Hepatitis B Virus RNA Levels and Clinical Characteristics of Persistent Viremia in HBsAg-positive Patients undergoing Nucleos(t)ide Analog

Aim This study aimed to analyze serum HBV RNA levels in HBsAg-positive patients with persistent viremia undergoing nucleos(t)ide analog (NAs) therapy for over 48 weeks and to examine the clinical characteristics of HBV RNA-positive patients. Methods In this cross-sectional study, 277 patients with complete virological response (CVR) and 277 patients with persistent viral positivity (PV) were included, with confounders balanced using 1:1 propensity score matching (PSM). Serum HBV RNA levels were quantified using a PCR-fluorescent probe assay, with a lower limit of quantification of 100 copies/mL. Patients in the PV group were classified into RNA-negative (<100 copies/mL) and RNA-positive (≥100 copies/mL) subgroups based on RNA levels. Results The HBV RNA-positive rate was significantly higher in the PV group than in the CVR group (P < 0.001). Multivariable regression analysis identified ALT, AST, HBsAg level, HBeAb status, and HBV RNA status as independent predictors of HBV DNA positivity. ALT levels were significantly higher in HBV RNA-positive patients, and the prevalence of cirrhosis and splenomegaly was notably higher in the RNA-positive group (P < 0.05), suggesting more severe liver damage. HBV RNA status was positively associated with HBsAg, HBeAg, and HBV DNA positivity. Conclusion HBV RNA status is an important marker of viral replication activity and liver injury, particularly in PV patients. Monitoring HBV RNA status as a non-invasive biomarker may help assess disease progression and inform patient management.