Transplantation Reviews最新文献

Hypothermic Oxygenated machine PErfusion (HOPE) has recently emerged as a preservation technique which can reduce ischemic injury and improve clinical outcomes following liver transplantation. First developed with the advent solid organ transplantation techniques, hypothermic machine perfusion largely fell out of favour following the development of preservation solutions which can satisfactorily preserve grafts using the cheap and simple method, static cold storage (SCS). However, with an increasing need to develop techniques to reduce graft injury and better utilise marginal and donation after circulatory death (DCD) grafts, HOPE has emerged as a relatively simple and safe technique to optimise clinical outcomes following liver transplantation. Perfusing the graft with cold, acellular, oxygenated perfusate either via the portal vein (PV) alone, or via both the PV and hepatic artery (HA), HOPE is generally commenced for a period of 1–2 h immediately prior to implantation. The technique has been validated by multiple randomised control trials, and pre-clinical evidence suggests HOPE primarily reduces graft injury by decreasing the accumulation of harmful mitochondrial intermediates, and subsequently, the severity of post-reperfusion injury. HOPE can also facilitate real time graft assessment, most notably via the measurement of flavin mononucleotide (FMN) in the perfusate, allowing transplant teams to make better informed clinical decisions prior to transplantation. HOPE may also provide a platform to administer novel therapeutic agents to ex situ organs without risk of systemic side effects. As such, HOPE is uniquely positioned to revolutionise how liver transplantation is approached and facilitate optimised clinical outcomes for liver transplant recipients.

Aims

Tacrolimus (Tac) is commonly prescribed in solid organ transplantation to prevent immune-mediated damage to the graft. However, its pharmacokinetics show substantial variability between and within patients. Intra-patient variability of tacrolimus (Tac-IPV) has emerged as a novel marker to predict transplant outcomes. Numerous studies report varying associations between Tac-IPV and clinical outcomes, with Tac-IPV measures showing wide discrepancies among these studies. This inconsistency could be a significant factor that influences the various outcomes reported in different studies. Our review comprehensively assesses the relationship between various Tac-IPV measures and their associations with clinical outcomes in transplant patients.

Methods

A comprehensive literature search was conducted using the PubMed and Embase databases, covering the period from 2004 to March 31, 2023. The search focused on studies that examined the relationship between Tac-IPV and clinical outcomes in kidney transplantation (KT). The inclusion criteria were specific to studies addressing Tac-IPV, including measures such as standard deviation (SD), coefficient of variation (CV), time-weighted coefficient of variability (CV), mean absolute deviation (MAD), and Tac variability score (TVS). Clinical outcomes included the development of de novo donor-specific antibodies (dnDSA), rejection episodes, graft loss, and graft failure.

Results

Among the 33 studies that met the inclusion criteria, a notable proportion presented conflicting findings in their assessment of various Tac-IPV measures regarding dnDSA, rejection episodes, graft loss, and graft failure.

Conclusions

Most studies have identified a correlation between high Tac-IPV and poor clinical outcomes; however, this relationship is multifactorial. Influencing factors include the metabolic status of KT patients, the timing of Tac-IPV calculations, and the criteria for defining high and low Tac-IPV thresholds, including the size and selection method. CV, MAD, and TWCV are the metrics that are most frequently used to determine Tac-IPV. Additionally, most of the methods for establishing Tac-IPV thresholds typically employ receiver operating characteristic (ROC) curves and median values. It is also notable that studies examining the clinical significance of Tac-IPV often include tacrolimus levels measured six months after kidney transplantation.

Rat orthotopic liver transplantation (ROLT) serves as an ideal animal model and has gained popularity in addressing complications and perioperative treatments related to clinical liver transplantation. Through extensive research on ROLT model construction, the conventional “two-cuff” method has gradually become established. However, traditional methods still present challenges including limited visual field during vascular suturing, vascular torsion, biliary tract injuries, and prolonged anhepatic periods. Consequently, this paper aims to review the latest advancements and various techniques in this field, providing a valuable reference for individuals interested in constructing ROLT models.

Background

Current guidelines lack consensus on whether antiviral prophylaxes should be administered after kidney transplantation from HBcAb+ donors. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of de novo HBV (DNH) infection, as well as graft and patient survival.

Methods

We searched PubMed, Embase, and the Cochrane Library up to December 31, 2023. We included relevant studies that assessed clinical outcomes following transplantation utilizing HBcAb+ kidneys. Summary measures of effect and 95% confidence intervals (CI) for prevalence, risk factors, as well as graft and patient survival were estimated using random-effects meta-analysis.

Results

Thirteen studies were included for the final analysis. The DNH incidence was at 0.36% (9/2516) with low heterogeneity (I² = 6%). HBsAb+ recipients (OR: 0.78, 95%CI: 0.25–2.38), HBcAb+ recipients (OR: 3.11, 95%CI: 0.91–10.66, P = 0.071), and recipients not receiving any antiviral prophylaxis (OR: 1.26, 95%CI: 0.15–10.58) were not associated with higher DNH risk. Specifically, HBsAb-/HBcAb+ recipients had the highest DNH incidence (4.65%), followed by HBsAb-/HBcAb- (0.49%), HBsAb+/HBcAb- recipients (0.45%), and HBsAb+/HBcAb+ (0%). Furthermore, recipients receiving HBcAb+ kidneys had comparable graft survival (HR: 1.06, 95%CI: 0.94–1.19, P = 0.55) and patient survival (HR:1.16, 95%CI: 0.98–1.38, P = 0.090) compared with recipients receiving HBcAb- kidneys.

Conclusion

Kidney transplantation utilizing HBcAb+ kidneys contributed to comparable graft and patient survival with an extremely low risk of HBV transmission. Antiviral prophylaxes may only be administered in HBsAb-/HBcAb+ recipients.

Background & Aims

Echocardiographic findings may provide valuable information about the cardiac conditions in cirrhotic patients waiting for liver transplantation (LT). However, data on the ability of the different echocardiographic parameters to predict post-transplant risk of mortality are scarce and heterogeneous. This systematic review evaluates the role of different echocardiographic features as predictors of post-LT mortality. A meta-analysis was also performed according to the observed results.

Methods

A systematic review was conducted according to PRISMA guidelines. Medline (PubMed) database was searched through February 2023 for relevant published original articles reporting the prognostic value of echocardiographic findings associated with outcomes of adult LT recipients. The risk of bias in included articles was assessed using ROBINS-E tool. Methodological quality varied from low to high across the risk of bias domains.

Results

Twenty-three studies were identified after the selection process; ten were enrollable for the meta-analyses. According to the results observed, the E/A ratio fashioned as a continuous value (HR = 0.43, 95%CI = 0.25–0.76; P = 0.003), and tricuspid regurgitation (HR = 2.36, 95%CI = 1.05–5.31; P = 0.04) were relevant predicting variables for post-LT death. Other echocardiographic findings failed to merge with statistical relevance.

Conclusion

Tricuspid regurgitation and left ventricular diastolic dysfunction play a role in the prediction of post-LT death. More studies are needed to clarify further the impact of these echocardiographic features in the transplantation setting.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources.

While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation.

A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes.

Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation.

Background

Frailty, malnutrition and sarcopenia lead to a significant increase in morbidity and mortality before and after liver transplantation (LT). Prehabilitation attempts to optimize physical fitness of individuals before major surgeries. To date, little is known about its impact on patients awaiting LT.

Aims

The aim of our scoping review was to describe whether prehabilitation in patients awaiting LT is feasible and safe, and whether it leads to a change in clinical parameters before or after transplantation.

Methods

We performed a systematic review of the literature from 1946 to November 2023 to identify prospective studies and randomized controlled trials of adult LT candidates who participated in an exercise training program.

Results

Out of 3262 citations initially identified, six studies were included. Studies were heterogeneous in design, patient selection, intervention, duration, and outcomes assessed. All studies were self-described as pilot or feasibility studies and had a sample size ranging from 13 to 33. Two studies were randomized controlled trials. Two study restricted to patients with cirrhosis who were eligible for liver transplantation or on the transplant list. Exercise programs lasted between 6 and 12 weeks. In terms of feasibility, proportion of eligible patients that were recruited was between 54 and 100%. Program completion ranged between 38 and 90%. Interventions appeared safe with 9 (9.2%) adverse events noted. In the intervention group, improvements were generally noted in peak oxygen consumption and workload, 6-min walking distance, and muscle strength. One study suggested a decrease in post-transplant hospital length of stay.

Conclusions

Overall, it appears that prehabilitation with exercise training is feasible, and safe in patients awaiting LT. Higher quality and larger studies are needed to confirm its impact on pre- and post-transplantation-related outcomes.

Purpose

We aimed to identify the condition- and transplant-specific patient-reported outcome measures (PROMs) available to measure quality of life (QoL) in solid organ transplant (SOT) recipients, examine their development and content, and critically appraise the quality of their measurement properties, to inform recommendations for clinical and research use.

Methods

We systematically searched MEDLINE, Embase, CINAHL, PsycINFO, Cochrane CENTRAL, and Scopus from inception to 27th January 2023. Search hits were screened for eligibility by two independent reviewers; papers reporting the development and/or validation of condition- and transplant-specific PROMs measuring QoL in adult SOT recipients were considered eligible. We abstracted and synthesised data on PROM characteristics, development (item generation and/or reduction), and content (QoL dimensions). Quality appraisal and synthesis were informed by the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines, and included methodological and quality assessment of measurement properties, GRADE levels of evidence, feasibility and interpretability.

Results

We identified 33 papers reporting 26 QoL PROMs validated in SOT recipients (kidney n = 10 PROMs; liver n = 6; lung n = 3; heart n = 2; pancreas n = 1; multiple organs n = 4). Patient discussions (n = 17 PROMs) and factor analysis (n = 11) were the most common item generation and reduction techniques used, respectively. All PROMs measured ≥3 of nine QoL dimensions (all measured emotional functioning); KDQoL-SF and NIDDK-QA measured all nine. Methodological quality was variable; no PROM had low evidence or better for all measurement properties. All PROMs were COSMIN recommendation category ‘B', primarily because none had sufficient content validity.

Conclusions

There are many condition- and transplant-specific QoL PROMs validated in SOT recipients, particularly kidney. These findings can help inform PROM selection for clinicians and researchers. However, caution is required when adopting measures, due to the substantial heterogeneity in development, content, and quality. Each PROM has potential but requires further research to be recommendable. Greater consideration of patient and professional involvement in PROM development in this setting is needed to ensure sufficient content validity.