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Background Human adenoviruses (HAdV) are a common cause of respiratory and gastrointestinal infections but rarely cause end-organ disease in children. From October 2021 to February 2022, several previously healthy children admitted to a single center for significant hepatitis also tested positive for HAdV. The aim of this investigation is to describe characteristics of these children. Methods Children admitted to Children’s of Alabama (COA) from October 2021 to February 2022 with hepatitis who tested positive for HAdV by whole blood RT-PCR were included. Demographic, clinical, laboratory and treatment data were collected from medical records. Residual blood specimens were sent for adenovirus typing. Results Nine pediatric patients with hepatitis and HAdV infection were identified (78% female; median age 3.0 years; IQR 1.7-3.0). Before admission, six reported diarrhea and three had respiratory symptoms. At presentation, eight had scleral icterus, six had jaundice, seven had hepatomegaly, and one was encephalopathic. All patients had elevated transaminases (AST range: 447-4000 U/L, ALT range: 784-4695 U/L); initial total bilirubin varied [range 0.23-13.5 mg/dL]). All had confirmed HAdV by RT-PCR on whole blood (initial qPCR range: 991-70,680 copies/mL). Notably, two children who transferred to another facility were negative for HAdV by RT-PCR when plasma was tested (instead of whole blood). Six children underwent liver biopsy showing varying degrees of hepatitis with no adenovirus detected on immunohistochemistry stains. Five children had HAdV type 41 confirmed. Three children presented or progressed to acute liver failure, two children were treated with cidofovir, and two underwent successful liver transplantation. No known epidemiologic links between patients were identified and all were from geographically distinct parts of Alabama. Conclusion HAdV is a potentially underrecognized cause of hepatitis. Whole blood specimens may be preferred over plasma for HAdV RT-PCR testing. HAdV type 41 was identified in all patients with typing results available. Improved type-based surveillance may help determine HAdV patterns of circulation and inform future diagnostic testing. Disclosures William Britt, MD, First Energy Corporation: Stocks/Bonds|Hookipa Pharma: Advisor/Consultant|Kroger Care: Stocks/Bonds|MDU Resources Group: Stocks/Bonds|PG&E Corporation: Stocks/Bonds.

The CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ETI) is a genetic mutation-targeted treatment in cystic fibrosis that results in profound improvements in clinical outcomes. Each of the compounds are substrates of CYP3A4/5, the cytochrome P450 enzyme family for which tacrolimus is also a substrate. The use of these compounds in an individual with a solid organ transplant has not been previously studied and there is potential for a drug interaction. In this report, we describe a pediatric liver transplant recipient with clinical decline related to cystic fibrosis who improved substantially with ETI, without significant impact on the systemic exposure of either ETI or tacrolimus.

INTRODUCTION: The pediatric obesity epidemic is associated with early development of hepatic macrosteatosis, a hallmark of nonalcoholic fatty liver disease, which is thought to be more rapidly progressive in children than adults. Macrosteatosis in adult allografts is associated with allograft loss, but this has not been examined in pediatric donors. METHODS: We studied all pediatric potential whole liver donors (2005–2018) who had a liver biopsy in the Scientific Registry for Transplant Recipients (SRTR) (n=862) and whose liver was transplanted (n=862). Macrosteatosis was abstracted from biopsy reports and compared to values in the SRTR standard analytic file. Recipients of macrosteatotic pediatric allografts were matched 1:1 to recipients of non-macrosteatotic pediatric allografts by propensity score matching on donor/recipient variables. All-cause allograft loss was estimated via Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: From 2005–2018, the proportion of pediatric donors (age≥2 years) with obesity increased (14.8% to 21.7%; P0.05). CONCLUSION: Obese pediatric liver donors have increased over time and were more likely to have hepatic macrosteatosis; however, pediatric macrosteatosis did not appear to adversely affect recipient outcomes.