Pediatric Liver Transplantation Research Articles

An innocent bystander or a predisposing culprit? Kidney injury following pediatric liver transplantation.

Survival after pediatric liver transplantation has increased dramatically over the years, revealing extra-hepatic complications including impaired kidney function. We conducted a large single-center retrospective study to evaluate kidney outcomes after pediatric liver transplantation. From electronic charts of 121 children who underwent liver transplantation during 2007-2020, we collected pre- and post-transplant data. We investigated the presence of post-transplant permanent kidney injury, including proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR). We excluded children who died, underwent liver-kidney transplantation, or had less than 1year of follow-up. During a median follow-up of 5.1 (interquartile range 2.9-7.3) years, eGFR decreased, mostly in the first year post-transplant. In addition, 41% of the children presented with acute kidney injury. At their last follow-up, 35% showed permanent kidney injury (hypertension 13%, proteinuria 36%, and eGFR < 90mL/min per 1.73m2 7%). Kidney ultrasounds were abnormal for 44% of the children at the last visit, compared to 11% before transplant (p < 0.001). In multivariate analysis, abnormal kidney ultrasound before transplant (odds ratio = 4.53, 95% CI 1.1-18.7) and liver disease with potential risk of primary kidney involvement (odds ratio = 4.77, 95% CI 1.58-14.4) were predictors for hypertension or decreased eGFR at the last follow-up. The high prevalence of kidney injury after pediatric liver transplantation and the pretransplant predictors for kidney injury highlight the importance of a thorough kidney pretransplant evaluation and follow-up.

Optimizing Piperacillin Dosing in Pediatric Liver Transplant Recipients: A Case Series.

Pathophysiological changes post-liver transplantation impact the pharmacokinetics and pharmacodynamics of antibiotics. Piperacillin, often used in combination with tazobactam, is a key antibiotic after transplantation to its broad-spectrum activity, but there is a lack of specific pharmacokinetic data in this population. This study aims to describe the pharmacokinetic parameters and target attainment of piperacillin in pediatric liver transplant recipients. Patients with preserved renal function (estimated glomerular filtration rate > 50 mL/min/1.73 m2) receiving intravenous piperacillin-tazobactam at 112.5 mg/kg every 8 h (100 mg piperacillin/12.5 mg tazobactam), with a rapid infusion (0.5-1 h), were included. Two blood samples per child were collected during the same interval within 48 h of starting therapy. A Bayesian approach was applied to estimate individual pharmacokinetic parameters and perform dosing recommendations against Enterococcus spp., Enterobacterales and Pseudomonas aeruginosa. Eight patients with median age of 8 months were included. Median piperacillin clearance and central volume of distribution for the cohort were 11.11 L/h/70 kg and 9.80 L/70 kg, respectively. Seven patients (87.5%) presented with concentrations below the target of 100% fT > MIC. Simulations suggested that these patients required more frequent dosing and extended duration of infusion to ensure target attainment. One patient (12.5%) had trough concentrations that exceed 16 mg/L and could receive a lower daily dose. This case series highlights the importance of personalized therapy in pediatric liver transplant recipients due to the unpredictable and highly variable piperacillin pharmacokinetics in this population.

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

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). A retrospective cohort study. 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. 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. 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. 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. Paediatric patients contributed electronic health records datasets.

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.

Mapping out a medication adherence promotion system (MAPS): can it reduce graft rejection in pediatric liver transplantation?

Mapping out a medication adherence promotion system (MAPS): can it reduce graft rejection in pediatric liver transplantation?

Postoperative Delirium Screening Characteristics in Pediatric Intestinal, Liver, and Renal Transplant Recipients: Single-Center Retrospective Cohort Study.

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD). Retrospective analysis of a single-center cohort, 2016-2022. Twenty-four-bed PICU in a high-volume transplant center. All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022. We identified 211 pediatric transplant recipients: intestinal ( n = 36), liver ( n = 78), and renal ( n = 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen ( p < 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms ( p < 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively). In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.

223.5: Biodegradable stent for biliary reconstruction in pediatric liver transplantation, surgical approach.

223.5: Biodegradable stent for biliary reconstruction in pediatric liver transplantation, surgical approach.

364.3: Risk factors and outcomes of neutropenia following pediatric liver transplantation.

364.3: Risk factors and outcomes of neutropenia following pediatric liver transplantation.

301.4: Vacuum-assisted laparostomy for delayed abdominal closure in pediatric liver transplantation: A case series.

301.4: Vacuum-assisted laparostomy for delayed abdominal closure in pediatric liver transplantation: A case series.

V-212.3: Living donor versus deceased donor in pediatric liver transplantation: A systemic review.

V-212.3: Living donor versus deceased donor in pediatric liver transplantation: A systemic review.

P.487: Alloactivation has a key role in biopsy-proven acute rejection in pediatric liver transplant.

P.487: Alloactivation has a key role in biopsy-proven acute rejection in pediatric liver transplant.

Long-term outcomes and risk factors for early bacterial infection after pediatric liver transplantation: a prospective cohort study.

Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT. In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data. Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16). In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.

P.404: Portal inflow modulation in pediatric partial liver transplantation: Insights from a prospective study.

P.404: Portal inflow modulation in pediatric partial liver transplantation: Insights from a prospective study.

P.401: Plasma cell-rich rejection significantly impacts graft survival in paediatric liver transplantation recipients.

P.401: Plasma cell-rich rejection significantly impacts graft survival in paediatric liver transplantation recipients.

P.495: A review on the roles of mTOR inhibitors in pediatric liver transplant recipients.

P.495: A review on the roles of mTOR inhibitors in pediatric liver transplant recipients.

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.

364.1: Survival benefit of living donor availability for pediatric liver transplantation in a large North American center: An intention-to-treat analysis.

364.1: Survival benefit of living donor availability for pediatric liver transplantation in a large North American center: An intention-to-treat analysis.

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.

P.485: Fast track living donor protocol for pediatric liver transplant, the speed that saved lives.

P.485: Fast track living donor protocol for pediatric liver transplant, the speed that saved lives.

Risk Factors for Returning of Pediatric Liver Transplant Recipients to the Intensive Care Unit

Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.