Dysregulation of the IL-6/hepcidin axis in Egyptian systemic lupus erythematosus patients: associations with anemia of inflammation and liver fibrosis

Abstract Background This study was motivated by the high prevalence of anemia of inflammation (AI) in systemic lupus erythematosus (SLE) and the poorly explored potential link between the underlying inflammatory drive and hepatic complications. The IL-6/hepcidin axis is a key pathway in AI, but its role in concurrent liver pathology is not well defined. The aim of this study was to investigate the relationship between the IL-6/hepcidin axis, AI, and hepatic fibrosis in Egyptian SLE patients. Methods 102 SLE patients and 25 healthy controls were enrolled in the study. Serum levels of IL-6, hepcidin, IL-33, liver enzymes (AST, ALT) as markers of hepatocellular injury, and other clinical parameters were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and liver fibrosis was evaluated non-invasively using the AST to Platelet Ratio Index (APRI). Results Patients were classified into those with and without AI. AI was present in 91.2% of patients. The SLE cohort showed significantly elevated IL-6, hepcidin, and liver enzymes compared to controls. APRI-defined hepatic fibrosis (including cirrhosis) was detected in 30 patients (29.41%), all within the AI subgroup. Strong positive correlations were found between hepcidin levels and SLEDAI (r = 0.46; p < 0.001), AST (r = 0.777; p < 0.001), and ALT (r = 0.747; p < 0.001). However, neither hepcidin (AUC = 0.566, 95% CI: 0.449–0.683, p = 0.267) nor IL-6 (AUC = 0.541, 95% CI: 0.416–0.665, p = 0.516) demonstrated clinically useful diagnostic accuracy for detecting APRI-defined liver fibrosis. Conclusions Chronic IL-6-driven inflammation in SLE propels a dual pathology; inducing hepcidin-mediated AI and being associated with liver damage. Hepcidin and IL-6 are correlates rather than causes of fibrosis. APRI remains a reliable non-invasive tool for identifying patients at risk of hepatic fibrosis in SLE, particularly those with AI, and should be incorporated into routine clinical assessment. Graphical Abstract