Liver Transplant Recipients Research Articles

S425 Colorectal Cancer Screening in Liver Transplant Recipients: A Single Center, Retrospective Analysis

S425 Colorectal Cancer Screening in Liver Transplant Recipients: A Single Center, Retrospective Analysis

S1684 Outcomes in Admissions for Acute Cholangitis in Liver Transplant Recipients: A Nationwide Perspective

S1684 Outcomes in Admissions for Acute Cholangitis in Liver Transplant Recipients: A Nationwide Perspective

S1916 Prevalence of Different Malignancies Among Liver Transplant Recipients: A Nationwide Study

S1916 Prevalence of Different Malignancies Among Liver Transplant Recipients: A Nationwide Study

Disturbed sleep after lung transplantation is associated with worse patient-reported outcomes and chronic lung allograft dysfunction

Many lung transplant recipients fail to derive the expected improvements in HRQL and survival. Sleep may represent an important, albeit rarely examined, factor associated with lung transplant outcomes.Within a larger cohort study, 141 lung transplant recipients completed the Medical Outcomes Study (MOS) Sleep Problems Index Revised (SPI) scale along with a broader survey of patient-reported outcome (PRO) measures and frailty assessment. From the SPI we also derived an insomnia-specific subscale. Potential perioperative risk factors for disturbed sleep were derived from medical records. We investigated associations between perioperative predictors on SPI and Insomnia and associations between SPI and Insomnia on PROs and frailty by linear regressions, adjusting for age, sex, and lung function. We evaluated the associations between SPI and Insomnia on time to chronic lung allograft dysfunction (CLAD) and death using Cox models, adjusting for age, sex, and transplant indication.Post-transplant hospital length of stay >30 days was associated with worse sleep by SPI and insomnia (SPI: p=0.01; Insomnia p=0.02). Worse sleep by SPI and insomnia was associated with worse depression, cognitive function, HRQL, physical disability, health utilities, and Fried Frailty Phenotype frailty (all p<0.01). Those in the worst quartile of SPI and insomnia exhibited increased risk of CLAD (HR 2.18; 95%CI: 1.22—3.89; p=0.01 for SPI and HR 1.96; 95%CI 1.09—3.53; p=0.03 for insomnia). Worsening in SPI but not insomnia was also associated with mortality (HR: 1.29; 95%CI: 1.05—1.58; p=0.01).Poor sleep after lung transplant appears associated with patient-reported outcomes, frailty, CLAD, and death. Clarifying the nature of this association may have important screening implications.

Pembrolizumab in combination with lenvatinib in participants with hepatocellular carcinoma (HCC) before liver transplant as neoadjuvant therapY-PLENTY pilot study.

The high recurrent rate after liver transplantation (LT) remains a clinical challenge, especially for those exceeding the Milan criteria (MC) and with high RETREAT scores. Therefore, the authors aim to investigate whether neoadjuvant systemic therapy allows safely administered and effectively reduces post-LT recurrence for those patients. In this prospective, randomized, open-label, pilot study, patients with HCC exceeding the MC were randomly assigned to PLENTY or control group before LT. The primary endpoint of the study was the recurrence-free survival after LT. Twenty-two patients were enrolled and randomly assigned: 11 to the PLENYT group and 11 to the control group. The 30-month tumor-specific RFS was 37.5% in the PLENTY group and 12.5% in the control group. The 12-month tumor-specific RFS after LT was significantly improved in the PLENTY group (87.5%) compared to the control group (37.5%) (P=0·0022). The objective response rate in the PLENTY group was 30 and 60% when determined by RECIST 1.1 and mRECIST, respectively. Six patients (60%) had significant tumor necrosis, including three (30%) who had complete tumor necrosis at histopathology. No acute allograft rejection after LT occurred in the PLENTY and Control group. Neoadjuvant pembrolizumab plus lenvatinib before LT appears to be safe and feasible, associated with significantly better RFS for patients exceeding the MC. Despite the limitations of small sample size, this is the first RCT to evaluate neoadjuvant PD-1 blockade combined with tyrosine kinase inhibitors in LT recipients, the results of this study will inform future research.

Geographic disparities in primary care physicians: Local impact on long-term outcomes in adult liver transplant recipients

BackgroundGeographic inequities are known to affect access to liver transplant (LT); however, the impact of these disparities postoperatively remains unknown. We focus on primary care physicians (PCPs), as frequent managers of long-term LT recipient care. MethodsClinical data on adults undergoing liver-only transplant 2010–2021 were obtained from the Organ Procurement and Transplantation Network and linked to zip code-based PCP density and social vulnerability index (SVI) data to quantify the impact of PCP density on graft and overall survival. Results64,593 patients were divided into quintiles by PCP density. Compared to patients in the lowest PCP quintile, patients in the 3rd, 4th, and 5th quintiles had 6%–8% lower mortality risk (HR3rd ​= ​0.94, HR4th ​= ​0.92, HR5th ​= ​0.94, p for trend ​= ​0.002). PCP density remained significant after accounting for SVI and local surgeon and gastroenterologist availability (p ​= ​0.002). ConclusionsIncreased PCP availability is associated with improved survival, emphasizing the importance of establishing longitudinal care.

Bilateral Native Renal Vein Thrombosis in a Liver and Kidney Transplant Recipient

Bilateral Native Renal Vein Thrombosis in a Liver and Kidney Transplant Recipient

A blood-based PT-LIFE (Pediatric Liver Transplantation-LIver Fibrosis Evaluation) biomarker panel for noninvasive evaluation of pediatric liver fibrosis after liver transplantation: A prospective derivation and validation study

Allograft fibrosis is increasingly detected in graft biopsies as the postoperative period extends, potentially emerging as a pivotal determinant of long-term graft function and graft survival among pediatric recipients. Currently, there is a paucity of noninvasive diagnostic tools capable of identifying allograft fibrosis in pediatric recipients of liver transplants. This study involved 507 pediatric liver transplant patients and developed a novel blood-based diagnostic assay, Pediatric Liver Transplantation-Liver Fibrosis Evaluation (PT-LIFE), to noninvasively distinguish allograft fibrosis using blood samples, clinical data, and biopsy outcomes. The PT-LIFE assay was derived from a matrix of 23 variables and validated in 2 independent cohorts. It integrates 3 biomarkers (LECT2, YKL-40, FBLN3) with an area under the receiver operating characteristic curve of 0.91. In the pooled analysis, a PT-LIFE score lower than 0.12 identified liver allograft fibrosis semiquantitative scores 0 to 2 with a sensitivity of 91.9%, whereas scores above 0.29 indicated liver allograft fibrosis semiquantitative scores 3 to 6, with a specificity of 88.4%. The PT-LIFE assay presents as a promising noninvasive diagnostic tool for the detection of allograft fibrosis in pediatric liver transplant recipients.

Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience.

The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8kPa ± 3.2) compared to patients with F0 fibrosis (5.2kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1kPa ± 1.5) (p = 0.041), on ANOVA. Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.

Detection of Early Postoperative Active Bleeding After Liver Transplantation in Pediatric Patients by 384-Slice Computed Tomography Angiography.

Liver transplant is a complex procedure often complicated by postoperative bleeding events. Early detection of active bleeding is crucial for effective intervention. In this study, we evaluated the efficacy of 384-slice computed tomography angiography in identifying early postoperative active bleeding events after liver transplant. We retrospectively analyzed 53 liver transplant recipients from February 1, 2022, to December 26, 2023. All patients underwent 384-slice computed tomography angiography, capturing arterial, venous, and delayed phases. Results showed that 34.2% of patients experienced bleeding events, with 28.57% of these patients having active bleeding complications. Recurrent bleeding occurred in 3.77% of cases. Computed tomography angiography demonstrated 100% sensitivity, specificity, and positive predictive value in detecting bleeding. Bleeding primarily originated from the perihepatic region and was predominantly arterial. Our findings underscore the value of 384-slice computed tomography angiography in early detection and localization of postoperative bleeding, which enhances patient management and outcomes. Integrating this advanced imaging tool into routine postoperative care can significantly improve intervention accuracy and patient recovery.

LTSI Consensus Guidelines: Preoperative Cardiac Evaluation in Adult Liver Transplant Recipients

LTSI Consensus Guidelines: Preoperative Cardiac Evaluation in Adult Liver Transplant Recipients

S1816 Impact of Frailty on MASLD Liver Transplant Recipients: An Analysis of the National Readmission Database

S1816 Impact of Frailty on MASLD Liver Transplant Recipients: An Analysis of the National Readmission Database

Evaluating the yield of digital single operator cholangioscopy in posttransplant biliary strictures after unsuccessful guidewire placement with ERCP.

Strictures are the most common biliary complication after liver transplantation, and endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard in its management. Failure to cross the biliary anastomosis requires a repeated attempt with ERCP, referral for percutaneous transhepatic cholangiography (PTC) or surgery. We present our experience with the digital single operator cholangioscope (D-SOC) in achieving guidewire access in a liver transplant cohort with difficult biliary strictures who have failed conventional ERCP methods. This was a retrospective study involving two adult liver transplant centers servicing the two most populated states in Australia. Deceased-donor liver transplant recipients undergoing D-SOC for biliary strictures who have failed conventional methods to achieve biliary access were included. Between July 2017 to April 2022, eighteen patients underwent D-SOC after failing to achieve guidewire placement through standard ERCP techniques. Thirteen out of eighteen (72%) had successful guidewire placement with index D-SOC. Five of eighteen patients (28%) had unsuccessful guidewire placement with D-SOC. In two of these patients, use of D-SOC informed further endoscopic management, with one avoiding PTC and the other avoiding surgery. Two of the five patients required PTC and one patient was left unstented. Three patients developed post D-SOC cholangitis. D-SOC is effective at achieving guidewire access in post-liver transplant patients who fail conventional ERCP techniques and should be considered in the treatment algorithm as a step before PTC and surgery.

Less is more: The use of a single biodegradable stenting to treat biliary anastomotic strictures in pediatric liver transplantation.

To report our experience of using biodegradable biliary stents for anastomotic biliary strictures in pediatric liver transplant patients. Analysis of a retrospective data collection from January 2014 to January 2023, including all pediatric liver transplant recipients in our center treated for anastomotic biliary strictures with biodegradable biliary stents (BBS). In phase 1 (2014-2019), there was an initial percutaneous transhepatic cholangiography (PTC) with anastomotic dilatation followed two weeks after by a second PTC with BBS insertion. In phase 2 (2019-2023), the BDS were placed shortly after anastomotic biliary strictures dilatation, requiring only one PTC. All patients were followed up with routine tests and ultrasound. Forty-six anastomotic biliary strictures were diagnosed in 43 pediatric liver transplant recipients with a median of 6.7 months post-liver transplantation (0.1-246.8 months). Eight out of 46 anastomotic biliary strictures (17.4%) treated with biodegradable biliary stents relapsed (median recurrence time: 6.5 months; 1.6-17.0 months). Four resolved with further BBS placement; only four needed surgical revision (8.7%) after a median follow-up time of 43.9 months (0.3-106.3). There were no differences in anastomotic biliary strictures recurrence rate, time between stent placement and recurrence, or the presence of cholangitis based on whether the BBS was deployed in one or two steps. Patients with end-to-end anastomosis had a higher anastomotic biliary strictures recurrence (or 10.8; 1.4-81.3, p=0.008) than those with bilioenteric anastomosis. The use of biodegradable stents stents could be good option for treating anastomotic biliary strictures in pediatric liver transplant patients, with our series showing a success rate of over 90% and an average follow-up of 43.9 months.

Thrombotic microangiopathy as a rare complication after lung transplantation

Thrombotic microangiopathy (TMA) is defined by the typical triad of severe thrombocytopenia, hemolytic anemia and endorgan dysfunction and can be characterized by the pathophysiology of ischemia-inducing microthrombi in arterioles and capillaries possibly leading to severe organ dysfunction up to acutely life-threatening endorgan damage. In terms of etiology, management, therapy and prognosis, the following manifestations are distinguished: thrombotic thrombocytopenic purpura (TTP), shigatoxin-induced hemolytic-uremic syndrome (STEC-HUS), secondary comorbidity-related TMA and atypical hemolytic-uremic syndrome (aHUS). We present the case of a 49 year old lung transplant recipient developing aHUS. The complexity of the underlying pathomechanisms of TMA, the complicated differentiation of each TMA manifestation and the complex management of aHUS in the post-transplant setting illustrate the uniqueness of this patient case.

Impact of tacrolimus vs cyclosporine on chronic lung allograft dysfunction incidence and allograft survival in the International Society of Heart and Lung Transplantation registry

PurposeThe ScanCLAD study reported a lower incidence of CLAD with the use of once-daily tacrolimus vs. twice-daily cyclosporine. Using the ISHLT Thoracic Organ Transplant (TTX) Registry data, we evaluated the hypothesis that tacrolimus is superior to cyclosporine in real world clinical practice. MethodsThis study is a retrospective cohort study of adult lung transplant recipients in the ISHLT Registry from January 1, 2000 through June 30, 2018 with known CLAD status. The primary exposure variable was patients’ maintenance calcineurin inhibitor (CNI) regimen captured at post-transplant discharge. The primary outcome variables were time to CLAD development (with death/retransplantation analyzed as a competing risk) and allograft survival (i.e., time to death/retransplant). ResultsOf the 57,403 adult lung transplant recipients in the registry, 22,222 had both CNI and CLAD data available. Of these, 19,698 (88.6%) received tacrolimus immediate release (IR), 2,477 (11.2%) received cyclosporine, and 47 (0.2%) received tacrolimus extended release (XR) for maintenance CNI. Receiving cyclosporine for maintenance immunosuppression (vs. tacrolimus IR) was associated with an increased risk of developing CLAD (HR 1.16, 95% CI 1.08-1.23, p<0.001) and with an increased overall risk for death/retransplant (HR 1.16, 95% CI 1.09-1.23, p<0.001). Receiving tacrolimus XR vs. tacrolimus IR was not associated with differences in long-term post-transplant outcomes, although these analyses were limited by a small sample size. ConclusionsPatients receiving cyclosporine vs. tacrolimus IR for maintenance calcineurin inhibition had an increased risk of CLAD and decreased overall allograft survival in the ISHLT TTX registry.

Intercostal Nerve Cryoablation in Lung Transplantation: A Single-Center, Propensity-Matched Analysis

ObjectiveAchieving adequate pain control after lung transplantation is an essential milestone in a patient’s recovery. We compared postoperative opioid use, clinical outcomes, and respiratory function in lung transplant recipients treated with intercostal nerve cryoablation (INC) vs standard pain management. MethodsWe reviewed all adult lung transplants performed at our center between January 2016 and December 2022. We excluded cases performed through median sternotomy , patients with prior thoracotomies, multiorgan transplants, and redo transplants. We performed a propensity matched analysis, comparing patients who received INC versus standard pain management The primary outcome was cumulative postoperative opioid use in morphine milligram equivalents (MME) by POD 14. Secondary outcomes included opioid use on POD5 and POD10, perioperative outcomes, 1-year survival and longitudinal measurement of respiratory function. ResultsPropensity matching resulted in 85 patients in each group. Compared to standard pain management, the INC group had a lower cumulative opioid use by POD 14 (509 vs 864 MME, p=0.032). In addition, the INC group had a lower opioid use at POD5, POD10, POD14, no difference in perioperative outcomes, and similar 1-year survival. The INC group had better respiratory function at 6 and 12-months posttransplant compared to the standard pain management group. ConclusionsIn our single center analysis, INC was associated with lower opioid use and improved respiratory function after lung transplant. This report adds to the growing literature supporting the use of INC in multimodal pain management strategies and enhanced recovery protocols in lung transplant.

Distinct Non-Human Leukocyte Antigen Antibody Signatures Correlate with Endothelial Crossmatch Status in Lung and Renal Transplant Recipients

Non-HLA antibodies against heterogeneous targets on endothelial cells have been associated with allograft injuries. The endothelial cell crossmatch (ECXM) is used in the detection of non-HLA antibodies but remains non-discriminatory for specific antibody identification. The primary objective of this study was to delineate the specific non-HLA antibody signatures associated with ECXM positivity and to determine the correlation of ECXM status and non-HLA antibody signatures on allograft health. Serum specimens from 25 lung transplant recipients (LTRs) and 13 renal transplant recipients (RTRs) were collected as part of clinical evaluation, and testing for angiotensin II receptor type 1 (AT1R) and donor-specific MHC class I chain-related gene A (MICA) antibodies and ECXM was performed. Remnant sera were tested for non-HLA antibodies using the LABScreen™ Autoantibody (LSAUT) Group 1, 2, and 3 kits (One Lambda, Inc., Los Angeles, CA, USA). In both cohorts, the concordance of AT1R and MICA together or individually with ECXM+ status was poor (&lt;0.7), suggesting the presence of other unaccounted antibodies. Autoantibody profiling revealed three distinct clusters targeting fibrotic products, cytoskeletal proteins, and cell signaling molecules. A comparative analysis of ECXM+ and ECXM− specimens identified nine and five differentially expressed antibodies in the LTR and RTR cohorts, respectively. Employing machine learning techniques (variable importance, feature selection, ROC-AUC), we derived a five-antibody panel (TNFα, collagen V, CXCL11, GDNF, GAPDH) and a two-antibody panel (TNFα, CXCL9) that effectively discriminated between ECXM+ and ECXM− status in the LTR and RTR cohorts, respectively. Distinct antibody signatures were identified in LTR and RTR cohorts that correlated with ECXM+ status and were associated with allograft dysfunction.

Machine learning for post-liver transplant survival: Bridging the gap for long-term outcomes through temporal variation features

BackgroundThe long-term survival of liver transplant (LT) recipients is essential for optimizing organ allocation and estimating mortality outcomes. While models like the Model-for-End-Stage-Liver-Disease (MELD) predict 90-day mortality on the waiting list, they do not predict post-LT survival accurately. There is a need for predictive models that can forecast post-LT survival beyond the immediate period after transplantation. MethodThis study introduces new temporal variation features for predicting post-LT survival during the waiting list period. Cox Proportional-Hazards regression (CoxPH), Random Survival Forest (RSF), and Extreme Gradient Boosting (XGB) models are utilized, along with patient demographics and waiting list duration. Data from 716 LT patients from the University of Minnesota CTSI (2011–2021) are used to develop, evaluate, and compare post-LT survival prediction models. ResultsThe temporal variation features, particularly when combined with the RSF model, proved most effective in predicting post-LT survival, with a C-index of 0.71 and an IBS of 0.151. This outperformed the predictive capability of the most recent MELD score, which had a C-index of <0.51 in the same cohort. ConclusionsIncorporating temporal variation features with the RSF model enhances long-term post-LT survival predictions. These insights can assist clinicians and patients in making more informed decisions about organ allocation and understanding the utility of LT, ultimately leading to improved patient outcomes.

Efficacy and safety of a preventive strategy against tuberculosis in liver transplantation recipients including the treatment of latent infection with moxifloxacin.

Preventive management of tuberculosis in liver transplantation (LT) is challenging due to difficulties in detecting and treating latent tuberculosis infection (LTBI). The aim of this study was to analyze the safety and efficacy of a screening strategy for LTBI with the inclusion of moxifloxacin as treatment. We performed a retrospective single-center study of all LTs performed between 2016 and 2019 with a minimum 4-year follow-up and a standardized protocol for the evaluation of LTBI. Pretransplant LTBI screening was performed in 191/218 (87.6%) patients, and LTBI was diagnosed in 27.2% of them. Treatment for LTBI was administered to 71.2% of the patients and included moxifloxacin in 75.6% of the cases. After a median follow-up of 1628 days, no cases of active tuberculosis occurred among moxifloxacin-treated patients. The incidence of Clostridioides difficile (0.46vs. 0.38 episodes/1000 transplant-days; p = .8) and multidrug-resistant gram-negative bacilli infection (0vs. 0.7 episodes per 1000 transplant-days; p = .08) were not significantly higher in comparison to patients who did not receive moxifloxacin. A preventive strategy based on systematic LTBI screening and moxifloxacin treatment before LT in positive cases appears safe and effective in preventing the development of tuberculosis in LT recipients. However, our findings are limited by a small sample size; thus, larger studies are required to validate our observations.