Abstract: Objective To investigate serum HBV RNA levels in HBeAg-positive chronic hepatitis B patients with low-level viremia(LLV)following long-term nucleoside/nucleotide analogues(NAs)therapy and to assess changes after NAs intervention. Methods This was a nested case-control study and patients with LLV were matched 1∶1 with who achieved a maintained virological response(MVR)after antiviral therapy. LLV patients were then categorized into an NAs intervention group and a control group based on their willingness to undergo further treatment. Clinical data were collected and followed up. Serum HBV RNA was quantified using the Specific RNA Target Capture combined with the Simultaneous Amplification and Testing(SAT)method. Results A total of 62 LLV patients and 62 MVR patients were enrolled. Serum HBV RNA levels are higher in the LLV group compared with the MVR group at baseline, 24 weeks and 48 weeks of follow-up(P<0.001). During the follow-up period, serum HBV RNA decreased from baseline in the LLV patients, but the results were not statistically different. The decrease in serum HBV RNA changes in LLV patients in the control and intervention groups followed up to 24 and 48 weeks only decreased in the intervention group at 48 weeks, but there was no statistically significant difference. Conclusion Serum HBV RNA levels are higher in the LLV patients compared to the MVR group and decline slowly. The decrease in HBV RNA levels after adjustment for NAs treatment is not significant compared to the maintained regimen group. It is suggested that combinations of other interventions are necessary to further reduce HBV transcriptional activity.

Key words: Low-level viremia, Maintained virological response, Hepatitis B virus RNA, Nucleoside/ nucleotide analogues, Hepatitis B e antigen