NMR-based metabolomic signature: An important tool for the diagnosis and study of pathogenesis of autoimmune hepatitis

Abstract

Background & Aims: Metabolomics are used to predict, diagnose, and monitor metabolic disorders but altered metabolomic signature has also been reported in diverse diseases, including autoimmune disorders. However, the metabolomic profile in autoimmune hepatitis (AIH), has not been investigated in depth. Therefore, we investigated the metabolomic signature of AIH and its significance as a diagnostic and pathogenetic tool. Approach & Results: Metabolites in plasma samples from 50 AIH patients at diagnosis, 43 healthy controls (HC), 72 patients with primary biliary cholangitis (PBC), 26 patients with metabolic dysfunction-associated liver disease (MASLD) and 101 patients with chronic viral hepatitis (CVH) were determined by 1H-NMR spectroscopy. Fifty-two metabolites were quantified, and metabolic pathway analysis was performed. Multivariate analysis revealed that AIH could be differentiated from HC and each of the disease controls (p<0.001). 15 metabolites differentiated AIH from disease controls (PBC+CVH+MASLD) (95% sensitivity and 92% specificity). Ten distinct metabolic pathways were altered in AIH compared to disease controls. The metabolic pathway of branched-chain amino acids (BCAAs) (lower valine, leucine and isoleucine levels and their catabolic intermediates in PBC), methionine (lower methionine, 2-aminobutyrate and 2-hydroxybutyrate levels in PBC), alanine-aspartate-glutamate (lower metabolites in PBC) and that of metabolites associated with gut microbiota (lower choline, betaine, and dimethylamine levels in PBC) were significantly different between AIH and PBC (p<0.01). Conclusions: 1H-NMR spectroscopy could be a promising novel tool to diagnose and study AIH pathogenesis as there is no need of much sample handling, is highly reproducible with high sensitivity and specificity and low cost.