Abstract
OBJECTIVE: To assess hepatic transcriptional signatures in infants with gestational alloimmune liver disease (GALD) compared with other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF. STUDY DESIGN: Neonates with ALF (international normalized ratio ≥2 within 30 days of life) and deceased neonates without liver disease (<30 days of age) with available liver tissue between 2010 and 2021 were identified at ann & robert h. lurie children's hospital of chicago. clinical information, liver histology, and data from rna-sequencing analysis was compared between neonates with gald, non-gald etiologies of neonatal alf, and nondiseased neonatal liver. results: quantification of trichrome staining showed an increase in fibrosis in patients with gald vs those with non-gald neonatal alf (p =" .012);" however, quantification of α-cytokeratin 19-positive ductules did not differ between groups (p =" .244)." gene set enrichment analysis of rna-sequencing data identified the pathways of complement activation, fibrosis, and organogenesis to be upregulated in patients with gald with alf. in contrast, patients with non-gald causes of neonatal alf had increased gene expression for interferon-driven immune pathways. individual genes upregulated in gald included matrix metallopeptidase 7, hepatocyte growth factor, and chemokine ligand 14. conclusions: we have identified distinct pathways that are significantly upregulated in patients with gald and potential disease-specific diagnostic biomarkers. future studies will aim to validate these findings and help identify gald-specific diagnostic biomarkers to improve diagnostic accuracy and reduce gald-associated patient mortality.>30 days>