Pediatric Liver Transplant Patients Research Articles

P-2278. CMV Viremia and Disease in Pediatric Liver Transplant Patients: a Multi-national Systematic Review and Meta-analysis

Abstract Background Cytomegalovirus (CMV) viremia (Defined as a single detectable CMV RNA PCR) and disease (defined as CMV viremia with compatible systemic and/or localized signs and symptoms) remain a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient. This systemic review aims at pooling data from the leading pediatric transplant institutions globally to identify the overall incidence of and risk factors associated with CMV viremia and/or disease in pediatric liver transplant recipients. PRISMA flow diagram Methods A systemic review of Pubmed and OVID databases was conducted since the inception to 01 April 2024. 24 articles were included from the USA, UK, South Africa, India, Japan, Finland, Canada, Turkey, Mexico, Thailand, Greece, Israel and Australia. A total of 1964 liver transplants were included. Median age was 50 months with 47.8% males. Data related to demographics, incidence, donor and recipient CMV serological classification (Donor (D) and Recipient (R)) and risk factors for CMV viremia/disease were extracted from the articles and subsequently analysed. This review was registered in Prospero: CRD42023477476 Results The Incidence of CMV viremia and disease in pediatric liver transplant patients in this review were 34% and 8.4% respectively, with statistically significant higher risk in the CMV D+/R+ category compared to other D/R serologic groups (P value < 0.05). , Additional risk factors identified for CMV viremia/disease included younger age, biliary atresia, high steroid doses, and rejection attacks. Conclusion This meta-analysis highlights that CMV viremia and disease post-liver transplantation are significant health concerns in pediatric populations. Identifying high risk populations for targeted CMV monitoring and potentially preemptive therapy to mitigate CMV-associated morbidity and mortality is a critical cornerstone of pediatric transplant medicine. Further studies are warranted to explore additional risk factors and to refine prevention and treatment strategies for CMV in pediatric transplant recipients. Disclosures All Authors: No reported disclosures

Effect of Age at Liver Transplant on Anxiety, Depression, and Quality of Life Among Adolescents.

Introduction: Life expectancy for pediatric liver transplant patients has increased over the past decade. Different stages of the transplant process can impact patients' quality of life (QOL) and create psychological and physical stressors. This study explored whether age at transplant affected adolescents' feelings of anxiety, depression, and QOL. Design: In this cross-sectional quantitative study, data were collected on 22 adolescent patients aged 13-18 who received a transplant at least 12 months before enrollment. This cohort was divided into 2 groups based on their age at transplant: Group 1 (0-5 years) and Group 2 (6-18 years). To assess transplant-related anxiety, depression, and QOL, participants completed 3 surveys: the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the Pediatric Quality of Life Inventory™ Transplant Module (PedsQL TM). Results: Group 1 experienced less anxiety and fewer problems based on GAD-7 scores but reported stronger feelings of depression based on PHQ-9 scores. Based on the PedsQL TM scale, Group 1 had higher mean scores compared to Group 2 across all components (mean difference range: 7.2- 27.3; Cohen's d range: 0.27 - 1.13). The largest difference between the 2 groups was observed on the PedsQL TM scale's How I Look (Group 1 mean 81.1 vs. Group 2 mean 53.8; Cohen's d: 1.13; P = 0.015), Conclusion: In this cohort, age at transplant affected adolescents' feelings of anxiety, depression, and QOL. Awareness of these findings can help clinicians screen for and address mental health issues.

Study of related factors to vascular complications after pediatric liver transplantation

Objective: To explore the related factors of vascular complications after liver transplantation in children. Methods: This is a retrospective case series research. The clinical data of 89 pediatric liver transplant patients admitted to the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2016 to March 2024 were collected retrospectively. This study included 44 males and 45 females,aged from 4 months to 17 years. The ratio of graft to recipient weight was 0.6% to 7.7%. The primary diseases included 48 cases of biliary atresia and 41 cases of non-biliary atresia. The Wilcoxon rank sum test, χ2 test, and Fisher's exact probability method were used for data analysis. Multivariate Logistic regression was used to analyze the related factors of vascular complications. Results: All 89 children with liver transplantation completed surgery successfully. There were 8 cases of arterial complications after surgery, including 6 cases of hepatic artery thrombosis and 2 cases of hepatic artery stenosis. There were 16 cases of portal vein complications after surgery, including 9 cases of portal vein stenosis and 7 cases of portal vein thrombosis. The results of univariate analysis showed that the age of the recipient ≤1 year was the relevant factor for hepatic arterial complications(χ2=4.772,P=0.029). The age of the recipient ≤1 year, the age of the donor, the hepatic phase, and the time of cold ischemia were the relevant factors for the occurrence of portal vein complications(χ2=7.270,Z=388.500,Z=838.000, Z=894.500;all P<0.05). The results of multivariate analysis showed that age(≤1 year vs. >1 year) and duration of cold ischemia(every additional 1 hour) were independent related factors for portal vein complications after liver transplantation in children(both P<0.05). Conclusion: Children aged ≤1 year and with prolonged cold ischemia are more likely to develop portal vein complications after liver transplantation.

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.

Key Aspects of Pediatric Liver Transplant Patient Visits to the Pediatric Emergency Department.

Patients with liver transplant can present to a pediatric emergency department with short- and long-term complications of transplant. Here, we described clinical features of pediatric liver transplant patients admitted to the pediatric emergency department and identified risk factors that may lead to pediatric intensive care unit admission. We retrospectively evaluated pediatric liver transplant patients admitted posttransplant to Baskent University Hospital's pediatric emergency department in 2023. We noted symptoms, laboratory tests, hospitalization status, and final diagnoses. We compared clinical and laboratory features of patients admitted or not admitted to the intensive care unit. In 2023, 108 presentations of 33 liver transplant patients presented to our pediatric emergency department: 46.3% were girls, mean age was 7.79 ± 4.40 years, and median posttransplant day at time of emergency department visit was 622 days. Common symptoms were vomiting (48%), fever (46%), and rhinorrhea and cough (34%). Forty-nine visits (45.4%) resulted in hospitalization; 5 visits (4.6%) resulted in PICU admission, with 2 mortalities (1.8%). Final diagnoses included acute gastroenteritis and upper respiratory tract infections (23 patients) and lower respiratory tract infections (13 patients). Seven patients had cholangitis, 6 had intra-abdominal infection, and 5 had sepsis. Seizures and sepsis were significantly correlated with intensive care unit admission (P <.001). Patients admitted to the intensive care unit had significantly shorter time posttransplant versus other patients (518 ± 324 vs 1498 ± 1658 days; P < .001). Half of patients who presented to the emergency department required hospitalization mainly for observation and supportive treatment, with a small number requiring intensive care unit admission. Nevertheless, physicians caring for liver transplant patients should be aware of serious complications and monitor patients closely, especially early posttransplant when intensive immunosuppressive treatment regimens are used.

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.

Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review.

Immunosuppressive medications play a crucial role in determining both organ and patient survival following liver transplantation (LT). Typically, immunosuppressive protocols for pediatric LT patients rely on calcineurin inhibitors (CNIs). While inhibitors of mammalian target of rapamycin (mTOR) have demonstrated beneficial outcomes in adult recipients of liver allografts, such as improved renal function post-LT, their application in pediatric liver transplant recipients is a subject of debate due to uncertain efficacy and potential adverse effects. This review evaluates the potential roles of mTOR inhibitors in the context of pediatric LT patients. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for conduct and reporting. Databases until 31 August 2023 were searched using specific terms and keywords. All clinical studies focusing on mTOR inhibitors in pediatric LT were included. Out of 888 identified articles, 30 studies, involving 386 children who had undergone liver transplantation and received mTOR-inhibitor-based immunosuppressive regimens, met the inclusion criteria. The beneficial impacts of switching from a CNI to an mTOR inhibitor or adding an mTOR inhibitor to CNI-reduced immunosuppression in LT pediatric patients with impaired kidney function are controversial, and high-powered clinical studies are need. It appears that enhancing immunosuppression by adding an mTOR inhibitor to CNI is helpful for pediatric LT recipients who are experiencing refractory acute rejection or chronic rejection. mTOR-inhibitor-containing regimens failed to reduce the occurrence of post-transplant lymphoproliferative disorders (PTLD) among children with LT that may be due to concomitant high CNI concentration among studied patients. The effectiveness of mTOR inhibitors in treating PTLD remains uncertain; however, in patients with PTLD who are at high risk of rejection, mTOR inhibitors may be administered. Conversion to or the addition of mTOR inhibitors to maintenance immunosuppression seems to be suitable for pediatric patients who received a transplant due to hepatic malignancies such as hepatoblastoma or hepatocellular carcinoma or for those with post-transplant primary or recurrent malignancies. Switching to an mTOR inhibitor may improve some CNI-related adverse effects such as gingival hyperplasia, neurotoxicity, nephropathy, hypertrophic cardiomyopathy, or thrombotic microangiopathy. Although the exact role of mTOR inhibitors among pediatric patients who have received a liver transplant needs further study, two algorithms are presented in this review to guide conversion from CNIs to mTOR inhibitors or the addition of mTOR inhibitor to a CNI-minimization immunosuppressive regimen for pediatric patients who may benefit from this class of drugs. This review mainly consisted of retrospective studies with inadequate sample sizes and lacked a control group, which represents the main limitation of this study.

P.364: Increased psychosocial risk factors in pediatric liver transplant patients transplanted for fulminant liver failure.

P.364: Increased psychosocial risk factors in pediatric liver transplant patients transplanted for fulminant liver failure.

204.4: Major aspects of pediatric liver transplant patient visits to the pediatric emergency department during post-operative follow-up period.

204.4: Major aspects of pediatric liver transplant patient visits to the pediatric emergency department during post-operative follow-up period.

Perioperative Fluid Management in Paediatric Liver Transplantation: A Systematic Review.

Perioperative fluid management remains a challenging aspect of paediatric liver transplantation (LT) because of the risk of postoperative complications and haemodynamic instability. Limited research has specifically investigated the impact of fluid management and transfusion on mortality and morbidity in pediatric LT patients. This systematic review summarizes the evidence regarding perioperative fluid management and its clinical outcomes in paediatric LT patients. All primary studies published in English evaluating perioperative fluid management in paediatric LT patients were eligible. PubMed, EBSCOHost, Embase, Proquest, and Google Scholar databases were searched from inception to December 19, 2023. Risks of bias were assessed using the Joanna-Briggs Institute checklist. The results were synthesized narratively. Five retrospective cohort studies of good-excellent quality were included in this review. Two studies evaluated intraoperative fluid administration, one study compared postoperative fluid balance (FB) with outcomes, and two studies compared massive versus non-massive transfusion. A higher mortality rate was associated with intravenous lactated ringer's (LR) than with normal saline, but not with massive transfusion (MT). Longer hospital stays were correlated with MT, >20% positive FB in the first 72 hours, and greater total intraoperative blood product administration. Higher intraoperative fluid administration was associated with a greater thrombotic risk. Additionally, intraoperative MT and lR infusion were associated with an increased risk of 30-day graft loss and graft dysfunction, respectively. Fluid management may impact the outcomes of paediatric LT recipients. These findings underscore the need for more studies to explore the best fluid management and evaluation strategies for children undergoing LT.

Sirolimus to treat chronic and steroid-resistant allograft rejection-related fibrosis in pediatric liver transplantation.

This study aimed to report our experience with the use of Sirolimus (SRL) in pediatric liver transplant patients with chronic rejection or steroid-resistant rejection with hepatic fibrosis, focusing on their histological evolution. All pediatric liver transplant recipients who received off-label treatment with SRL for chronic ductopenic rejection or cortico-resistant rejection between July 2003 and July 2022 were included in the study. All nine patients included in the study showed improvement in liver enzymes and cholestasis parameters as soon as 1-month after post-SRL introduction. A decrease in fibrosis stage was observed in 7/9 (77.7%) patients at 36 months. All but one patient experienced an improvement in the Rejection Activity Index and ductopenia at 12 months. A single patient had to discontinue SRL treatment owing to nephrotic proteinuria. In conclusion, SRL may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Development and validation of individualized tacrolimus dosing software for Chinese pediatric liver transplantation patients: a population pharmacokinetic approach.

We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4years old after liver transplantation and to develop individualized tacrolimus dosing software. A total of 663 blood concentrations from 85 patients aged 4.57months to 3.97years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed. A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%). A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation.

Approval of Mycophenolate Mofetil for Prophylaxis of Organ Rejection in Pediatric Recipients of Heart or Liver Transplants: A Regulatory Perspective.

On June 6, 2022, the FDA expanded the indications for mycophenolate mofetil (MMF) to include the prophylaxis of organ rejection in combination with other immunosuppressants in pediatric recipients of allogeneic heart or liver transplants aged 3 months and older. The approved oral dosing regimen for these patients was a starting dose of 600 mg/m2 with titration up to a maximum of 900 mg/m2 twice daily. Data to support efficacy in pediatric patients were derived from established pharmacokinetic (PK) relationships across approved populations, a PK study in pediatric liver transplant recipients, and information from the Scientific Registry of Transplant Recipients database. Information supporting safety was based on comparing mycophenolic acid (MPA) exposure with that in pediatric kidney transplant recipients, the published literature, and post-marketing safety reports. Efficacy in pediatric patients was established based on extrapolation of efficacy from studies in adult liver, adult heart, and pediatric kidney transplant populations, and similarity in MPA exposure between pediatric and adult patients. Review of the data supported an oral dosing regimen for pediatric heart transplant and liver transplant recipients consisting of a starting dose of 600 mg/m2 up to a maximum of 900 mg/m2 b.i.d. A dosage range for MMF is recommended recognizing that the MMF dose may be modified in clinical practice for myriad factors. The dosage recommendations in the labeling for pediatric liver and pediatric heart transplant patients are intended to permit individualized dosing based on clinical assessment of these factors.

Infectious complications in pediatric patients after liver transplantation in the first 3 months at the Fundación Valle del Lili, a Latin American transplant center

IntroductionIn pediatric patients undergoing liver transplantation, infections are one of the primary complications. The etiology varies depending on the time elapsed post-transplant, with early presentations of bacterial and fungal infections, followed by viral and parasitic infections. There is limited literature describing the prevalence of infectious complications in this group of patients in Colombia. ObjectiveTo describe infectious complications in patients undergoing liver transplantation within the first 3 months post-procedure at the Fundación Valle del Lili, Cali, Colombia. MethodsA case series of 165 pediatric liver transplant patients during the period 2011–2017. A descriptive analysis of all entered data was conducted. Survival analysis using the Kaplan-Meier method was performed, with an exploratory analysis comparing patient survival based on the presence of infection, censored for death related to postoperative complications. ResultsThe primary diagnosis at the time of transplantation was biliary atresia in 65% of cases. A total of 215 infectious episodes were recorded in 92 pediatric liver transplants. The most frequent microorganisms were Klebsiella pneumoniae (21%), Cytomegalovirus (CMV) (7%), Pseudomonas aeruginosa (7%), Escherichia coli (6%), and Epstein Barr Virus (EBV) (6%). Three-month patient survival was 92% for infection-related mortality. DiscussionInfectious complications within the first three months post-pediatric liver transplantation were predominantly bacterial in origin. Bacterial and fungal infections manifested earlier, while viral infections appeared later. Infectious complications did not impact the three-month patient survival in this group.

Impact of donor CYP3A5 genotype on pharmacokinetics of tacrolimus in South African paediatric liver transplant patients.

In the paediatric liver transplant programme in Johannesburg, South Africa (SA), tacrolimus is the calcineurin inhibitor of choice, comprising an essential component of the immunosuppression regimen. It is characterised by a narrow therapeutic index and wide interpatient variability, necessitating therapeutic drug monitoring of whole-blood concentrations. Pharmacogenetic research, although not representative of SA population groups, suggests that single-nucleotide polymorphisms within the cytochrome P450 3A5 (CYP3A5) gene contribute to the variability in tacrolimus dosing requirements. The rs776746 polymorphism, CYP3A5*3, results in a splice defect and a non-functional enzyme. Clinically, to reach the same tacrolimus concentration-to-dose ratio (CDR), expressors (CYP3A5*1/*1 and *1/*3) require a higher tacrolimus dose than non-expressors (*3/*3). To compare the pharmacokinetics of tacrolimus in paediatric liver transplant recipients with their donors' CYP3A5 genotypes, considering both donor and recipient characteristics. Blood samples from 46 living liver donors were collected, their genomic DNA was extracted, and their CYP3A5 genotype was established (polymerase chain reaction and restriction fragment length polymorphism analysis, validated by Sanger sequencing). The relationship of donor and recipient characteristics with the mean tacrolimus CDR was analysed using a general linear model. Non- confounding significant variables were included in a multiple regression model. The study showed that all expressor donors genotyped as CYP3A5*1/*1 were of black African self-reported race and ethnicity. During the first 15 days post-transplant, we found that children who received grafts from donor CYP3A5 expressors (CYP3A5*1/*1 and *1/*3) had significantly lower mean tacrolimus CDRs compared with those who received grafts from donor CYP3A5 non-expressors (*3/*3); the recipients of CYP3A5 expressor grafts therefore require higher doses of oral tacrolimus to achieve the same therapeutic target range. In addition, graft-to-recipient weight ratio and the CYP3A5 donor genotypes were independent factors that significantly (p<0.05) affected mean tacrolimus CDRs in recipients. In this study, we showed that all CYP3A5*1 homozygote donors were of black African self-reported race and ethnicity, and tacrolimus CDRs in paediatric living-donor liver transplant recipients were significantly affected by donor graft size and donor CYP3A5 genotypes. Information from this study may inform the development of an Afrocentric tacrolimus precision-medicine algorithm to optimise recipient safety and graft outcomes.

Biliary strictures post pediatric liver transplantation-incidence and risk factors in a single tertiary referral transplant center.

Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence. Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures. Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3-215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses. In our cohort, the presence of two biliary anastomoses and post-transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postope rative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.

Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients. Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency. Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81). Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT)has not been fully elucidated. UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit(ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001)compared to recipients of younger donor (YD)grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1)from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

2725. Bacterial blood stream infections in Pediatric Liver Transplant Patients: Prevalence, Organisms and Risk factors. A Systematic review

Abstract Background Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms. Methods A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206). The PRISMA flow diagram visually summarises the screening process Results A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI. Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries. Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection. Conclusion Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients. Disclosures All Authors: No reported disclosures