Pediatric Liver Transplantation Research Articles

Surgical Site Infections After Pediatric Liver Transplantation-Impact of a Change in Perioperative Prophylactic Antibiotic Protocol.

In spite of improved survival rates after pediatric liver transplantation, infections remain major contributors to perioperative morbidity and mortality. This study aimed to understand the impact of type and duration of perioperative antibiotic prophylaxis (PAP) on the occurrence of surgical site infections (SSIs). In total, 125 patients who underwent liver transplantation between 2014 and 2020 were retrospectively included. Patients were categorized into two periods based on changes in the standard PAP regimen. Risk factors for SSIs were investigated, including the influence of PAP duration, antibiotic substances used, and abdominal patch placement using multivariable regression models. SSIs occurred in 23 (19%) of 119 analyzed patients and were not impacted by changes in the PAP regimen. The placement of an abdominal patch was a relevant risk factor for SSIs (odds ratio 3.81; 95% confidence interval [CI] 1.15-12.68). Longer PAP duration reduced the occurrence of SSIs by up to 4.6 percentage points (95% CI 0.0-9.1) per day, with its effect diminishing with longer duration. The choice of antibiotic substances for PAP changed after implementation of the new protocol, with a decline in vancomycin usage from 14% to 3%. The results of this study emphasize the need for evidence-based PAP regimens tailored to the unique needs of pediatric liver transplant recipients. The occurrence of SSIs remains complex and is influenced by various factors beyond the PAP regimen. Multicentric efforts to develop effective prevention strategies against SSIs in this vulnerable population are warranted.

Demonstrating the Non-inferiority of a Plastic Surgery Microscopic Technique for Hepatic Artery Anastomosis in Pediatric Liver Transplant: A Single-Institution Study.

Before advancements in liver transplantation, conditions such as acute liver failure, decompensated liver cirrhosis, and hepatocellular carcinoma were associated with poor prognosis. Orthotopic liver transplantation has since emerged as a curative treatment. Despite its benefits, liver transplantation can lead to complications, including hepatic artery thrombosis (HAT), which is especially significant in pediatric patients. This study evaluates the utility of microsurgical anastomosis by plastic surgeons in reducing postoperative HAT compared to standard loupe-assisted anastomosis performed by transplant surgeons. This retrospective chart review included pediatric patients who underwent orthotopic liver transplantation at a single institution between September 2015 and September 2023. Patients were divided into two groups: one receiving standard loupe-assisted anastomosis by transplant surgeons (n = 28) and the other receiving microsurgical anastomosis by plastic surgeons (n = 22). The primary outcomes measured were the rates of HAT. Secondary outcomes included graft survival, patient survival, postoperative hospital stay, resistive indices, bleeding, biliary complications, venous complications, transplant rejection, and reoperation rates. In 50 pediatric patients who underwent orthotopic liver transplantation, we compared outcomes between standard anastomosis (n = 28) and microscope-assisted anastomosis (n = 22). Demographic characteristics were similar between the groups. Hemorrhage occurred significantly more frequently in the standard anastomosis group (35.7%) compared to the microscope-assisted group (9.1%), with a p-value of 0.045. Other complications, including HAT (28.6% vs. 13.6%, p = 0.306), biliary leak (14.3% vs. 27.3%, p = 0.302), and organ rejection (21.4% vs. 13.6%, p = 0.713), did not differ significantly between the groups. Additionally, survival rates were comparable, with 71% in the standard group and 86% in the microscope group (p = 0.306). These findings suggest that while microscope-assisted anastomosis may reduce the risk of hemorrhage, other outcomes remain similar between the techniques. Our findings suggest that microsurgical anastomosis techniques performed by plastic surgeons are non-inferior to standard loupe-assisted techniques in pediatric liver transplantation and may decrease the rate of postoperative hemorrhage. Microsurgical anastomosis is a viable alternative to standard loupe-assisted techniques in pediatric hepatic artery transplants. Further research with larger sample sizes is warranted to confirm these findings and optimize surgical techniques.

Adult provider role in transition of care for young adult pediatric recipients of liver transplant: An expert position statement.

Health care transition (HCT) is the process of changing from a pediatric to an adult model of care. Young adult pediatric recipients of liver transplant transferring from pediatric to adult health care services are highly vulnerable and subject to poor long-term outcomes. Barriers to successful transition are multifaceted. A comprehensive HCT program should be initiated early in pediatrics and continued throughout young adulthood, even after transfer of care has been completed. It is critical that pediatric and adult liver transplant providers establish a partnership to optimize care for these patients. Adult providers must recognize the importance of HCT and the need to continue the transition process following transfer. While this continued focus on HCT is essential, current literature has primarily offered guidance for pediatric providers. This position paper outlines a framework with a sample set of tools for the implementation of a standardized, multidisciplinary approach to HCT for adult transplant providers utilizing "The Six Core Elements of HCT." To implement more effective strategies and work to improve long-term outcomes for young adult patients undergoing liver transplant, HCT must be mandated as a routine part of posttransplant care. Increased advocacy efforts with the additional backing and support of governing organizations are required to help facilitate these practices.

The role of music therapy in supporting paediatric liver transplant recipients: a holistic approach

The role of music therapy in supporting paediatric liver transplant recipients: a holistic approach

Modified by the Innovative Drugs and Strategies-Pattern of Selected Indications for Pediatric Liver Transplantation.

Liver transplantation (LTx) constitutes a major life-saving routine treatment for children with end-stage liver disease. However, the analysis of LTx registries in children provides much information about changes in the indication profiles in the recent years. The article provides a comprehensive review about the successes, hopes, and challenges related to changing indications for LTx in children based on the literature review and our own experience. Retrospective review of the indications for LTx at a tertiary referral pediatric hospital was also presented. In the context of the new therapies that have emerged, the need for LTx has decreased in patients with chronic hepatitis B and C infection and tyrosinemia type 1. In primary hyperoxaluria type 1, new RNAi-based therapy has eliminated the requirement for LTx (both isolated or combined). There is a hope that introduction of ileal bile acid transporter (IBAT) blockers reduces the need for LTx in patients with Alagille syndrome or progressive familial intrahepatic cholestasis. The number of children qualified for LTx with urea cycle disorders (UCDs) as a prophylaxis of neurodevelopmental impairment is increasing.

Elastography-The New Standard in the Assessment of Fibrosis After Pediatric Liver Transplantation?

The development of graft fibrosis after pediatric liver transplantation (PLT) remains a major concern as it can lead to graft failure and ultimately graft loss. Elastography is a non-invasive method to assess liver fibrosis, but its role in the posttransplant setting is unclear. The aim of our study was to evaluate shear wave elastography (SWE) in the assessment of liver fibrosis after PLT, including split-liver recipients. We retrospectively analyzed data from PLT recipients who underwent surveillance liver biopsy and concurrent 2D-SWE during the study period from April 2018 to July 2021. Spearman's correlation was used to compare histologic fibrosis stages with liver stiffness measurements (LSM) by 2D-SWE. AUROC analysis was performed to evaluate the performance. One sample t-test was used to compare results with reference values of healthy children. 62 cases were included. 29% showed histologic fibrosis. LSM by 2D-SWE were feasible in all children regardless of age or graft type. There was a significant correlation between LSM and fibrosis stage for all three scoring systems used (Ishak, p = 0.003; METAVIR, p = 0.005; LAF Score, p = 0.003). Patients with a history of biliary complications had increased liver stiffness (p = 0.015). The AUROC of 2D-SWE for predicting significant liver graft fibrosis was 0.81. Liver stiffness after PLT without graft fibrosis was higher than in healthy subjects, but comparable to that in children with chronic liver disease without fibrosis. 2D-SWE can reliably detect children with significant liver graft fibrosis, even in split-liver recipients. This study demonstrates the value of a non-invasive tool for fibrosis staging after PLT. 2D-SWE has the potential to improve long-term outcomes after PLT and to reduce the number of surveillance liver biopsies. But elastography is not a substitute for liver biopsy.

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.

Perioperative management in pediatric domino liver transplantation for metabolic disorders: A narrative review.

Domino liver transplantation and domino-auxiliary partial orthotopic liver transplantation are emerging techniques that can expand the liver donor pool and provide hope for children with liver disease. The innovative technique of domino liver transplantation has emerged as a pioneering strategy, capitalizing on structurally preserved livers from donors exhibiting single enzymatic defects within a morphologically normal context, effectively broadening the donor pool. Concurrently, the increasingly prevalent domino-auxiliary partial orthotopic liver transplantation method assumes a critical role in bolstering available donor resources. These advanced transplantation methods present a unique opportunity for pediatric patients who, despite having structurally and functionally intact livers and lacking early signs of portal hypertension or extrahepatic involvement, do not attain priority on conventional transplant lists. Utilizing optimal clinical conditions enhances posttransplant outcomes, benefiting patients who would otherwise endure extended waiting periods for traditional transplantation. The perioperative management of children undergoing these procedures is complex and requires careful consideration of some factors, including clinical and metabolic conditions of the specific metabolic disorder, and the need for tailored perioperative management planning. Furthermore, the prudent consideration of de novo disease development in the recipient assumes paramount significance when selecting suitable donors for domino liver transplantation, as it profoundly influences prognosis, mortality, and morbidity. This narrative review of domino liver transplantation will discuss the pathophysiology, clinical evaluation, perioperative management, and prognostic expectations, focusing on perioperative anesthetic considerations for children undergoing domino liver transplantation.

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 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 sirolimus 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 postsirolimus 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 sirolimus treatment owing to nephrotic proteinuria. In conclusion, sirolimus may be a safe and effective treatment for chronic and steroid-resistant rejection and may improve allograft rejection-related fibrosis and ductal damage.

Renal Assessment in the Setting of Pediatric Living Related Liver Transplantation

Abstract Background Liver transplantation in the pediatric age group has become the last resort and yet the preferred option for many end stage liver disorders. This field shows a great improvement and is considered a breakthrough achievement for previously fatal liver diseases. Renal functions are not thoroughly studied in pediatric patients undergoing liver transplantation. Aim of the Work To determine the prevalence and risk factors of renal dysfunction among pediatric living related liver transplantation (LRLT). Patients and Methods This was a cross sectional retrospective and prospective cohort study in which a pilot study for a six-month duration is estimating the incidence of renal dysfunction among LRLT. A total of 40 patients were enrolled during the duration of the study from Ain Shams University, pediatric hospital and Dr. Yassin Abdel Ghaffar charity center for liver disease and research. Full history and clinical examination was performed as well as base line investigations preoperatively including: Serum Creatinine, Urea, Na, K, PO4, Ca, corrected creatinine clearance and urine analysis. Post-operative assessment was done to same parameters in addition to: Serum Mg, Cl, HCO, uric acid, drug trough level of used immunosuppressive drugs, 24 hours’ urinary proteins, and 24 hours’ assessment of electrolytes (Na, K, Ca, PO4, HCO3) in case of lowered serum levels. Moreover, pre and postoperative pelviabdominal U/S to check kidney status (size, echogenicity, RI of renal arteries) was assessed. Results Forty patients were analyzed of which 70% of the patients were males. The mean age at transplantation was 6.84±3.3 years. The commonest diagnosis of the studied group was high gamma-glutamyl transferase (GGT) cholestasis (35%) followed by Biliary atresia (22.5%). Of the enrolled patients, 50% were CHILD-B score, the median of the CHILD Score prior to transplantation was 8 and the median of the PELD score was 7.4. 87.5% of the patients had normal urine analysis, and normal proteinuria in 100% of the patients. The postoperative laboratory investigations were within the normal ranges. Mg was low in 67% of patients while Ca was low in 42.5%.The mean of creatinine, K and Ca levels are significantly elevated after LT (P < 0.05). After a mean duration since transplantation of 4 years, we found that 82.5% of our patients were CKD G1. S. creatinine was positively correlated with the patient age, duration of transplantation, s. uric acid, and average Fk level over the past year(P < 0.05 for all). Conclusion Renal dysfunction is a common, yet may be an underestimated, problem after pediatric liver transplant. Renal impairment was limited in our patients probably due to favorable perioperative conditions. Our pediatric recipients require mandatory and planned nephrologic evaluation to early detect any renal impairment which may develop into an end-stage renal disease and eventually increase the patient mortality rate. Further studies with larger cohort of patients and more advanced methods of assessment of renal functions are recommended.

Cytokine Dynamics and Herpesvirus Interactions in Pediatric Liver and Kidney Transplant Recipients: The Distinct Behavior of HCMV, HHV6, HHV7 and EBV.

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients.

Lack of differences in outcomes between 3 immunosuppression protocols in the first year after pediatric liver transplantation: A multicenter study.

Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference. We aimed to compare 3 different protocols from 4 different centers to identify differences in outcomes after 1 year of follow-up. A retrospective analysis of the databases of the participating centers was performed. Consecutive patients aged <18 years with a first liver-only transplant and no other underlying congenital or acquired immunodeficiency were included. Patients were classified according to the immunosuppression protocol as follows: group A (prednisone + tacrolimus + basiliximab), group B (prednisone + tacrolimus + basiliximab + antithymocyte globulin), and group C (prednisone + tacrolimus). Differences in survival, frequency of rejection, infections, and other complications were analyzed in the entire group (n = 97) and the group with biliary atresia (n = 48). After 1 year of follow-up, no differences in patient or graft survival were observed when comparing either the entire group (n = 97) or patients with biliary atresia only (n = 48). The frequencies of rejection and episodes of infection were similar. Renal function showed no differences either before or after transplantation or between the groups. Immunosuppression protocols used in this study appeared to be equally safe and effective. This could offer the opportunity to tailor them to the patient's individual characteristics without compromising the outcome.

Pediatric liver transplant in India: Still in infancy or coming of age

Pediatric liver transplant in India: Still in infancy or coming of age

Constructing an Intent-to-Treat Score Index to Predict Survival Outcomes in Pediatric Liver Transplant Recipients.

Waitlist and posttransplant outcomes have been widely reported for pediatric liver transplantation. Yet, analyzing these metrics individually fails to provide a holistic perspective for patients and their families. Intent-to-treat (ITT) analysis fills this gap by studying the associations between waitlist outcomes, organ availability, and posttransplant outcomes. Our study aimed to construct a predictive index utilizing ITT analysis for pediatric liver transplant recipients (Pedi-ITT). We performed a retrospective analysis utilizing de-identified data provided by the United Network for Organ Sharing (UNOS) from March 1, 2002, to December 31, 2021. We analyzed data for 12 926 pediatric recipients (age <18). We conducted a univariate and multivariable logistic regression to find the significant predictive factors affecting ITT survival. A scoring index was constructed to stratify outcome risk on the basis of the significant factors identified by regression analysis. Multivariable analysis found the following factors to be significantly associated with death on the waitlist or after transplant: gender, diagnosis, UNOS region, ascites, diabetes mellitus, age at the time of listing, serum sodium at the time of listing, total bilirubin at the time of listing, serum creatinine at the time of listing, INR at the time of listing, history of ventilator use, and history of re-transplantation. Using receiver operator characteristic analysis, the Pedi-ITT index had a c-statistic of 0.79 (95% confidence interval [CI]: 0.76-0.82). The c-statistics of the Model for End-Stage Liver Disease/Pediatric for End-Stage Liver Disease and pediatric version of the Survival Outcomes Following Liver Transplantation score indices were 0.74 (CI: 0.71-0.76) and 0.69 (CI: 0.66-0.72), respectively. The Pedi-ITT index provides an additional prognostic model with moderate predictive power to assess outcomes associated with pediatric liver transplantation. Further analysis should focus on increasing the predictive power of the index.

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.

Treatment Strategies for Bile Leak Following Pediatric Liver Transplantation.

Retrospective analysis (January 2010-March 2023). preoperative data, status at diagnosis, and postoperative outcome. Four groups: observation (n = 9), percutaneous transhepatic cholangiography (PTC, n = 38), ERCP (2), and surgery (n = 27). Nine hundred and thirty-one pediatric liver transplantation (859 LDLT and 72 DDT); 78 (8.3%) patients had BL, all in LDLT. The median (IQR) peritoneal bilirubin (PB) level and fluid-to-serum bilirubin ratio (FSBR) at diagnosis was 14.40 mg/dL (8.5-29), and 10.7 (4.1-23.7). Patients who required surgery for treatment underwent the procedure earlier, at a median of 14 days (IQR: 7-19) versus 22 days for PTC (IQR: 15-27, p = 0.002). PB and FSBR were significantly lower in the observation group. In 11 cases, conservative management had resolution of the BL in an average time of 35 days, and 38 patients underwent PTC in a median time of 22 days (15-27). Twenty-seven (34.6%) patients were reoperated as initial treatment for BL in a median time of 17 days (1-108 days); 25 (33%) patients evolved with biliary stricture, 5 (18.5%) after surgery, and 20 (52.6%) after PTC (p = 0.01). Patients with BL who were observed presented significantly lower levels of PB and FSBR versus those who underwent PTC or surgery. Patients treated with PTC presented higher rates of biliary stricture during the follow-up.

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.

Postoperative hypoalbuminemia and outcomes of pediatric liver transplantation

BackgroundHypoalbuminemia after liver transplantation (LT) is associated with acute kidney injury (AKI) and poor outcomes in adult LT recipients. This study was performed to examine the association between the postoperative serum albumin level and early postoperative outcomes of LT in children.MethodsThis single-center retrospective review involved pediatric LT recipients (0–18 years old) treated from January 2013 to June 2020. All patients were admitted to PICU and received standard post-LT care protocol. We divided patients into low (< 30 g/L) and normal (> 30 g/L) groups based on postoperative albumin day 1 to 3.ResultsAmong 108 LT recipients, most had biliary atresia. The median age at the time of LT was 1.8 years [interquartile range (IQR), 1.5–5.7]. There were 18 patients in low albumin group [median albumin level, 27.9 g/L (IQR, 25.8–29.6) and 90 patients in normal albumin group [median albumin level, 34.5 g/L (IQR, 32.4–36.9). The low albumin group had significantly higher incidence of AKI, occurring in 20% of patients with a median onset of 2.5 days following LT (IQR, 1–5). Postoperative hypoalbuminemia (OR, 4.94; 95% CI, 1.32–18.47; p = 0.01) and a longer operative time (OR, 1.37; 95% CI, 1.01–1.47; p = 0.02) were independent risk factors for AKI by multivariable analysis. No significant differences between the two groups were found in other early postoperative outcomes.ConclusionPostoperative hypoalbuminemia was associated with early postoperative AKI following LT in children but not with other worsening outcomes.

Specific binding sites on Rhesus rotavirus capsid protein dictate the method of endocytosis inducing the murine model of biliary atresia.

Biliary atresia (BA) is the leading indication for pediatric liver transplantation. Rhesus rotavirus (RRV)-induced murine BA develops an obstructive cholangiopathy that mirrors the human disease. We have previously demonstrated the "SRL" motif on RRV's VP4 protein binds to heat shock cognate 70 protein (Hsc70) facilitating entry into cholangiocytes. In this study, we analyzed how binding to Hsc70 affects viral endocytosis, intracellular trafficking, and uniquely activates the signaling pathway that induces murine BA. Inhibition of clathrin- and dynamin-mediated endocytosis in cholangiocytes following infection demonstrated that blocking dynamin decreased the infectivity of RRV, whereas clathrin inhibition had no effect. Blocking early endosome trafficking resulted in decreased viral titers of RRV, whereas late endosome inhibition had no effect. After infection, TLR3 expression and p-NF-κB levels increased in cholangiocytes, leading to increased release of CXCL9 and CXCL10. Infected mice knocked out for TLR3 had decreased levels of CXCL9 and CXCL10, resulting in reduced NK cell numbers. Human patients with BA experienced an increase in CXCL10 levels, suggesting this as a possible pathway leading to biliary obstruction. Viruses that use Hsc70 for cell entry exploit a clathrin-independent pathway and traffic to the early recycling endosome uniquely activating NF-κB through TLR3, leading to the release of CXCL9 and CXCL10 and inducing NK cell recruitment. These results define how the "SRL" peptide found on RRV's VP4 protein modulates viral trafficking, inducing the host response leading to bile duct obstruction.NEW & NOTEWORTHY In this study, we have determined that the presence of the "SRL" peptide on RRV alters its method of endocytosis and intracellular trafficking through viral binding to heat shock cognate 70 protein. This initiates an inflammatory pathway that stimulates the release of cytokines associated with biliary damage and obstruction.

HOPE Mitigates Ischemia-Reperfusion Injury in Ex-Situ Split Grafts: A Comparative Study With Living Donation in Pediatric Liver Transplantation.

Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT). All consecutive HOPE-Split, SCS-Split and LDLT performed between 2018-2023 for pediatric recipients were included. Post-reperfusion syndrome (PRS, drop ≥30% in systolic arterial pressure) and reperfusion biopsies served as early indicators of IRI. We included 47 pediatric recipients (15 HOPE-Split, 17 SCS-Split, and 15 LDLT). In comparison to SCS-Split, HOPE-Split had a significantly shorter cold ischemia time (CIT) (470min vs. 538min; p =0.02), lower PRS rates (13.3% vs. 47.1%; p = 0.04) and a lower IRI score (3 vs. 4; p = 0.03). The overall IRI score (3 vs. 3; p = 0.28) and PRS (13.3% vs. 13.3%; p = 1) after HOPE-Split were comparable to LDLT, despite a longer CIT (470min vs. 117min; p < 0.001). Surgical complications, one-year graft, and recipient survival did not differ among the groups. In conclusion, HOPE-Split mitigates early IRI in pediatric recipients in comparison to SCS-Split, approaching the gold standard of LDLT.