The HBsAg/HBV DNA ratio’s potential for predicting disease progression

Patients with chronic hepatitis B virus (HBV) infection in the immune-tolerant phase may still experience hepatic inflammation and disease progression, and could benefit from early antiviral treatment.

This study aimed to investigate changes in the cumulative hepatitis B surface antigen (HBsAg)/HBV DNA ratio in immune-tolerant patients during the transition to the immune-active phase, and to evaluate its potential in predicting the risk of disease progression.

Methods

This longitudinal study included 127 untreated immune-tolerant patients, who were followed for up to 10 years. An independent cohort of 109 subjects was retrospectively enrolled for external validation. The relationship between the cumulative HBsAg/HBV DNA ratio and the duration of immune tolerance or transition to the immune-active phase was examined. The predictive value of the ratio was assessed and validated.

Results

The relationship between the cumulative HBsAg/HBV DNA ratio and disease progression risk showed a non-linear pattern: below a ratio of 1.791, the risk of disease progression decreased rapidly as the ratio increased; above 1.791, the risk plateaued. The area under the curve for predicting disease progression was 0.67, 0.64, and 0.85 for cumulative HBsAg, HBV DNA, and the HBsAg/HBV DNA ratio, respectively.

Multivariable Cox regression analysis revealed the cumulative HBsAg/HBV DNA ratio as an independent predictor of disease progression, with higher ratios associated with a lower risk. Prediction models incorporating this ratio were developed and externally validated, demonstrating strong performance and clinical utility.

Conclusions

This study identifies the cumulative HBsAg/HBV DNA ratio as an independent predictor of immune tolerance duration in patients with chronic HBV infection. A lower ratio correlates with an increased risk of transition from the immune-tolerant phase to the immune-active phase, particularly when it falls below 1.791, at which point the risk of disease progression increases sharply.

Additionally, patients aged ≥30 years face a notably higher risk of disease progression, underscoring the need for vigilant monitoring in this population. These findings have important implications for the proactive management of immune-tolerant patients. Early detection of disease progression and timely antiviral treatment may ultimately improve clinical outcomes and societal benefits for individuals suffering from chronic HBV infection.