Bioinformatics Analysis of Persistent Dysregulated Expression of Genes Involved in HCV-Induced Neurological Disorders and Liver Injuries After DAA Treatment Through Weighted Gene Co-Expression Network Analysis.

Background and Aims: The molecular processes involved in the progression of neuropsychiatric and liver disorders in some patients who have achieved sustained virologic response after successful DAA treatment are still unclear. To understand these processes, we investigated alterations in the transcription patterns of genes associated with neural and immune functions after DAA therapy. Methods: A total of six microarray gene expression datasets related to patients who had received DAA treatment were downloaded from the Gene Expression Omnibus. Three groups comprising pretreatment and posttreatment CHC patients, as well as healthy subjects, were considered for the analysis. A weighted gene co-expression network analysis was then performed to identify the gene groups (modules) implicated in chronic hepatitis C before and after DAA treatment. Differential gene expression (DEG) analysis and protein-protein interaction network (PPIN) analysis were then used to determine the major dysregulated genes before and after treatment. Results: The common genes identified between the DEGs and selected modules, as well as further PPIN analysis, revealed the non-normalization of novel neural-related genes, including IRF3, FYN, CFL1, TGFβ1, DPYSL2, CDK5, and GIT1, as well as novel immune-related genes, including IκBα, CD14, IL-1β, IRAK1, TBK1, and CEBPB, after DAA treatment. Conclusions: Our findings suggest that DAA treatment does not lead to the normalization of gene transcription patterns in CHC patients up to 6 months after HCV clearance. The non-normalization of neuronal and immune gene expression, along with subsequent changes in the activity of related pathways, may contribute to the persistence or progression of HCV-induced neuropsychiatric disorders and liver injuries after DAA treatment. The identified genes and their altered expression patterns provide novel insights into potential molecular mechanisms underlying disease progression following successful DAA therapy. Furthermore, these genes may serve as candidate biomarkers for monitoring disease progression or as potential targets for therapeutic intervention.