BMI mediates the association of CALLY index with liver steatosis and fibrosis.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel marker for systemic inflammation, immunity, and nutritional health. However, its association with hepatic steatosis and liver fibrosis, and how body mass index (BMI) influences these associations, are yet unknown. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Hepatic steatosis and liver fibrosis were assessed by vibration-controlled transient elastography (VCTE). Multivariable linear regression and mediation analysis were conducted to evaluate the relationships between the CALLY index and CAP/LSM, and to quantify the mediating effect of BMI. The total number of participants was 6,404. The CALLY index was significantly inversely associated with hepatic steatosis (CAP, β = -0.72; 95% CI: -0.95 to -0.48) and liver fibrosis (LSM, β = -0.02; 95% CI: -0.04 to -0.01) before adjustment for BMI. In the final adjusted model, individuals in the third tertile of the CALLY index exhibited significantly lower CAP (β = -14.66; 95% CI: -20.73 to -8.60) and LSM levels (β = -0.65; 95% CI: -1.25 to -0.06) than the lowest tertile. Mediation analysis revealed that BMI accounted for 73.40% of the association between the CALLY index and CAP, and 93.33% of the association with LSM. Subgroup analyses showed stronger connections between the CALLY index and CAP/LSM in participants with obesity (BMI ≥ 30 kg/m²). While an inverse association between the CALLY index and hepatic steatosis/liver fibrosis was observed, this relationship was largely mediated by BMI, indicating that CALLY may reflect obesity-related mechanisms rather than exerting an independent effect. These results need to be confirmed by additional validation in longitudinal cohort research.