ArticleFrontiers in immunology2026
Plasma gamma-glutamylglycine predicts the seroconversion of hepatitis B e antigen in patients with chronic hepatitis B.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The seroconversion of hepatitis B e antigen (HBeAg) remains difficult to be completely obtained in the treatment of hepatitis B. This study aimed to characterize the metabolic signatures of HBeAg-positive patients and identify key metabolites associated with HBeAg seroconversion. Methods: Untargeted metabolomic analysis was conducted to investigate the plasma metabolic profiles of HBeAg-positive (n=54) and negative (n=33) patients. Subgroup analyses were performed in patients with persistent HBeAg<20IU/ml level (n=33) versus those with HBeAg-negative (n=33) and patients with immune tolerant (n=8) versus immune active phases (n=7). Targeted metabolomic analysis was used to validate specific amino acids in an external cohort (n=90). The biological effects of gamma-glutamylglycine were examined by Results: Compared with patients who achieved HBeAg seroconversion, HBeAg-positive patients exhibited distinct metabolic profiles, with 227 differential metabolites (133 downregulated and 94 upregulated, P<0.05). KEGG pathway enrichment analysis revealed downregulated tryptophan, pyruvate, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism and upregulated arginine biosynthesis, and cysteine and methionine metabolism in HBeAg-positive patients (P<0.01). Gamma-glutamylglycine and Na-L-glutamyl-aspartic acid were significantly upregulated in HBeAg-positive patients by both untargeted and targeted metabolomic analysis (P<0.05). Furthermore, a predictive model integrating plasma gamma-glutamylglycine accurately identified HBeAg seroconversion in both developing (AUC = 0.857, 95% CI: 0.765-0.923) and external (AUC = 0.780, 95% CI: 0.680-0.861) cohorts. Conclusions: Altered amino acid metabolism is a predominant metabolic feature of HBeAg-positive patients and plasma levels of gamma-glutamylglycine are negatively associated with HBeAg seroconversion.
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