Wadera, Sheetal

Background T cell–mediated hepatitis is an uncommon cause of acute pediatric liver injury. Most patients respond to steroids, but management of refractory disease remains challenging. We describe four patients with non-monogenic CD8+ T cell–mediated hepatitis with close temporal presentation and variable response to therapies. All four patients had severe elevations in liver enzymes, synthetic dysfunction, hyperbilirubinemia, cytopenias, elevations in cytokines (supplemental table), and CD8+ T cell predominance on biopsy, without meeting criteria for autoimmune hepatitis. All underwent next-generation or whole-exome sequencing; no monogenic causes were elucidated. Broad infectious workup was unrevealing. Case 1 A 17-year-old male with epilepsy presented with abdominal pain and jaundice, with labs and biopsy consistent with portal and lobular hepatitis with CD8+ T cell predominance. Bone marrow aspirate (BMA) was reassuring. Hepatitis was refractory despite corticosteroids, tacrolimus, sirolimus, anakinra, intravenous immune globulin (IVIG), and anti-thymocyte globulin (ATG). Infliximab led to dramatic but incomplete improvement. He remains on steroids, tacrolimus, and infliximab, with planned hematopoietic stem cell transplantation (HSCT). Case 2 A 7-year-old female with type 1 diabetes presented with jaundice and abdominal pain, with labs and biopsy consistent with CD8+ T cell hepatitis. Steroids induced a partial response, while infliximab led to marked improvement. She transitioned to azathioprine and maintains normal liver enzymes. Case 3 A 5-year-old male with autism presented with fevers and abdominal distention, with labs and biopsy consistent with portal and lobular hepatitis with CD8+ T cell predominance. IVIG/steroids provided only a transient improvement. Tacrolimus normalized labs and enabled steroid discontinuation. Case 4 An 11-month-old healthy female presented with jaundice. Labs and biopsy were consistent with giant cell hepatitis with CD8+ T cell predominance, and no evidence of autoimmune hemolytic anemia. She was listed for liver transplantation. Partial steroid response prompted tacrolimus initiation, leading to normalization of labs and removal from transplant listing. Conclusion CD8+ T cell–mediated hepatitis may progress rapidly and be steroid refractory. Early initiation of infliximab or tacrolimus may prevent progression to liver failure. Case one represents a severe presentation with limited response; however, most avoided liver or hematopoietic stem cell transplantation. All cases presented within a three-month window, suggesting a possible infectious trigger. Tabular data are included as downloadable supplement files.

ABSTRACT 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.

Purpose:Recent studies demonstrate the success of Kasai portoenterostomy for biliary atresia (BA) is linearly related to infant age at time of Kasai. We sought to review the feasibility and safety of laparoscopic needle micropuncture cholangiogram with concurrent core liver biopsy (if needed) for expedited exclusion of BA in patients with direct conjugated hyperbilirubinemia.Methods:Expedited laparoscopic cholangiogram and liver biopsy were instituted at our facility for infants with direct hyperbilirubinemia for whom clinical exam and laboratory workup failed to diagnose. A retrospective chart review was performed in infants <1 year with hyperbilirubinemia from 2016 to 2021. Demographics, preoperative evaluation, procedure details, and complications were reviewed.Results:Two hundred ninety‐seven infants with unspecified jaundice were identified, of which, 86 (29%) required liver biopsy. Forty‐seven percutaneous liver biopsies were obtained including 8 (17%) in whom BA could not be excluded. Laparoscopic cholangiogram was attempted in 47 infants following basic workup; BA was diagnosed in 22 infants (47%) of which 3 were <18 days old. Biliary patency was demonstrated laparoscopically in 22 of 25 (88%); 3 (12%) required conversion to open cholangiogram. Infants with percutaneous liver biopsy had an average delay of 3 days (range: 2–36) to cholangiogram. Preoperative studies and liver biopsy alone did not reliably exclude the diagnosis of BA.Conclusion:Laparoscopic cholangiogram with liver biopsy is a safe procedure resulting in the confirmation or exclusion of BA in infants. Forty‐seven percent of infants who underwent laparoscopic cholangiogram were found to have BA; those who were surgical candidates underwent Kasai during the same operation.