CXCL16 gene promoter methylation is associated with inflammation in patients with chronic hepatitis B

Hepatitis B virus (HBV) infection causes persistent hepatic inflammation, and chemokine CXCL16 serves as a key mediator in liver injury, but its epigenetic regulation in chronic hepatitis B (CHB) remains unclear. This study enrolled 217 CHB patients (113 HBeAg‑positive, 104 HBeAg‑negative) and 27 healthy controls to investigate CXCL16 promoter methylation, mRNA and protein expression, as well as their correlations with inflammatory indices and liver injury markers. The results showed that CXCL16 promoter methylation was significantly lower, while CXCL16 mRNA and serum levels were markedly higher in CHB patients, especially in HBeAg‑positive cases. CXCL16 promoter methylation was negatively correlated with CXCL16 expression, HBeAg status, ALT, AST, TNF‑α and IL‑1β levels. ROC analysis demonstrated that CXCL16 promoter methylation had favorable discriminative capacity for HBeAg-positive status (AUC = 0.749), which, together with its significant correlations with inflammatory markers, suggests its potential as a complementary indicator for identifying CHB patients with higher inflammatory burden. In conclusion, CXCL16 promoter hypomethylation is closely associated with elevated CXCL16 expression and exacerbated hepatic inflammation in CHB patients, and may serve as a potential non‑invasive biomarker for assessing CHB‑related liver inflammation. These findings enrich the epigenetic mechanism underlying HBV‑related hepatic inflammation and provide a novel target which is CXCL16 for clinical evaluation and intervention.