To investigate the factors and the virological significance of serum hepatitis B virus (HBV) pgRNA after long-term antiviral therapy with nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB) patients.
In total, 51 treatment-naïve CHB patients were included in the study. Clinical data were collected at baseline and after 5 years and at year 10 of antiviral treatment. Serum HBV pregenomic RNA (pgRNA) status of 51 patients was detected at year 5.
After 5 years of antiviral treatment, 45.10% of the patients were still positive for HBV pgRNA. There were significant differences in baseline hepatitis B e antigen (HBeAg) status, HBV DNA load and hepatitis B surface antigen (HBsAg) levels between patients positive and negative for HBV pgRNA at year 5. Serum HBV pgRNA status and serum HBV DNA load were correlated even after 5 years of treatment (r = 0.347, p = 0.013). Being HBV pgRNA positive at year 5 was an independent risk factor for sustainedly undetectable HBV DNA after 10 years of antiviral treatment (OR: 13.638, 95% CI: 1.32-140.81, p = 0.028). Furthermore, HBV pgRNA status at year 5 was associated with HBV DNA reappearance at year 10 (p = 0.009).
HBV pgRNA status at year 5 can reveal HBV covalently closed circular DNA (cccDNA) activity, and HBV pgRNA positivity after long-term antiviral therapy may indicate higher transcriptional activity of HBV cccDNA. Long-term dynamic monitoring of HBV pgRNA should be considered.

Copyright © 2021. Published by Elsevier Ltd.