Scott A. Elisofon

Background: Ascending cholangitis, one of the most common complications in patients with biliary atresia (BA) after Kasai hepatoportoenterostomy (HPE), impacts native liver survival. Typically, enteric bacterial flora are the source of infection, and fungal infections of the biliary tree are rare. Case Report: We report the case of a 3‐year‐old female with BA status post Kasai HPE who developed Aspergillus terreus cholangitis (complicated by hepatic vein thrombus) identified through plasma metagenomic next‐generation sequencing (NGS) of microbial cell‐free deoxyribonucleic acid (DNA). Despite improvement in galactomannan (GM) antigen indices while on antifungal therapy with voriconazole and anticoagulation, she experienced complications with the extension of septic thrombus and persistent cholestasis; thrombus tissue sampling later confirmed the diagnosis and antimicrobial sensitivities. Ultimately, native liver explantation succeeded in achieving source control with sustained normalization of GM indices after the completion of voriconazole. Post‐transplant, she received routine immunosuppression and infection prophylaxis per institutional protocol and remains well without infectious complications more than 1 year later. Discussion: This case highlights the important role of newer molecular diagnostic tools in facilitating timely species‐level pathogen identification and initiation of targeted therapy (in this case, 35 days prior to confirmed tissue diagnosis), particularly in circumstances where the risk‐to‐benefit ratio of invasive tissue sampling is unfavorable. Despite the significant morbidity associated with invasive fungal infection, transplantation followed by standard immunosuppression is a reasonable therapeutic option with successful outcomes in patients who are otherwise suitable transplant candidates.

Background: Disparities exist in pediatric liver transplantation in the United States. Clinician perspectives on how patient and family social and psychosocial factors affect patient selection remain unknown. Methods: A national, cross‐sectional, mixed‐methods survey was distributed to pediatric liver transplant committee members (June–November 2024). The survey assessed respondent and center characteristics, voting/conflict resolution practices, perceived influence of professional roles, social and psychosocial listing challenges, and moral distress. Quantitative analysis included descriptive statistics and multivariable linear/logistic regression; free‐text responses underwent thematic analysis. Results: Among 162 eligible complete surveys, respondents represented multiple committee roles and sociodemographic backgrounds. Listing decisions were typically made verbally, with conflicts resolved through discussion, ethics consultation, or transplant surgeon tie‐breaker vote. Professional role was strongly associated with perceived strength of voice, with physicians reporting substantially greater voice than non‐physicians. Respondents reported moderate moral distress related to listing decisions involving social and psychosocial concerns. In adjusted models, social workers/psychologists and women reported higher moral distress ratings; social workers/psychologists also had increased odds of greater moral distress frequency, although confidence intervals were wide. Key social concerns included patient/caregiver non‐adherence, mental health, housing instability, and insurance. Qualitative data identified that social and psychosocial factors often delay but do not contraindicate listing and require team collaboration. Conclusions: Patient/family social and psychosocial factors influence pediatric liver transplant selection and contribute to clinician moral distress. To promote justice and mitigate distress, advocacy should focus on optimizing patient and family support from the listing phase onward, clinician ethics education, and more balanced decision‐making frameworks.

Background and Aims: Management of portal hypertension in children, including primary prophylaxis of variceal bleeding, is controversial due to limited understanding of mortality risk after the first variceal hemorrhage (1VH). This international multicenter study was designed to advance understanding of outcomes after pediatric 1VH. Approach and Results: Center-specific characteristics and approaches to portal hypertension were determined at 44 international sites. K-means clustered the centers based upon volume and complexity of approaches [cluster 1 high (n=5), cluster 2 low (n=21), cluster 3 intermediate (n=18)]. Clinical features and outcomes after 1VH were available from 345 subjects. Factors associated with overall survival (OS) and survival with native liver (SNL) were estimated by Kaplan–Meier survival curves, log-rank tests, univariable and multivariable Cox regression models. OS and SNL were high in portal vein thrombosis and noncirrhotic diseases and significantly higher than biliary atresia and cirrhotic diseases ( p <.001). Diminished SNL was observed in decompensated disease [diuretics (ie, ascites) or hospitalization at 1VH], biliary atresia with poor bile flow, cirrhotic disease, after sclerotherapy, or no endoscopic intervention. Diminished OS was noted in those with cirrhosis or requiring sclerotherapy. Mortality at 6 weeks was determined and compared among clusters using the average treatment effect under the Rubin causal model. Overall, 6-week mortality was 4.1%, 1.4% in nonhospitalized subjects, and was significantly higher in cluster 2 versus 1 centers ( p =0.010). Conclusions: Immediate mortality after 1VH in children is low compared with adults. Outcomes after 1VH are diagnosis-specific and worse in decompensated disease and after sclerotherapy. Center-specific factors may influence immediate outcomes after 1VH.

Background: Activated T-cell pediatric acute liver failure (TC-PALF) is the most common cause of non-acetaminophen PALF, with poor transplant-free survival. Livers in TC-PALF are infiltrated by effector cytotoxic T lymphocytes with markers of tissue-resident memory function (CD8 Trm) and an interferon gamma (IFNγ) transcriptional signature. The PALF-Immune Response Network (PALF-IRN) and the prospective TReatment for ImmUne-Mediated PathopHysiology (TRIUMPH) clinical trial (NCT04862221) aim to characterize the TC-PALF immune pathology and utility of T-cell directed therapy to improve transplant-free survival. Methods: TRIUMPH patients with TC-PALF were compared with healthy children and disease controls utilizing multiparameter flow cytometry and 3′ single-cell RNA sequencing from peripheral blood mononuclear cells. TC-PALF patient serum was compared with healthy children and those with PALF from other causes, utilizing the Olink Inflammation I 384 protein assay. Results: Two distinct endotypes of TC-PALF were identified, which differed in flow cytometry CD8+ Perforin1 (Prf) expression and liver biopsy staining of Prf. TC-PALF patients with high CD8+ Prf (TC-PALF High Prf) had monocytosis, with a unique circulating CD8 IFNγ+ Trm-like population and IFNγ-responsive CD14/CD16 monocyte ligand–receptor interaction. TC-PALF patients with normal CD8+ Prf expression had hypergammaglobulinemia, an increase in class-switched B-cells, and a decrease in serum inflammatory proteins associated with myeloid activation. Conclusions: TC-PALF high Prf patients have a unique circulating CD8+ IFNγ+ Trm-like population accompanied by monocyte proliferation and activation. Further understanding of the role of IFNγ in TC-PALF High Prf may provide a therapeutic target for this endotype to improve transplant-free survival. Export

Background: The Society of Pediatric Liver Transplantation (SPLIT) has undergone tremendous growth with > 45 sites contributing data focusing on improving outcomes in pediatric liver transplantation (LT). We report and compare outcomes from the SPLIT Registry. Methods: Patients < 18 years with first‐time LT only enrolled into the SPLIT Registry between 2011 and 2023 were included. Data was stratified into eras from the last published registry update (era 1: 2011–2018, era 2: 2018–2023). Results: Three thousand five hundred four participants from 47 centers were included (era 1: n = 2159; era 2: n = 1345). Age distribution differed with more children < 1 year. of age at LT in era 2 (era 1: 29% vs. era 2: 33%, p = 0.01). Indications for LT were similar, with biliary atresia (38.8%) and metabolic disease (16.0%) being most common. Exception point use was higher in era 2 (era 1: 45% vs. era 2: 56%, p < 0.001). No difference in graft type (deceased: 81% era 1 vs. 78% era 2, p = 0.78), patient survival at 90 days (era 1: 98.7% vs. era 2: 98.3%), 1 year (era 1: 97.2 vs. era 2: 96.8%), or 3 years (era 1: 95.3% vs. era 2: 95.2%) was noted. Rate of hepatic artery thrombosis was lower in era 2 (era 1: 7% vs. era 2: 5%, p = 0.02). Conclusions: Trends in pediatric LT within SPLIT note similar LT indications and graft type, higher utilization of exception points, and lower HAT rates despite transplanting more children < 10 kg. This data underscores the evolution of pediatric LT toward higher survivability and overall patient outcomes.

Introduction: Allograft dysfunction within the first week posttransplant is an uncommon but known complication following liver transplantation. Seventh‐Day Syndrome (7DS) is a rare complication of allograft dysfunction following liver transplantation characterized by the rapid clinical deterioration of a formerly well‐functioning allograft within the first week posttransplant. The etiology of 7DS is unknown, and treatment options remain limited. While cases of graft survival have been reported, the risk of mortality remains exceedingly high without urgent retransplantation.Methods: Patient data was retrospectively analyzed and a literature review performed.Results: We present a unique case of split liver transplantation into two pediatric recipients in which one recipient developed rapidly progressive graft failure approximately 1 week postoperatively requiring urgent retransplantation while the other recipient had an unremarkable postoperative course. Upon clinical manifestation of progressive graft failure, the patient was treated with thymoglobulin, rituximab, intravenous immunoglobulin, and plasmapheresis. Despite this, the patient's clinical status continued to decline and she underwent retransplantation 11 days following her initial liver transplant.Conclusion: Seventh‐Day Syndrome is a rare complication following liver transplantation that is associated with a high risk of morbidity and mortality. Our case adds to the limited literature on 7DS in children and is the first to report a comparative posttransplant clinical course in two recipients who received split grafts from the same donor.

Background: Chronic kidney disease (CKD) impacts long‐term morbidity in pediatric liver transplant (LT) recipients. The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m² (eGFR < 90) at our institution was 25% at 1 year post‐LT; thus, quality improvement (QI) project was initiated, aiming to decrease the prevalence of eGFR < 90 by at least 20% at 1 year‐post LT.Methods: Children post‐LT under 19 years from 2010 to 2018 were included. Three QI interventions were implemented starting 1/2016: documentation of blood pressure percentile (BP%) and eGFR, documentation of a kidney management plan if either was abnormal, and amlodipine initiation prior to hospital discharge after LT. We compared the prevalence of eGFR < 90 at 3, 12, and 24 months after LT in the pre‐ and post‐intervention period.Results: 68 patients in pre‐ and 42 in post‐intervention periods met inclusion criteria. Pre‐intervention BP%, eGFR, and kidney management plan were documented at 25%, 10%, and 22%, compared to 71%, 83%, and 71% post‐intervention, respectively. 22% of patients were started on amlodipine prior to discharge from LT in the pre‐ versus 74% in the post‐intervention period. Prevalence of eGFR < 90 at 3 m post‐LT was 19% in pre‐ versus 14% in the post‐intervention period (p = .31); at 12 months 24% versus 7% (p = .01) and at 24 months 16% versus 6% (p = .13), respectively. Significant non‐modifiable risk factors for eGFR < 90 were malignancy (RR = 4.5, p < .0001), metabolic disorder (RR = 2.6, p = .02), and age at transplant (7% increased risk per year of age, p = .007).Conclusion: By improving documentation of BP%, eGFR, and kidney management plan, the prevalence of eGFR < 90 was decreased by a relative 74% and 60% at 12 and 24 months post‐LT, respectively.

TE measures liver stiffness to assess fibrosis. Its use in post‐transplant patients was reported in few small pediatric studies. We evaluated TE ability to predict liver graft fibrosis in a large cohort while comparing it to the performance of APRI and FIB‐4. We also investigated the effect of graft type on LSMs. Patients at Boston Children's Hospital who underwent LT and LSM ≤ 1 year from biopsy (2007‐2018) were eligible. Ninety‐four patients (45%M) aged 1‐21 years (89% < 18 years; 13% < 2 years) were eligible. Median time between transplant/biopsy and LSM was 5.1 years and 52 days, respectively. Thirty‐nine percent received whole‐liver grafts, 54% TV grafts, and 6% as part of MV. At LSM, median ALT was 25 [IQR 16‐33] IU/L. Twenty‐one percent had METAVIR ≥ F2. LSM was statistically higher among those with significant fibrosis (METAVIR ≥ F2) compared to those with METAVIR F0/F1 (median [IQR] 7.5 [4.6, 13.6] vs 5.1 [4.0, 6.4] kPa, respectively) (P = .005 by Wilcoxon rank‐sum test). APRI and FIB‐4 distributions were not different across METAVIR stages. The AUROC for LSM was 0.71 (95% CI 0.56‐0.85) with an optimal cut‐point of 6.5 kPa. Graft type had no influence on the AUROC for LSM. TE is useful for assessing significant graft fibrosis in children and young adult LT recipients and performs better than APRI and FIB‐4. TV grafts demonstrate similar correlation with histology as whole‐liver grafts.