Paired liver-tissue metabolomics and proteomics delineate the perilesional microenvironment of hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis (HAE) is a chronic infiltrative parasitic disease, yet the molecular organization of the human host-parasite interface remains incompletely resolved. This study aimed to characterize metabolic and proteomic differences between close liver tissue (CLT) and distal liver tissue (DLT) in HAE. Untargeted LC-MS/MS metabolomics and data-independent acquisition proteomics were performed on paired CLT and DLT samples from 22 patients with HAE. Differential analysis, weighted gene co-expression network analysis, DIABLO-based cross-omics integration, and pathway enrichment were used to identify candidate molecular signatures. We identified 213 differentially expressed metabolites, of which 127 were increased and 86 were decreased in CLT, together with 164 differentially expressed proteins, of which 125 were increased and 39 were decreased. Independent analytical layers highlighted candidate metabolic and host-protein signatures involving aromatic amino acid metabolism, complement-associated regulation, cytoskeletal remodeling, cellular adhesion, and phosphatidylinositol-related annotations. Paired-tissue multi-omics identified candidate metabolic and host-protein signatures associated with CLT relative to DLT, including aromatic amino acid metabolism, complement-associated regulation, and RHO-family GTPase-associated cytoskeletal pathways. In the absence of an external cohort or orthogonal experimental validation, these exploratory findings require independent validation before causal or clinical inferences can be made.