Cuproptosis‐Related Genes in Immune Infiltration and Diagnosis in Hepatitis B Virus‐Related Acute Liver Failure

ABSTRACT Hepatitis B virus (HBV) infection poses a significant challenge to global health, particularly in developing countries such as China, where HBV‐related acute liver failure (HBV‐ALF) is a prominent cause of acute liver failure. This study investigated the effect of cuproptosis, a recently identified form of cell death, on immune infiltration in HBV‐ALF. We mined the gene expression data of HBV‐ALF from the Gene Expression Omnibus database. Through enrichment analysis of differentially expressed genes (DEGs), pathways related to the response to metal/copper ions and the acute inflammatory response were found to be enriched. We subsequently found that HBV‐ALF tissues contained more copper ions and conducted an intersection analysis of DEGs and cuproptosis‐related genes (CRGs), which resulted in the identification of 7 core cuproptosis‐related DEGs (CR‐DEGs) for further investigation with a diagnostic model. Immune infiltration analysis and unsupervised clustering analysis revealed distinct patterns in HBV‐ALF and the possibility of crosstalk between ferroptosis and cuproptosis. Furthermore, we identified 17 transcription factors, 90 miRNAs, and 15 drugs that might interact with the 7 CR‐DEGs. To validate our findings and their clinical significance, we verified the diagnostic value and immune infiltration patterns of the 7 CR‐DEGs in both the testing dataset, cell line, and clinical samples. In conclusion, our findings indicated that these 7 CR‐DEGs demonstrate promising diagnostic value and may represent viable therapeutic targets for individuals with HBV‐ALF.