Background: Trace elements play crucial roles in liver health and immune function, yet their alterations in chronic hepatitis B virus (HBV) infection remain poorly characterized, particularly in resource-limited settings. The copper-to-zinc ratio has emerged as a potential biomarker for liver disease severity, but its relationship with viral replication in chronic HBV infection has not been systematically evaluated.

Objective: To characterize trace element profiles in chronic HBV patients and investigate the clinical significance of copper-to-zinc ratio as a disease activity marker correlating with viral load and liver inflammation.

Methods: A cross-sectional study was conducted among 300 chronic HBV patients in Rajasthan, India. Serum copper and zinc levels were measured using atomic absorption spectroscopy. The copper-to-zinc ratio was calculated and correlated with HBV DNA levels, liver function tests, and clinical parameters. Multivariate analysis was performed to identify independent predictors of disease activity.

Results: Zinc deficiency was present in 156 patients (52.0%), while 67 patients (22.3%) had elevated copper levels. The copper-to-zinc ratio was elevated (>1.5) in 189 patients (63.0%). The copper-to-zinc ratio showed the strongest correlation with HBV DNA levels among all measured parameters (r = 0.467, p < 0.001). Zinc levels correlated negatively with viral load (r = -0.398, p < 0.001), while copper levels showed positive correlation (r = 0.356, p < 0.001). HBeAg-positive and treatment-naïve patients had significantly worse trace element profiles. The copper-to-zinc ratio demonstrated superior diagnostic performance for identifying high viral loads (AUC = 0.751) compared to individual element measurements.