Shared gene signatures reveal metabolic dysfunction in liver cirrhosis and acute-on-chronic liver failure

Background and objectives

Chronic liver cirrhosis (LC) and acute-on-chronic liver failure (ACLF) are interconnected hepatic disorders associated with substantial morbidity and mortality. Despite their distinct clinical characteristics, both conditions share common pathogenic pathways that remain inadequately understood. This study aimed to identify shared gene signatures and elucidate underlying molecular mechanisms.

Methods

In this study, we employed Weighted Gene Co-Expression Network Analysis to explore transcriptomic data from the Gene Expression Omnibus for LC and ACLF.

Results

Key co-expression modules enriched with genes involved in glycolysis and gluconeogenesis pathways were identified, implicating metabolic dysfunction as a central feature in both conditions. Furthermore, microRNA analysis revealed that hsa-miR-122 and hsa-miR-194 play pivotal roles in regulating these metabolic pathways, potentially contributing to immune dysregulation.

Conclusions

Our transcriptomic analysis has uncovered a potential pathogenic association between glucose metabolism and both ACLF and LC. This association is mediated by miR-122 and miR-194, along with their corresponding signaling pathways. These findings highlight novel therapeutic targets that warrant further in-depth exploration.