Plasma Lipid Metabolites Differentiate Metabolic From Viral Chronic Liver Disease

Lipid metabolism is altered in human immunodeficiency virus (HIV) infection and chronic liver diseases, but common and unique pathways have not been elucidated, limiting prevention and treatment strategies. The aim of this study was to discover lipid metabolite signatures for persons with HIV (PWH), PWH with HCV coinfection (PWH-HCV), and individuals with metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD, MASH).

Plasma metabolite profiling was performed in adult participants in 5 cohorts from a single center: PWH (n = 50), PWH-HCV (n = 50), HIV-negative biopsy-proven MASLD (n = 46), and MASH (n = 50), and controls without HIV or chronic liver disease (n = 29). Plasma metabolites were assessed using Biocrates Q500, bile acid, and oxylipin assays. Latent factor analysis along with unadjusted and adjusted logistic regression models were performed. Significance was defined as P value < .05 and false discovery rate < 0.10.

Compared to controls, 457 of 816 measured metabolites were detected at different levels in PWH, 352 in PWH-HCV, 466 in MASLD, and 487 in MASH. Triglycerides and oxylipins were increased across disease states, but to a higher degree in PWH. PWH-HCV had a distinct metabolite signature with decreased ceramides and sphingomyelins. Levels of bile acid, amino acid, and fatty acid metabolites also differentiated cohorts.

Lipid metabolites demonstrated pathways common to, and unique to, HIV, HCV, and MASLD. Further studies will hopefully reveal the pathogenic role of these metabolites in liver disease severity, particularly in PWH with steatotic liver disease.