Serum PreS1 antigen combined with vascular endothelial growth factor can identify low-level hepatitis B virus DNA replication in patients with hepatitis B e antigen-negative chronic infection.

BACKGROUND: Patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection exhibiting low-level viremia (HBV DNA 20-2000 IU/mL) represent a clinical "gray zone" with uncertain disease activity. Simple serologic markers are needed when high-sensitivity HBV DNA testing is unavailable. OBJECTIVE: To evaluate serum PreS1 antigen combined with vascular endothelial growth factor (VEGF) for identifying low-level HBV DNA replication in HBeAg-negative chronic HBV infection. METHODS: This single-center retrospective study enrolled 178 patients with HBeAg-negative chronic HBV infection (Xi'an No.1 Hospital, January-June 2025). Based on HBV DNA quantification, patients were classified into suppressed (< 20 IU/mL, n = 118) and low-level HBV DNA replication (20-2000 IU/mL, n = 60) groups. Serum PreS1 antigen (by enzyme-linked immunosorbent assay [ELISA]), and VEGF (by quantitative ELISA) were measured. Logistic regression and receiver operating characteristic (ROC) curves were used. RESULTS: The low-level HBV DNA replication group had higher PreS1 positivity (53.3% vs. 4.2%, P < 0.001) and higher VEGF levels (191.75 ± 64.15 vs. 123.36 ± 39.74 pg/mL, P < 0.001). PreS1 positivity (adjusted odds ratio [OR] = 37.209) and each one-standard-deviation increase in VEGF (adjusted OR = 4.596) were independent risk factors. Area under the ROC curve (AUC) for PreS1 alone was 0.745 (sensitivity 53.3%, specificity 95.8%); for VEGF alone, 0.812 (sensitivity 61.7%, specificity 91.5% at 172.32 pg/mL cutoff). The combined model achieved AUC 0.900 (sensitivity 80.0%, specificity 93.2% at probability cutoff 0.328). CONCLUSIONS: Serum PreS1 antigen combined with VEGF showed excellent diagnostic performance for identifying low-level HBV DNA replication in HBeAg-negative chronic HBV infection, offering a practical adjunct to high-sensitivity HBV DNA testing.