Metabolic differences among patients with alcohol-related liver disease using targeted and untargeted metabolomics techniques

Abstract Background Alcoholic liver disease (ALD) represents a significant global public health challenge. Aims This study aims to investigate the metabolic characteristics of ALD through metabolomics technology. Methods This non-interventional, observational case-control study included 29 healthy individuals and 105 ALD patients treated at a Chinese hospital from August 2023 to March 2024. Fasting venous blood samples were collected from all subjects for non-targeted or amino acid targeted metabolomics analysis. Results A combination of univariate and multivariate statistical analyses identified 37 differentially expressed metabolites (DEMs) through non-targeted metabolomics with amino acid metabolism being the most significantly altered pathway. Further targeted analysis confirmed that levels of Glu, Pro, and Orn significantly increased with disease progression (all P < 0.05), whereas Cit and Arg levels significantly decreased (all P < 0.005). Pro and Glu exhibited significant diagnostic potential for ALD patients (OR = 1.013 and 1.022, P = 0.029 and 0.002, respectively). Pro demonstrated the strongest discriminatory ability in distinguishing alcoholic hepatitis (AH) from alcoholic cirrhosis (ALC) (AUC = 0.764). Spearman correlation analysis revealed that Cit was negatively correlated with AST, GGT, and TG levels. Conclusions Serum levels of five DEMs (Glu, Pro, Orn, Cit, and Arg) are closely linked to ALD-related metabolic dysregulation; they serve as potential indicators of ALD progression and provide valuable insights for the clinical staging and targeted intervention of ALD.