Association Between EBV Lytic Replication and Liver Injury in Patients With HBeAg‐Negative Chronic HBV Infection

The present study aims to characterize the impact of Epstein-Barr virus (EBV) lytic replication on liver disease in patients with chronic hepatitis B virus (HBV) infection. We retrospectively enrolled 261 patients with HBeAg-negative chronic HBV infection who were admitted to Zhongnan Hospital between 2019 and 2025. Plasma levels of HBV-DNA, EBV-DNA, and liver function parameters were collected. Patients were grouped based on their viral DNA status, and the association between viral DNA status and liver function was evaluated. Compared to the HBV-DNA-negative group, HBV-DNA-positivity was significantly associated with aggravated hepatic injury, as evidenced by elevated ALT, AST, lymphocyte count, and fibrosis scores (APRI and FIB-4). Notably, regardless of HBV-DNA status or the stage of liver disease (CHB or LC), EBV-DNA-positivity was consistently associated with significantly lower plasma albumin (Alb) levels and albumin-to-globulin (A/G) ratio compared to EBV-DNA-negative patients. The reduction in the A/G ratio was attributable to decreased Alb levels rather than to elevated globulin (Glb) levels. These results suggest that EBV lytic replication was associated with hypoalbuminemia in this study. Circulating EBV-DNA status holds promise as a potential biomarker for monitoring disease progression, or assessing disease severity in patients with chronic HBV infection.