RNA-Sequencing Analysis Identifies Etiology Specific Transcriptional Signatures in Neonatal Acute Liver Failure

Samantha A. Saul, Catherine A. Chapin, Padmini Malladi, Hector Melin-Aldana, Joshua B. Wechsler, Estella M Alonso, Sarah Ann Taylor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)205-212.e2
Journaljournal of pediatrics
Volume253
DOIs
StatePublished - Feb 2023

Keywords

  • ductular reaction
  • gestational alloimmune liver disease (GALD)
  • hepatic regeneration
  • liver fibrosis
  • pediatric acute liver failure

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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