Integrated metabolomics analysis identifies distinct amino acid signatures in chronic hepatitis B patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND

Chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexist and synergistically accelerate progression to end-stage liver disease. However, the metabolic differences distinguishing CHB alone from CHB with MASLD remain poorly defined.

METHODS

Serum samples from 47 CHB patients with or without MASLD were analyzed as a discovery set using widely targeted metabolomics. An independent validation set of 94 samples was subsequently examined with targeted metabolomics.

RESULTS

CHB patients with MASLD showed marked alterations in amino acid metabolism compared to those with CHB alone. Analysis revealed 206 significantly altered metabolites, among which amino acids represented the largest altered subgroup. Targeted quantification validated nine amino acids significantly upregulated in CHB-MASLD patients: leucine, tryptophan, phenylalanine, tyrosine, glutamic acid, alanine, histidine, lysine, and 2-aminoadipate. These 9 differential amino metabolites (9-DAM) robustly discriminated CHB with MASLD from CHB alone, achieving AUCs of 0.889 and 0.918 in the discovery and validation sets, respectively. The 9-DAM panel consistently outperformed controlled attenuation parameters (CAP) and correlated positively with CAP and liver stiffness measurements.

CONCLUSIONS

CHB patients with MASLD exhibit a distinct disruption of circulating amino acid metabolism, reflecting unique metabolomic signatures. These findings highlight promising biomarkers and the pathophysiological significance of this comorbidity.