https://pubmed.ncbi.nlm.nih.gov/36195310/ Acute liver failure

J Pediatr. 2022 Oct 1;S0022-3476(22)00866-6.
doi: 10.1016/j.jpeds.2022.09.044.Online ahead of print.

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

Samantha A Saul 1, Catherine A Chapin 1, Padmini Malladi 1, Hector Melin-Aldana 1, Joshua B Wechsler 1, Estella M Alonso 1, Sarah A Taylor 2
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PMID: 36195310

DOI: 10.1016/j.jpeds.2022.09.044
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Abstract

Objective: To assess hepatic transcriptional signatures in infants with GALD compared other etiologies of neonatal acute liver failure (ALF) and older pediatric patients with ALF.

Study design: Neonates with ALF (INR > 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 Lurie Children's Hospital of Chicago. Clinical information, liver histology, and data from RNA-sequencing analysis was compared between neonates with gestational alloimmune liver disease (GALD), non-GALD etiologies of neonatal ALF, and non-diseased neonatal liver.

Results: Quantification of trichrome staining showed an increase in fibrosis in patients with GALD versus those with non-GALD neonatal ALF (p = 0.012), however, quantification of CK-19 positive ductules did not differ between groups (p = 0.244). 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 (MMP7), hepatocyte growth factor (HGF), and chemokine ligand 14 (CXCL14).

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.