechnical aspects of this procedure.