Serum CXCL16: A new predictor of liver inflammation in patients with chronic hepatitis B.

The prompt initiation of antiviral therapy is essential in patients with chronic hepatitis B (CHB), especially when severe liver inflammation is detected. However, transcutaneous liver puncture, the gold standard for assessing liver inflammation, is invasive and its widespread application is limited. Therefore, there is an urgent need for more non-invasive markers to predict liver inflammation. In our retrospective cross-sectional study, which included 120 CHB patients and 31 healthy subjects, we observed a significant increase in serum chemokine C-X-C-motif ligand 16 (CXCL16) in CHB patients compared to healthy controls (p < .001). Notably, patients with severe inflammation (Scheuer's grade G ≥ 3, n = 26) exhibited a substantial increase in serum CXCL16 compared to those with non-severe inflammation (Scheuer's grade G < 3, n = 96) [(median, IQR), 0.42 (0.24-0.71) ng/mL vs. 1.01 (0.25-2.09) ng/mL, p < .001]. Furthermore, we developed a predictive model that combined CXCL16 with platelet count (PLT), alanine aminotransferase (ALT) and albumin (ALB) to accurately predict liver inflammation in CHB patients. This model was more effective than ALT alone in predicting liver inflammation (AUC, 0.92 vs. 0.81, p = .015). Additionally, using an HBV-transduced mouse model, we demonstrated that blocking CXCL16 led to a reduction in liver inflammation and impaired infiltration and function of natural killer T (NKT) and natural killer (NK) cells. These findings suggest that CXCL16 is a promising non-invasive biomarker of liver inflammation in CHB patients and may play a role in inducing liver inflammation via a NKT and NK cell pathway.