Interferon therapy for chronic hepatitis B virus infection affects nucleoside metabolism: a metabolomics study.

Pegylated interferon alfa (pegIFN-α) is one of the main therapeutic strategies for chronic hepatitis B (CHB) infection. Although interferon-based treatment strategies have great potential in combating CHB, they have significant side effects, and many patients do not respond. In this study, nontargeted metabolomics was performed to investigate the effects of interferon therapy on metabolites and their correlations with clinical indicators. Each group of 20 patients received PEG-IFN alfa-2b for 0, 1, 3, or 6 months. At the end of the IFN-α treatment, patient serum samples were processed for clinical, biological, and metabolomic analyses. The results revealed that in all four groups, the most affected metabolic pathways were ABC transporter, caffeine metabolism, and protein digestion and absorption. Notably, among the top 8 differentially abundant metabolites with high ROC AUC values (≥ 0.95), three were related to pyrimidine nucleoside metabolites (cytidine, 3-methyluridine and ribothymidine), indicating the pivotal role of altered nucleoside metabolism in HBV infection and suggesting that IFN-α treatment might partially correct this dysregulation. The top 20 metabolites were strongly associated with clinical indicators, with significant differences after IFN-α treatment, and may serve as promising biomarkers for monitoring HBV progression and the therapeutic effect of IFN-α treatment for chronic HBV infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04126-0.