HBV RNA Predicts the Risk of Off-Treatment Relapse in Chronic Hepatitis B Patients With NAs Therapy: A Systematic Review and Meta-Analysis

Since there are currently few antiviral drugs that can effectively reduce hepatitis B surface antigen levels, the recurrence rate remains high in patients with chronic hepatitis B (CHB) after discontinuing nucleoside analogues (NAs) treatment. This study aims to provide recommendations for monitoring relapse after treatment cessation, while also elucidating the significance of HBV RNA in predicting relapse in CHB patients. Studies published between 2019 and 2025 were searched using PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, and Cqvip. There are 21 cohort studies included and 2043 individuals involved. In our study, HBV RNA-positive individuals had a 1.9-fold higher viral relapse (VR) rate and a 2.26-fold higher clinical relapse (CR) rate compared to negative patients (all p < 0.0001). Subgroup analyses indicated that HBeAg positive at baseline was associated with higher rates of CR (p = 0.006) and no significant correlation between longer follow-up period following the cessation of NAs therapy (≥ 2 years) and higher VR or CR. For each log10 copies/ml increase in HBV RNA levels at discontinuation, there was a 1.32-fold increase in VR and a 1.37-fold increase in CR (all p < 0.0001). Our findings evaluated the relationship between HBV RNA status and levels at the time of NAs discontinuation and post-discontinuation relapse, highlighting HBV RNA as a helpful post-treatment biomarker for predicting relapse. HBV RNA surveillance is essential for patients discontinuing therapy following NAs, particularly for those who are HBeAg-positive at baseline.