RNA-Sequencing Analysis Identifies Etiology Specific Transcriptional Signatures in Neonatal Acute Liver Failure.
J Pediatr
; 253: 205-212.e2, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36195310
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. STUDYDESIGN:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Falência Hepática Aguda
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Child
/
Humans
/
Infant
/
Newborn
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article