Elevated C18:1-acylcarnitine is associated with a higher fibrosis-4 index through inflammation mediation: A cross-sectional study.

As a major response to chronic hepatic injury, liver fibrosis presents a growing global health challenge. However, its association with metabolomic signatures remains unclear. In this study of 492 patients, we evaluated associations between 30 metabolites and liver fibrosis, which was assessed non-invasively using the fibrosis-4 (FIB-4) index. We hypothesized that metabolic changes promote fibrosis partly through inflammatory pathways. Propensity score matching, Spearman's correlation, binary logistic regression, and restricted cubic spline analyses were employed to identify key metabolites associated with fibrosis risk. Mediation analysis further investigated inflammatory biomarkers as potential mediators. Elevated plasma glutamine [odds ratio (OR) = 1.02, 95% confidence interval (CI) = 1.00-1.04], log-transformed C18:1-acylcarnitine (OR = 2.59, 95% CI = 1.12-5.95), and betaine (OR = 1.20, 95% CI = 1.06-1.36) were strongly related to increased liver fibrosis risks, whereas lower alanine concentration (OR = 0.97, 95% CI = 0.95-1.00) correlated with decreased risks. Several metabolites [specifically alanine, log-transformed C18:1-acylcarnitine, and betaine (all P overall < .05, P non-linear > .05)] showed linear dose-response relationships with fibrosis risk. Inflammatory factors, notably the neutrophil-percentage-to-albumin ratio (mediation proportion = 49.7%, P = .01), and metabolites including glutamic acid (mediation proportion = -23.4%, P = .47) and betaine (mediation proportion = 48.3%, P = .03), significantly mediated the relationship between C18:1-acylcarnitine and liver fibrosis. Our findings suggest that dysregulation of key metabolomic biomarkers may interact with inflammatory responses, thereby accelerating liver fibrosis, and underscore the modulating roles of inflammation in the progression of liver fibrosis.