Integrative Analysis of Molecular Interactions and Repurposable Drugs in Primary Biliary Cholangitis

Introduction: Primary Biliary Cholangitis (PBC) is an autoimmune liver disease characterized by chronic destruction of intrahepatic bile ducts, leading to fibrosis and eventual liver failure. Current first-line treatments, including ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), provide insufficient therapeutic benefit for a substantial proportion of patients. Integrative systems-level analyses of multi-omic data enable the identification of potential therapeutic targets and the repurposing of existing drugs. Methods: A total of 214 human genes associated with PBC were retrieved from NCBI Gene and DisGeNET databases. Protein-protein interaction (PPI) networks were constructed using STRING and subsequently analyzed for hub genes and network clusters using Cytoscape. Pathway enrichment analysis was performed using Reactome, and drug-gene associations were evaluated using the DSigDB database. Selected drug-target interactions were further assessed using experimentally validated binding data from BindingDB and molecular docking results generated by SwissDock. Results: The network analysis produced 187 nodes which connected through 1,645 edges. Hub gene analysis highlighted TP53, IL6, CXCL8, STAT3, IFNG, JUN, and CDKN1A as central regulators of immune and apoptotic signaling pathways. The Reactome analysis showed that interleukin and TP53-mediated pathways achieved statistical significance at an FDR value of less than 0.05. The FDA has approved six compounds for medical use including Simvastatin and Budesonide and Tocilizumab and N-acetylcysteine and PD98059 and Vorinostat which demonstrate supportive experimental or computational evidence of target engagement. Conclusion: This integrative network-based framework identified central molecular regulators and repurposable drugs for PBC. Further experimental and clinical studies are required to determine the therapeutic potential of these candidates in autoimmune liver disease.