Metabonomics screening of serum identifies pyroglutamate as a diagnostic biomarker for nonalcoholic steatohepatitis

• Published in: Clinica chimica acta Vol. 473; pp. 89 - 95
• Main Authors: Qi, Suwen, Xu, Depeng, Li, Qiaoliang, Xie, Ni, Xia, Jun, Huo, Qin, Li, Pu, Chen, Qiwen, Huang, Si
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2017
• Subjects: Biomarkers - blood; Female; Humans; Male; Metabolic profiling; Metabolomics; Middle Aged; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - metabolism; Nonalcoholic steatohepatitis; Pyroglutamate; Pyrrolidonecarboxylic Acid - blood; Simple steatosis; Metabolic profiling; Simple steatosis; Pyroglutamate; Nonalcoholic steatohepatitis; Non-alcoholic fatty liver disease
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2017.08.022

A key step in managing non-alcoholic fatty liver disease (NAFLD) is to differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis (SS). Serum samples were collected from three groups: NASH patients (N=21), SS patients (N=38) and healthy controls (N=31). High performance liquid chromatography-mass spectrometry (HPLC-MS) was used to analyse the metabolic profile of the serum samples. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) to identify novel metabolites. The potential biomarkers were quantitatively determined and their diagnostic power was further validated. A total of 56 metabolites were capable of distinguishing NASH from SS samples based on the OPLS-DA model. Pyroglutamate was found to be the most promising factor in distinguishing the NASH from SS groups. With an optimal cut-off value of 4.82mmol/L, the sensitivity and specificity of the diagnosis of NASH were 72% and 85%, respectively. The area under the receiver operating characteristic (AUROC) of the pyroglutamate levels of NASH versus SS patients was more than those of tumor necrosis factor-α, adiponectin and interleukin-8. These data suggest that pyroglutamate may be a new and useful biomarker for the diagnosis of NASH. •HPLC-MS was used to analyse the metabolic profile of the serum samples from patients with NASH.•Uracil, α-linolenic acid, glutamate, l-glutamine and pyroglutamate, were identified as prominent factors for NASH.•Pyroglutamate distinguished the NASH from SS groups with the sensitivity and specificity 72% and 85%, respectively.•The potential diagnostic power of pyroglutamate was superior to factor-α (TNF-α), adiponectin and interleukin-8 (IL-8).