Anna M. Banc-Husu

Background: Gestational alloimmune liver disease is the most common cause of acute liver failure in neonates. Treatment includes exchange transfusion and IVIG, though a subset of neonates requires liver transplantation for survival. Methods: We conducted a retrospective study using the Organ Procurement and Transplantation Network database and an institutional case series to characterize waitlist outcomes and patient survival among transplanted patients with gestational alloimmune liver disease. Results: 81 candidates were registered on the liver transplant waitlist with a neonatal hemochromatosis diagnosis code from October 1987 through March 2025. Of these, 36 (44.4%) received a liver transplant. Re‐transplantation was required in 6 (16.7%) patients. Four patients developed graft failure within the first year of transplant, 3 (75%) of which were due to hepatic artery thrombosis. Patient survival was 88.8% at 30 days, 82.7% at 1 year, and 79.5% at 5 years. Of the 45 candidates (55.6%) who did not receive a transplant, 20 (24.7% of all listed) died on the waitlist, 15 (18.5%) experienced improvement and ultimately did not need transplant, 8 (9.9%) were too sick to transplant, 1 (1.2%) was removed for other reasons, and 1 (1.2%) was transferred to another center. Among the institutional case series, three neonates presented with acute liver failure with workup consistent with GALD. All three were listed as status 1A, underwent successful liver transplant, and are alive present day. Conclusions: Liver transplant should be offered without hesitation for treatment‐refractory GALD. Early referral to a transplant center should occur simultaneously with initiation of medical therapy.

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: Human adenovirus in immunocompromised patients can be life‐threatening. We describe the prevalence, clinical presentation, and treatment of adenovirus after pediatric liver transplantation at a large transplant center. Methods: We performed a retrospective cohort study of adenovirus infection in children from 2013 to 2022. We compared incidence, clinical characteristics, and outcomes of post‐transplant children by adenovirus treatment status. Results: Adenovirus disease developed in 26% (84/320) children after liver transplant. Median age at liver transplant was 17.5 months, 48% were female; 50% had biliary atresia. Fever (53%), gastrointestinal symptoms (48%), and hepatitis (41%) were the most common clinical presentations at diagnosis. Median time to adenovirus diagnosis was 80 days (IQR 19–260) with 40% ( n = 31/84) identified within 30 days post‐transplant. Disseminated adenovirus (≥ 2 organ involvement) occurred in 24% (20/84). Fourteen patients (17%) received cidofovir, and most (13/14, 93%) had DNAemia, compared to 57% untreated patients with DNAemia ( p = 0.013). Median peak adenovirus load was 491 805 copies/mL (IQR 24 800–1 900 000) in treated vs. 1000 copies/mL (IQR 595–794 794) in untreated patients ( p < 0.001). Overall mortality was 8% (7/84). Conclusion: The incidence of symptomatic and disseminated adenovirus disease was high in our pediatric liver transplant patients, particularly within 30 days post‐transplant. Patients who received cidofovir treatment presented with high viral load and had the highest mortality. There is a critical need for evidence‐based guidance for early antiviral management of adenovirus disease after pediatric liver transplant.

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear. Methods: In this single‐center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen‐based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for the cohort). Results: Seventy‐two children (44 with chronic liver disease, 15 with acute liver failure, and 13 with acute‐on‐chronic liver failure), with a median age of 39 (IQR 13–159) months, were included. Twelve children (17%) had significant intraoperative bleeding. Most ROTEM parameters and the corresponding SCAs strongly correlated, except for EXTEM CT and INR (Rho of 0.501 and confidence interval (CI) of 0.298–0.660). A combination of SCA parameters performed better than the combination of corresponding ROTEM parameters (area under the curve of 0.862 vs. 0.760; p = 0.029) in predicting significant intraoperative bleeding. Among coagulation parameters, only platelet count was associated with significant intraoperative bleeding (adjusted Odds Ratio of 1.02, CI of 1.00–1.04; p = 0.009). Conclusions: ROTEM parameters and SCAs have comparable predictive value for significant intraoperative bleeding in children with LF requiring OLT. Further investigation is required to assess how ROTEM can be effectively used in managing coagulopathy in pediatric LF.

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.

Background: Biliary strictures (BS) remain a challenge in pediatric liver transplant (LT). Achievement of the “Optimal Biliary Outcome” (OBO), stricture resolution without recurrence or surgery is the goal. We analyzed cost associated with different management.Methods: Society of Pediatric LT (SPLIT) data were matched with Pediatric Health Information System (PHIS) data by dates of birth and transplant, center and sex. SPLIT data were used to identify LT recipients (2011–2016) with BS. Procedure and admissions costs from PHIS were inflation‐adjusted to 2022. Sub‐analyses evaluated costs associated with achieving OBO.Results: Optimal biliary outcome was achieved in 42% of 77 participants following a median of 4 procedures and 2 inpatient nights compared to a median of 7 procedures and 4 nights in those without OBO (p < 0.001). BS management was lower in participants who achieved OBO versus who did not achieve OBO (p = 0.004). Significant center variation in cost was observed (p < 0.001). Biliary strictures diagnosed earlier post‐PLT were associated with lower costs per patient (p = 0.049), while those who underwent surgical biliary revision did not incur higher costs per patient (p = 0.17). In participants who did not achieve OBO and underwent ≥ 6 PTC procedures tended to incur much higher costs compared to those who underwent ≤ 5 PTC procedures, regardless of surgical biliary revision (p = 0.08).Conclusions: Biliary stricture management costs were highest in patients requiring treatment for recurrence or surgical biliary revision and lowest earlier post‐transplant, suggesting that more aggressive management upfront may optimize costs. Future work will explore practice variation and cost‐effective strategies to achieve OBO.

Background: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life‐threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT.Methods: We conducted a retrospective cohort study of all children requiring CRRT pre‐OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post‐LT outcomes were compared between those who received iCRRT and those who did not.Results: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One‐year post‐LT mortality rates were similar.Conclusion: ICRRT is safe in critically ill children with pre‐LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource‐intensive therapy to benefit this fragile population.