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HBV RNA positivity at nucleoside analogue discontinuation linked to higher relapse risk in chronic hepatitis B

HBV RNA positivity at nucleoside analogue discontinuation linked to higher relapse risk in chronic h…
Photo by Dmytro Vynohradov / Unsplash
Key Takeaway
Consider HBV RNA status when evaluating relapse risk after nucleoside analogue discontinuation in chronic hepatitis B.

This systematic review and meta-analysis examined the relationship between HBV RNA status at nucleoside analogue discontinuation and subsequent relapse risk in chronic hepatitis B. The analysis pooled data from 21 observational cohort studies involving 2,043 individuals. The primary outcomes were viral relapse and clinical relapse following treatment cessation, though the specific follow-up duration was not reported for the overall analysis.

HBV RNA-positive individuals at discontinuation showed significantly higher relapse rates compared to HBV RNA-negative patients. Viral relapse was 1.9-fold higher (p < 0.0001), and clinical relapse was 2.26-fold higher (p < 0.0001). For each log10 copies/ml increase in HBV RNA levels at discontinuation, viral relapse risk increased 1.32-fold (p < 0.0001) and clinical relapse risk increased 1.37-fold (p < 0.0001). Clinical relapse was also associated with HBeAg positivity at baseline (p = 0.006). A subgroup analysis found no significant correlation between relapse rates and follow-up periods of 2 years or longer.

Safety and tolerability data were not reported in the meta-analysis. Key limitations include the observational nature of all included studies, which precludes establishing causality, and the absence of absolute event rates for relapse outcomes. Funding sources and conflicts of interest were not reported. The findings suggest HBV RNA surveillance may have prognostic value when considering nucleoside analogue discontinuation, particularly for HBeAg-positive patients, but clinical decisions should weigh these associations against the limitations of the evidence.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
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.
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