Untargeted Plasma Metabolomics Reveals Extensive Metabolic Alterations Among Treatment-Naive Human Immunodeficiency Virus/Hepatitis C Virus Co-Infected Patients with Liver Disease Progression

Abstract

Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may induce metabolic disorders and cause liver complications. Therefore, we aim to analyze the metabolite differences among treatment-naive HIV/HCV co-infected patients with versus without liver disease progression (LDP) and HIV mono-infected patients. A cross-sectional study was conducted in 65 HIV/HCV co-infected patients (22 with LDP and 43 without) and 65 HIV mono-infected patients in Dehong prefecture of Yunnan province, China. Plasma metabolomics were measured by gas chromatography–mass spectrometry (MS) and liquid chromatography–MS. Discrimination analysis, pathway enrichment analysis, generalized linear model with binomial distribution, and area under the receiver-operating characteristic curve (AUC) were conducted to identify bilateral differences in metabolites and pathways in different comparison groups. A total of 10,831 with 673 named and 10,158 unnamed metabolites were detected. Compared with HIV/HCV co-infected patients without LDP, phenylalanine, tyrosine, and tryptophan biosynthesis pathway with the increased level of tyrosine were significantly altered among HIV/HCV co-infected patients with LDP. Compared with HIV mono-infected patients, the decreased level of glutamine and increased levels of glutamic acid, arachidonic acid, and its derivatives were identified among HIV/HCV co-infected patients. Metabolite panels adjusted for baseline information had a higher accuracy than baseline model (without metabolite information) in distinguishing HIV/HCV co-infected patients with versus without LDP (AUC 0.951 vs. 0.849, p = .027) and HIV/HCV co-infected patients from HIV mono-infected patients (AUC 0.889 vs. 0.766, p < .001). A novel set of metabolites were found to discriminate HIV/HCV co-infected patients with versus without LDP, and from HIV mono-infected patients, which may have mechanistic and interventional implications.