Glutathione species and metabolomic prints in subjects with liver disease as biological markers for the early detection of hepatocellular carcinoma (HCC)

Abstract

The incidence of liver disease is increasing mainly as a result of viral infections and obesity. The present study explored the role of glutathione sp. and metabolic prints in the progression of liver dysfunction and early detection of HCC. Three subsets of subjects were enrolled on IRB approved protocols: healthy subjects (n = 20), patients with end stge liver disease and diverse MELD score (n = 99) and patients after LTx (n = 29). Treated plasma was analyzed by LC/MS-MS and identification of metabolites was performed using metabolomic libraries. Glutathione sp. synthesis rate was calculated by isotopomer analyzes of 2H-labelled compounds. Parametric analytical tests were performed to compare groups and Principal Component Analyzes (PCA) were implemented to explain differences in metabolic prints. There was a significant difference in glutathione sp and Tier 1, 2, and 3 (3, 21 and 72 compounds) metabolic profiles from patients with ESLD when compared to healthy subjects and patients after LTx (p < 0.05). Patients with ESLD and HCC (+) had a significant different profile when compared to patients with ESLD and HCC (-, p < 0.05). Patients stratified by MELD score or by etiology showed a different metabolic profile. Patients with ESLD had a significant decreased in GSH synthesis and increased GSSG production when compared to healthy subjects and to patients after LTx (p < 0.05). Glutathione sp and metabolic prints may defined liver disease progression and served as surrogate for the early detection of HCC in patients with ESLD. Patients after LTx remained with significant metabolic disturbances no reflected in standard liver function tests.