Combining HBV markers may better predict functional cure

Clinical takeaway: Quantitative HBsAg remains the most practical single marker for predicting functional cure in chronic hepatitis B, but combining it with other viral markers may improve treatment selection, response monitoring, and decisions about stopping nucleos(t)ide analogue therapy.

Suppressing hepatitis B virus (HBV) replication is achievable with current antiviral therapy, but functional cure—sustained loss of hepatitis B surface antigen (HBsAg)—remains uncommon. A new review suggests that combining established and emerging viral biomarkers could help clinicians better identify which patients are most likely to reach this goal.

Among individual markers, quantitative HBsAg (qHBsAg) currently has the strongest clinical utility. Lower baseline levels and early declines during pegylated interferon-alfa treatment consistently predict a greater likelihood of sustained HBsAg clearance, making qHBsAg a relatively practical and cost-effective option when broader testing is unavailable.

However, the review found that models combining multiple markers generally predicted functional cure more accurately than individual biomarkers in large chronic hepatitis B cohorts. Potential combinations include qHBsAg, HBV DNA, hepatitis B core-related antigen (HBcrAg), HBV RNA, and quantitative anti-HBc.

The authors propose using biomarker profiles at several points in care: before treatment to estimate the likelihood of functional cure, during therapy to assess response, when considering nucleos(t)ide analogue discontinuation, and after HBsAg loss to guide consolidation treatment. Viral markers should also be considered alongside factors such as age, sex, immune status, and previous treatment.

The approach is not yet a standardized clinical algorithm. Wider adoption will depend on standardized assays and prospective validation of multimarker models, but the review points toward a more individualized approach to HBV treatment rather than relying on a single laboratory measure.

“Functional cure remains the most realistic treatment goal for chronic hepatitis B because complete elimination of the virus is not yet possible,” said Qishui Ou, professor at Fujian Medical University. “Our review demonstrates that integrating multiple viral markers offers a more accurate and practical approach for predicting which patients are most likely to achieve sustained HBsAg loss, allowing clinicians to make more informed treatment decisions.”

Source: Ou Q, et al. (2026 Jul 27) Portal Hypertens Cirrhos. Advances in Viral Markers for Predicting Functional Cure of Chronic Hepatitis B