Identification of key genes and infiltrating immune cells among acetaminophen-induced acute liver failure and HBV-associated acute liver failure.

BACKGROUND

Acute liver failure (ALF) is a life-threatening complication that is relatively uncommon. ALF causes severe hepatocyte damage and necrosis, which can lead to liver dysfunction and even multi-organ failure. A growing body of evidence suggests that immune cell infiltration and some abnormally expressed genes are associated with ALF development. However, in ALF, they have yet to be thoroughly investigated.

METHODS

The Gene Expression Omnibus (GEO) database was used to obtain microarray datasets such as GSE74000, GSE120652, GSE38941, and GSE14668, which were then examined via GEO2R to determine differentially expressed genes (DEGs) associated with ALF. Metascape was employed to annotate the underlined genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The mechanism of IGF1 in 2 different kinds of ALF including acetaminophen-induced ALF and hepatitis B virus (HBV)-induced ALF was studied using gene set enrichment analysis (GSEA). Next, immune cell infiltration was investigated and differentiated in ALF using CIBERSORT.

RESULTS

Six genes () were found to be abnormally expressed in the 2 distinct types of ALF i.e., acetaminophen-induced ALF and HBV-induced ALF. was identified as a hub gene in ALF and was found to be associated with several developmental cascades including immune responses, inflammatory responses, and intracellular calcium homeostasis. Additionally, the number of CD4 naive T cells, CD8 T cells, and follicular helper T cells was increased in acetaminophen-induced ALF, whereas the number of activated NK cells, resting NK cells, and plasma cells was increased in HBV-induced ALF.

CONCLUSIONS

The present study determined a potential molecular target, namely , in acetaminophen-induced ALF and HBV-induced ALF, which may provide novel insights into the pathophysiology and management of ALF. Concurrently, the putative immunological pathways have been found.