Single cell RNA-sequencing delineates CD8+ tissue resident memory T cells maintaining rejection in liver transplantation.

Rationale: Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. Methods: This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. Results: Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8+ TRMs within rejected grafts compared to stable ones. The elevated presence of CD8+ TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8+ TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. Conclusions: These insights into the distinctive activation and interaction patterns of CD8+ TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes.

The Cost of Procuring Deceased Donor Livers: Evidence From US Organ Procurement Organization Cost Reports, 2013-2018.

Deceased donor organs for transplantation are costly. Expenses include donor assessment, pre-operative care of acceptable donors, surgical organ recovery, preservation and transport, and other costs. US Organ Procurement Organizations (OPOs) serve defined geographic areas in which each OPO has exclusive organ recovery responsibilities including detailed reporting of costs. We sought to determine the costs of procuring deceased donor livers by examining reported organ acquisition costs from OPO cost reports. Using 6 years of US OPO cost report data for each OPO (2013-2018), we determined the average cost of recovering a viable (i.e., transplanted) liver for each of the 51 independent US OPOs. We examined predictors of these costs including the number of livers procured, the percent of nonviable livers, direct procurement costs, coordinator salaries, professional education, and local cost of living. A cost curve estimated the relationship between the cost of livers and the number of locally procured livers. The average cost of procured livers by individual OPO-year varied widely from $11 393 to $65 556 (average $31 659) over the six study years. An increase in the overall number of procured livers was associated with lower direct costs, administrative, and procurement overhead costs, but this association differed for imported livers. Cost per local liver decreased linearly for each additional liver, while importing more livers was only cost saving until 200 livers, with imported livers costing more ($39K vs. $31.7K). The largest predictor of variation in cost was the aggregate of direct costs (e.g., hospital costs) to recover the organ (57%). Cost increases were 2.5% per year (+$766/year). This information may be valuable in determining how OPOs might improve service to transplant centers and the patients they serve.

The effectiveness of exercise prehabilitation on aerobic capacity, muscle strength and body composition in patients with cirrhosis awaiting liver transplantation: a systematic review and meta-analysis protocol.

INTRODUCTION: Cirrhosis is the main cause of morbidity and mortality globally, accounting for approximately 1.2 million deaths annually. Impaired aerobic capacity, muscle wasting and reduced muscle strength are significant complications in patients with cirrhosis. Preoperative exercise intervention "prehabilitation" has been recognised as a potential approach to optimise muscle strength, aerobic capacity and body composition as well as quality of life in patients awaiting abdominal surgery. However, there is little evidence on the effects of preoperative exercise on older adults with cirrhosis and awaiting liver transplant. Thus, the primary objective of this systematic review and meta-analysis will be to assess the effects of exercise interventions in improving aerobic capacity, muscle strength and body composition of older adults with cirrhosis and awaiting liver transplant. METHODS AND ANALYSIS: This systematic review and metaanalysis protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will include all peer-reviewed randomised controlled trials (RCTs), including cluster RCTs, controlled (non-controlled), complex clinical trials (CCTs) or cluster trials, cohort, observational studies published in English from inception until July 2024. The following electronic databases will be searched: MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO) and Scopus (Elsevier) and supplemented by a secondary screening of the reference lists of all included articles. Searches will involve studies with both male and female participants aged ≥ 18 years with cirrhosis and awaiting liver transplant. Primary outcomes will include muscle strength, and aerobic capacity. The secondary outcomes include body composition (e.g. body mass index, and thigh circumference). The Cochrane Collaboration Risk of Bias Tool will be used to evaluate quality of the studies and Review Manager (RevMan) V.5.3 (Copenhagen, Denmark: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Effect sizes will be expressed as a standardised mean difference, and their 95% confidence intervals will be calculated and presented as a forest plot. The standard χ2 and I2 tests will be used to test heterogeneity. CONCLUSION: This systematic review and meta-analysis is anticipated to provide meaningful and contemporary evidence on the effects of preoperative exercise in older adults living with cirrhosis and awaiting liver transplant. In addition, the findings will help clinicians with developing safe and effective preoperative exercise regimens for these patients.

On achieving gender equity within the liver transplantation medical and surgical workforce.

Until relatively recently there has been a paucity of readily available information pertaining to the demographics of the medical and surgical workforces for the subspecialty of liver transplantation. This is relevant as it relates to whether gender equity is now being achieved across this particular workforce. This manuscript focuses on what eventually led to the recognition that more comprehensive data were required along with what is now actually known with respect to the gender ratios of the liver transplant workforce along with their related academic activities. Potential solutions to address any ongoing imbalances are also examined. The extent and range of gender disparities previously reported for other cohorts of physicians and surgeons, are also apparent amongst the liver transplant workforce in most regions of the world. This also pertains to the higher leadership positions within liver transplant centers as well as for the related editorial and scientific congress roles. Common themes/recommendations are now emerging as to how best to address the lack of progress towards gender equity. These include the development and implementation of policies, the removal of barriers to career progression, and proper governance. Ongoing actions are going to be required to achieve gender equity across the workforce in liver transplantation around the world.

Fairness and pitfalls of the Italian waiting list for elective liver transplantation: The ECALITA registry study.

BACKGROUND: The challenge of transplant waiting-lists is to provide organs for all candidates while maintaining efficiency and equity. AIMS: We investigated the probability of being transplanted or of waiting-list dropout in Italy. METHODS: Data from 12,749 adult patients waitlisted for primary liver-transplantation from January 2012 to December 2022 were collected from the National Transplant-Registry.The cohort was divided into Eras:1 (2012-2014);2 (2015-2018);and 3 (2019-2022). RESULTS: The one-year probability of undergoing transplant increased (67.6 % in Era 1vs73.8 % in Era 3,p < 0001) with a complementary 46 % decrease in waiting-list failures. Patients with hepatocellular-carcinoma were transplanted more often than cirrhotics[at model for end-stage liver-disease (MELD)-15:HR = 1.28,95 %CI:1.21-1.35;at MELD-25:HR = 1.04,95 %CI:0.92-1.19) and those with other indications (at MELD-15:HR = 1.27,95 %CI:1.11-1.46) across all eras. Candidates with Hepatitis-B-virus (HBV)related disease had a greater probability of transplant than those with Hepatitis-C virus-related (HR = 1.13,95 %CI:1.07-1.20), alcohol-related (HR = 1.13,95 %CI:1.05-1.21), and metabolic-related (HR = 1.18,95 %CI:1.09-1.28)disease. Waiting-list failures increased by 27 % every 5 MELD-points and by 14 % for every 5-year increase in recipient-age and decreased by 10 % with each 10-cm increase in stature. Blood-group O patients showed the highest probability of waiting-list failure (HR = 1.28,95 %CI:1.15-1.43). CONCLUSIONS: Liver-transplantation waiting-list success-rates have significantly improved in Italy, with patients with hepatocellular-carcinoma and/or HBV-related diseases being favored. High MELD-score, old-age, short-stature, and blood-group O were significant risk-factors for waiting-list failure. Efforts to improve organ-allocation and prioritization-policies are underway.

Case Report: A case of immune hemolytic anemia after liver transplantation: passenger lymphocyte syndrome is the culprit.

Passenger lymphocyte syndrome (PLS) is most commonly observed after solid organ transplantation with minor ABO blood group incompatibility. It consists of a set of clinical symptoms brought on by the remaining lymphocytes of the donor organ developing antibodies against the recipient's antigens. Here, we describe a typical case of PLS in a type A+ recipient receiving a liver transplant from a type O+ donor. She suffered from jaundice, abnormally decreased hemoglobin level, and severe hemolytic anemia without bleeding. During hemolysis, we detected a positive direct antiglobulin test (DAT), and the thermal elution test revealed the presence of IgG anti-A antibodies in her serum. When immunosuppressive agents and blood transfusion were used together, cross-matched O+ washing red blood cells led to an expected outcome without side effects.

Population pharmacokinetics study of tacrolimus in liver transplant recipients: a comparison between patients with or without liver cancer before surgery.

Background and Objective: The main challenge for immunosuppressive therapy using tacrolimus in liver transplantation is the considerable variability in its oral bioavailability and the narrow treatment range. Many population pharmacokinetic (PopPK) models have been established to precisely estimate the PK variability of tacrolimus in liver transplant recipients. However, it remains unclear whether there is a significant difference in the PK behavior of tacrolimus between patients with or without liver cancer before surgery. Therefore, we aimed to compare the differences of PK parameters and simulate exposures of tacrolimus between populations preoperatively diagnosed with liver cancer or not by PopPK modeling. Methods: In total, 802 blood concentrations of tacrolimus from 196 patients (118 liver cancer and 78 non-liver-cancer samples) were included in this study. Demographic data and clinical parameters were integrated to perform a PopPK analysis using the nonlinear mixed-effects modeling approach. Potential covariates were evaluated by using a stepwise method. Goodness-of-fit plot and bootstrap were performed to assess the model stability and predictive performance. Simulations were introduced to optimize dosing regimens of both the liver cancer and non-liver-cancer groups according to the guidance. Results: The PK of tacrolimus was best described by a one-compartment model with first-order absorption and linear elimination, with weight and direct bilirubin as the significant covariates. In the process of constructing the basic model, we tried to separately estimate the PK parameters in liver cancer and non-liver-cancer populations. The results showed that the PK parameters in the two populations were similar, and the individual variation in Ka in non-liver-cancer subjects was large. Hence, the final model did not distinguish between the two populations. Moreover, a minor increase of less than 10% was observed in the simulated exposure in the patients preoperatively diagnosed with liver cancer compared with that in non-liver-cancer groups. Conclusion: The established PopPK model was capable of optimizing tacrolimus dosing in whole populations who underwent liver transplantation. Although a minimal difference was found in tacrolimus exposure between the liver cancer and non-liver-cancer groups, more research is warranted to explore the differences between the two populations in the future, given the potential limitations of this study.

Assessment of liver graft quality during hypothermic oxygenated perfusion: the first international validation study.

BACKGROUND AND AIM: While it is currently assumed that liver assessment is only possible during normothermic machine perfusion (NMP), there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation. STUDY DESIGN: Perfusate samples of human livers from 10 centers in 7 countries with HOPE-experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivates and inflammatory markers. Perfusate FMN was correlated with graft loss due to primary non-function or symptomatic non-anastomotic biliary strictures (NAS), and kidney failure, as well as liver injury after transplantation. Livers deemed unsuitable for transplantation served as negative control. RESULTS: We collected 473 perfusate samples of human DCD (n=315) and DBD livers (n=158). Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R=0.7011,p<0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418 (95%CI 0.7466-0.9370,p<0.0001), c-statistic fluorometry 0.7733 (95%CI 0.7006-0.8461,p<0.0001). Perfusate FMN values were also significantly correlated with symptomatic NAS and kidney failure, and superior in prediction of graft loss when compared to conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release. CONCLUSIONS: This first international study validates the predictive value of the mitochondrial co-factor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation. IMPACT AND IMPLICATIONS: Analysis of 473 perfusates, collected from 10 international centers during hypothermic oxygenated perfusion (HOPE), revealed that mitochondria derived flavin mononucleotide (FMN) values in perfusate is predictive for graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex-situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

It's Not Always Infections When It Comes to Resource-Poor Countries: A Fascinating Case Report.

A patient's demographics often guide healthcare providers toward clues to a diagnosis. A recent travel history becomes an essential piece of the puzzle when there is a high suspicion of an infectious cause. When a patient walks into the hospital after having traveled to or from a resource-poor country with systemic afflictions, a physician's mind quickly jumps to infectious causes, and in most circumstances, it proves to be correct. We report an interesting case of a 28-year-old male from Guatemala who experienced acute gastrointestinal (GI) symptoms. Previous research in this field has shown that patients with inflammatory bowel disease (IBD) are prone to a slew of GI infections. Interestingly, our patient's presenting symptoms were initially attributed to "infections," but a thorough investigation revealed an unexpected twist of events. Our patient presented with multiple GI infections after the usual triggers, which masqueraded the coexistence of underlying primary sclerosing cholangitis and ulcerative colitis for a short course but were diagnosed promptly after a thorough workup.

Predictive performance of Metagenomic Next Generation Sequencing in early detection of post-liver transplantation infections.

Objective: To evaluate the predictive performance of metagenomic next-generation sequencing (mNGS) in identifying and predicting pulmonary infections following liver transplantation and to investigate its association with patient outcomes within the initial four-week post-transplantation period. Methods: We retrospectively analyzed 41 liver transplant patients with suspected pulmonary infections from August 2022 to May 2023. Bronchoalveolar lavage fluid (BALF) samples were collected on the first postoperative day for metagenomic next generation sequencing (mNGS) and culture. The predictive capability of mNGS for subsequent infections was assessed by monitoring inflammatory biomarkers and comparing the detection rates with culture methods. Real-time Polymerase Chain Reaction (Rt-PCR) was used to monitor Human betaherpesvirus 5 (CMV) and Human parvovirus B19 (B19) weekly during a four-week postoperative period. Inflammatory biomarkers and blood coagulation function were evaluated on specific days throughout the first, third, fifth, and during four weeks following surgery. The study was conducted until August 2023 to evaluate the patients' prognostic survival outcome, classifying them into groups based on the mortality and survival. Results: The analysis included a total of 41 patients, comprising 32 males and 9 females, with an average age of 52 (47, 63) years. Within one week after liver transplantation, there were 7 cases of bacterial infections, 5 cases of fungal infections, 19 cases of mixed infections, 8 cases without any infection, and 2 cases with unidentified pathogen-associated infections. mNGS successfully predicted 39 (72 %) strains of pathogens, while culture-based methods only detected 28 (52 %) strains. Among the 8 patients diagnosed as non-infected, culture methods identified positive results in 4 cases (50 %), whereas mNGS yielded positive results in 7 cases (87.5 %). The detection rates of CMV and B19 by Rt-PCR within 4 weeks after liver transplantation were 61 % and 17 %, respectively (25/41, 7/41) among the patients. During the study period, a total of 9 patients succumbed while 32 patients survived. The death group and the survival group exhibited significant differences in CRP, HGB, and INR levels at specific monitoring time points. The proportion of CMV detection in blood was significantly higher in the death group compared to the surviving group. Elevated CRP level was identified as a prognostic risk factor. Conclusions: Despite the presence of false positives, mNGS still presents a potential advantage in predicting pulmonary infection pathogens following liver transplantation. Furthermore, the levels of CRP and CMV carrier status within four weeks post-surgery exhibit significant associations with patient survival and prognosis.

A Predictive Model of Pressure Injury in Children Undergoing Living Donor Liver Transplantation Based on Machine Learning Algorithm.

AIMS: The aim of our study was to formulate and validate a prediction model using machine learning algorithms to forecast the risk of pressure injuries (PIs) in children undergoing living donor liver transplantation (LDLT). DESIGN: A retrospective cohort study. METHODS: The research was carried out at China's largest paediatric liver transplantation centre. A total of 438 children who underwent LDLT between June 2021 and December 2022 constituted the study cohort. The dataset was partitioned randomly into 70% for training datasets (306 cases) and 30% for testing datasets (132 cases). Utilising four machine learning algorithms-Decision Tree, Random Forest, Gradient Boosting Decision Tree and eXtreme Gradient Boosting-we identified risk factors and constructed predictive models. RESULTS: Out of 438 children, 42 developed PIs, yielding an incidence rate of 9.6%. Notably, 94% of these cases were categorised as Stage 1, and 54% were localised on the occiput. Upon evaluating the four prediction models, the Decision Tree model emerged as the most effective. The primary contributors to pressure injury in the Decision Tree model were identified as operation time, intraoperative corticosteroid administration, preoperative skin protection measures and preoperative skin conditions. A visualisation elucidating the logical inference process for the 10 variables within the Decision Tree model was presented. Ultimately, based on the Decision Tree model, a predictive system was developed. CONCLUSION: Machine learning algorithms facilitate the identification of crucial factors, enabling the creation of an effective Decision Tree model to forecast pressure injury development in children undergoing LDLT. IMPACT: With this predictive model at their disposal, nurses can assess the pressure injury risk level in children more intuitively. Subsequently, they can implement tailored preventive strategies to mitigate the occurrence of PIs. PATIENT OR PUBLIC CONTRIBUTION: Paediatric patients contributed electronic health records datasets.

Waitlist and transplant outcomes in patients with metabolic dysfunction-associated steatotic liver disease and autoimmune hepatitis.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), in the context of autoimmune hepatitis (AIH) among liver transplantation (LT) candidates or recipients remains poorly understood. This study compares waitlist and post-LT outcomes in patients with MASLD/AIH to MASLD and AIH alone. METHODS: Using the united network organ sharing database (2002-2022), we compared waitlist outcomes and post-LT survival among patients with MASLD/AIH (n = 282), AIH (n = 5812), and MASLD (n = 33 331). Competing risk, Kaplan Meier estimates and Cox proportional hazard analyses were performed. RESULTS: MASLD/AIH group had the highest rates of encephalopathy and ascites, and highest MELD scores. MASLD/AIH patients had higher transplantation incidence (adjusted subdistribution hazard ratio [aSHR] 1.64, 95% CI 1.44-1.85; p < .001) and lower waitlist removal risk (aSHR .30, 95% CI .20-.44; p < .001) compared to MASLD alone. One-year post-LT survival favoured MASLD compared to AIH (patient: 92% vs. 91%, p < .001; graft: 89% vs. 88%, p < .001) and MASLD/AIH (patient: 92% vs. 90%, p = .008; graft: 89% vs. 88%, p = .023). Recipients with MASLD/AIH showed no significant difference in survival at 10-year post-LT compared to MASLD (patient: 63% vs. 61%, p = .68; graft 60% vs. 59%, p = .83) and AIH (patient: 63% vs. 70%, p = .07; graft: 60% vs. 64%, p = .42). CONCLUSIONS: Our study showed that MASLD/AIH patients demonstrate higher LT incidence and lower dropout rates. Long-term post-LT outcomes did not significantly differ between groups. Further prospective multicenter studies are needed to validate these findings.

ECMO in severe hypoxemia post liver transplant for hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) poses a significant challenge in liver transplant patients, affecting between 10% and 30% of candidates. Historically, HPS was considered a contraindication for liver transplantation due to its association with high mortality rates. However, recent studies have shown improvements in pulmonary function post-transplant, leading to the inclusion of these patients as candidates. Despite this progress, approximately one-fifth of liver transplant recipients develop severe postoperative hypoxia, further complicating their clinical course and contributing to increased mortality. The management of post-transplant HPS involves various strategies, including extracorporeal membrane oxygenation (ECMO), although its use remains infrequently reported. Theoretical models suggest that oxygenation typically improves within 10 days post-transplant, while resolution of HPS may take 6-12 months, making ECMO an attractive possibility as a bridge to recovery in this population. We present a case were ECMO was used in this context.

The predictive role of autonomic neuropathy in pre- and post-liver transplantation outcomes: a systematic review and meta-analysis.

Background: Autonomic neuropathy (AN) in cirrhotic patients has been linked to a higher risk of cirrhosis-related complications and worse outcomes before, during or after liver transplantation (LT). However, only a few studies exist with inconsistent results. Methods: We searched for all articles published until September 2023 that described a diagnosis of AN based on cardiovascular autonomic reflex tests (CARTs), assessment of the rate-corrected QT interval (QTc), heart rate variability (HRV), and baroreflex sensitivity (BRS) tests, in order to evaluate the predictive role of AN in cirrhosis and/or peri-/post-LT prognosis. Results: Twenty-five studies were included: 5, 12, 9, and 1 study, respectively, assessed the predictive role of CARTs, prolonged QTc, HRV indices, and BRS in cirrhosis or peri-/post-LT prognosis. In CARTs-based analysis, the pre-LT pooled mortality rate was significantly higher in cirrhotics with AN compared to those without AN (20% vs. 6%; P=0.01). However, no difference was found between patients with and without pre-LT prolonged QTc in the pre-LT pooled mortality rates (41% vs. 18%; P=0.08), pooled peri-transplant risk of major complications (29% vs. 17%; P=0.08) or post-LT pooled mortality rates (15% vs. 12%; P=0.36). In HRV-based analysis, the standard deviation of normal-to-normal intervals was significantly lower in non-survivors, compared to survivors with cirrhosis: standardized mean difference -2.59, 95% confidence interval -4.75 to -0.43; P=0.04. Conclusions: The presence of CARTs- and HRV-based AN was a good predictor of mortality in the pre-LT setting. Preoperative prolonged QTc did not seem to be associated with the outcome before or after LT.

Liver function maximum capacity test during normothermic regional perfusion predicts graft function after transplantation.

Purpose: In an effort to reduce waitlist mortality, extended criteria donor organs, including those from donation after circulatory death (DCD), are being used with increasing frequency. These donors carry an increased risk for postoperative complications, and balancing donor-recipient risks is currently based on generalized nomograms. Abdominal normothermic regional perfusion (aNRP) enables individual evaluation of DCD organs, but a gold standard to determine suitability for transplantation is lacking. This study aimed to incorporate individualized and predictive measurements of the liver maximum capacity (LiMAx) test to objectively grade liver function during aNRP and prevent post-op complications. Methods: aNRP was performed to salvage 18 DCD liver grafts, otherwise discarded. Continuous variables were presented as the median with the interquartile range. Results: The liver function maximum capacity (LiMAx) test was successfully performed within the aNRP circuit in 17 aNRPs (94%). Donor livers with good lactate clearance during aNRP demonstrated significantly higher LiMAx scores (396 (301-451) µg/kg/h versus those who did not 105 (70-158) µg/kg/h; P = 0.006). This was also true for manifesting stress hyperglycemia > 20 mmol/l (P = 0.032). LiMAx score correlated with alanine aminotransferase (ALT; R = - 0.755) and aspartate transaminase (AST; R = - 0.800) levels during perfusion and distinguished livers that were selected for transplantation (397 (346-453) µg/kg/h) from those who were discarded (155 (87-206) µg/kg/h; P < 0.001). Twelve livers were accepted for transplantation, blinded for LiMAx results, and all had LiMAx scores of > 241 µg/kg/h. Postoperatively, LiMAx during aNRP displayed correlation with 24-h lactate levels. Conclusions: This study shows for the first time the feasibility to assess liver function during aNRP in individual donor livers. LiMAx presents an objective tool to predict donor liver function and risk of complications in the recipient, thus enabling individualized matching of donor livers for an individual recipient. The LiMAx test may present a valuable test for the prediction of donor liver function, preventing post-transplant complication, and personalizing the selection of donor livers for individual recipients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00371-7.

Identification of HIV infection in two solid organ recipients three years after transplantation / Identificación de infección por el virus de la inmunodeficiencia humana en dos receptores de órgano sólido tres años después del trasplante

Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.

El examen de rutina de los donantes de órganos para detectar la infección por el virus de la inmunodeficiencia humana (HIV) ha hecho que la transmisión del virus mediante el trasplante de órganos sea poco común. Sin embargo, a pesar de las pruebas de detección de rutina, la transmisión del HIV continúa siendo un riesgo del trasplante de órganos ya que, a diferencia de los tejidos, los órganos sólidos no se pueden procesar, desinfectar, ni modificar para inactivar patógenos infecciosos. A continuación, se describe un caso de posible transmisión de HIV por trasplante de órganos de un donante previamente seronegativo a dos de sus receptores.

Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis.

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.

Effects of donors' and recipients' preoperative serum sodium on the prognosis of liver transplantation.

Dysnatremia is common in donors and recipients of liver transplantation (LT). However, the influence of dysnatremia on LT prognosis remains controversial. This study aimed to investigate effects of donors' and recipients' serum sodium on LT prognosis. We retrospectively reviewed 248 recipients who underwent orthotopic LT at our center between January 2016 and December 2018. Donors and recipients perioperative and 3-year postoperative clinical data were included. Delta serum sodium was defined as the donors' serum sodium minus the paired recipients' serum sodium. Donors with serum sodium > 145 mmol/L had significantly higher preoperative blood urea nitrogen (BUN) (P < 0.01) and creatinine (Cr) (P < 0.01) than others. Preoperative total bilirubin (TBIL) (P < 0.01), direct bilirubin (DBIL) (P < 0.01), BUN (P < 0.01), Cr (P < 0.01) were significantly higher in the hyponatremia group of recipients than the other groups, but both of donors' and recipients' serum sodium had no effect on the LT prognosis. In the delta serum sodium < 0 mmol/L group, TBIL (P < 0.01) and DBIL (P < 0.01) were significantly higher in postoperative 1 week than the other groups, but delta serum sodium had no effect on the postoperative survival rates. Dysnatremia in donors and recipients of LT have no effect on postoperative survival rates, hepatic and renal function, but recipients with higher serum sodium than donors have significantly higher TBIL and DBIL at 1 week postoperatively.