Systematic review on genetic polymorphisms associated with idiosyncratic drug-induced liver injury (iDILI): iDILInet...

Idiosyncratic drug-induced liver injury (iDILI) is a rare, dose-independent and unpredictable adverse reaction occurring at therapeutic drug exposure, and it presents a significant challenge for drug development and patient safety. Despite extensive research, genetic susceptibility to iDILI remains poorly understood. We conducted a comprehensive systematic study of 139 human genetic studies to identify and characterize genetic polymorphisms associated with increased risk or protection against iDILI. Our study included candidate gene studies and genome-wide association studies (GWAS), encompassing 83 risk and 25 protective genes, with NAT2, HLA-B, and SLCO1B1 among the most frequently reported. We performed functional enrichment analyses using KEGG and Gene Ontology, revealing key biological pathways related to immune response, xenobiotic metabolism, and bile secretion. To enhance data accessibility and interpretation, we developed iDILInet, a publicly available web application that enables interactive exploration and network-based visualization of iDILI-associated gene-variant-drug relationships, enriched with liver-specific expression data from the Human Protein Atlas (HPA). Our work provides a novel integrative resource that supports ongoing efforts in precision medicine and pharmacogenomics and represents a significant advancement in implementing living systematic reviews in toxicogenomics.