Moreshwar. S. Desai

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.

Hepatorenal syndrome (HRS-AKI) confers significant morbidity and mortality in patients with cirrhosis. Cirrhotic cardiomyopathy (CCM), a prevalent comorbidity in adults with growing recognition in children, leads to hemodynamic perturbations that may compound the maladaptive physiology resulting in HRS-AKI. We aimed to explore a hepato-cardio-renal link in pediatric cirrhosis by examining peritransplant AKI, with a focus on CCM and Major Adverse Kidney Events at 28 days (MAKE28) in patients undergoing liver transplant (LT). This is a single-center, retrospective study of pediatric LT for biliary atresia (BA) from 2014 to 2020. Peri-LT AKI was defined as AKI within 7 days of LT. CCM was defined as left ventricular mass index to height of ≥95 g/m ^2.7 , and/or relative wall thickness ≥0.42. Of 62 patients with BA (age 1.1 y [IQR: 0.8–2.4]), 29% had AKI, 61% had CCM, and 40% fulfilled MAKE28. Patients with AKI had higher blood product and vasoactive requirements, and lower ventilator-free days, compared with patients without AKI. The median length of stay was 133 (IQR: 54–121) versus 19.5 (IQR: 8.5–41) days for patients with AKI and without AKI, respectively ( p p =0.005). CCM remained significant after adjusting for age, markers of liver disease severity, and intraoperative events. Patients with BA face high morbidity peri-LT in the setting of prevalent AKI. The association between pediatric CCM and AKI suggests that cardiac dysfunction may be an independent risk factor for HRS-AKI. While studies are needed to further define the relationship between CCM and renal injury, pre-LT echocardiogram has the potential to facilitate timely identification and management of children at risk for HRS-AKI, and thereby promote renal recovery.

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 nutrition support of children with biliary atresia after liver transplant is affected by multiple factors, and a connection between these factors and conditions present before transplant can potentially make the nutrition support more challenging. We aim to assess the adequacy of nutrition support, specifically energy and protein, during the first week of admission to the Pediatric Intensive Care Unit (PICU) in children after liver transplant secondary to biliary atresia. Methods: We performed a retrospective cohort study of 138 patients [13.9 median (9–33.4) IQR months; 62% female] with a diagnosis of biliary atresia admitted to the PICU after liver transplantation at Texas Children’s Hospital over a 14-year study period. We obtained nutrition adequacy of enteral and parenteral nutrition support for the first week after transplant during their PICU admission. Results: Goal adequacy was reached at the end of the first week of admission when combined enteral and parenteral nutrition support was provided (median 98% for energy and 101% for protein). Infants achieved significantly higher adequacies than older children during the first week (136% < 1 year vs. 0% > 1 year, p < 0.001 for calories, and 157% < 1 year vs. 0% > 1 year for protein; p < 0.01). Conclusions: These findings highlight the complex nutritional challenges faced by this population, and strategies are needed to meet the unique needs of children after liver transplantation.

Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.

Introduction: Acute‐on‐chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse.Method: We performed a retrospective analysis of patients with BA aged p < .001) and at LT (8 [8–11] vs. 16 [10–40] months, p < .001) compared to no‐ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20–53] vs. 10 [6–19] mL/kg; p < .001) and blood transfusion requirements (33 [21–69] vs. 18 [7–25] mL/kg; p = .004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p = .04) and had higher total hospital length of stay (106 [45–151] vs. 13 [7–30] days; p = .023). Rate of return to the operating room, hospital readmission rates, and 1‐year post‐LT survival rates were comparable between the groups.Conclusion: Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT.

Our studies provide experimental evidence for P2Y2 purinergic receptor-mediated potentiation of inflammatory liver injury, morbidity, and mortality, in two well-established animal models of inflammatory liver injury. Our findings highlight the potential to target P2Y2 purinergic signaling to attenuate the induction of “cytokine storm” and prevent its deleterious consequences on liver function, systemic amino acid homeostasis, host response to bacterial infection, and sepsis-associated morbidity and mortality.

Background: Children at high risk for prolonged mechanical ventilation (PMV) after liver transplantation (LT) need to be identified early to optimize pulmonary support, allocate resources, and improve surgical outcomes. We aimed to develop and validate a metric that can estimate risk for Prolonged Ventilation After LT (PROVE‐ALT).Methods: We identified preoperative risk factors for PMV by univariable analysis in a retrospective cohort of pediatric LT recipients between 2011 and 2017 (n = 205; derivation cohort). We created the PROVE‐ALT score by mapping multivariable logistic regression coefficients as integers, with cutoff values using the Youden Index. We validated the score by C‐statistic in a retrospectively collected separate cohort of pediatric LT recipients between 2018 and 2021 (n = 133, validation cohort).Results: Among total 338 patients, 21% (n = 72) were infants; 49% (n = 167) had cirrhosis; 8% (n = 27) required continuous renal replacement therapy (CRRT); and 32% (n = 111) required management in hospital (MIH) before LT. Incidence of PMV post‐LT was 20% (n = 69) and 3% (n = 12) required tracheostomy. Independent risk factors (OR [95% CI]) for PMV were cirrhosis (3.8 [1–14], p = .04); age p = .001); need for preoperative CRRT (6.3 [1.2–32], p = .02); and MIH before LT (12.4 [2.1–71], p = .004). PROVE‐ALT score ≥8 [Range = 0–21] accurately predicted PMV in the validation cohort with 73% sensitivity and 80% specificity (AUC: 0.81; 95% CI: 0.71–0.91).Conclusion: PROVE‐ALT can predict PMV after pediatric LT with a high degree of sensitivity and specificity. Once externally validated in other centers, PROVE‐ALT will empower clinicians to plan patient‐specific ventilation strategies, provide parental anticipatory guidance, and optimize hospital resources.

Background: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. Methods: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. Results: In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. Conclusion: This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.