External Validation of the GOLDEN Model for Predicting HBsAg Loss in Noncirrhotic Chronic Hepatitis B Patients With Interferon-Alpha-Based Therapy.

BACKGROUND & AIMS: GOLDEN model is designed to predict hepatitis B surface antigen (HBsAg) loss based on patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues therapy. We aimed to validate GOLDEN model's effectiveness in predicting HBsAg loss or decline in interferon-α-treated patients with CHB.

METHODS

Interferon-α-treated patients were enrolled from EXCEL study, a randomized controlled trial that included hepatitis B e antigen-positive, noncirrhotic, treatment-naive patients with CHB, and Search-B cohort, a prospective real-world observational cohort of CHB. Using multiple quantitative HBsAg (qHBsAg) measurements, GOLDEN model was used to calculate a patient's probability of achieving HBsAg loss or decline.

RESULTS

Among 200 patients in the EXCEL study and 1041 patients from the Search-B cohort, the corresponding cumulative incidence of qHBsAg <100 IU/mL or HBsAg loss was 20.0% and 6.7%, after the median follow-up of 18.0 (interquartile range, 18.0-30.0) and 66.7 (interquartile range, 48.8-84.7) months, respectively. The GOLDEN model achieved an area under the curve of 0.820 (95% confidence interval, 0.737-0.902) for predicting qHBsAg <100 IU/mL in the EXCEL study and 0.964 (95% confidence interval, 0.953-0.974) for predicting HBsAg loss in the Search-B cohort, maintaining robust performance across subgroups. The favorable group showed higher cumulative incidences of qHBsAg <100 IU/mL (42.5% vs 4.6%; P < .001) or HBsAg loss (37.2% vs 0%; P < .001) than the unfavorable group, along with significantly lower qHBsAg levels and faster qHBsAg decline rates. Moreover, the favorable group defined by GOLDEN model and qHBsAg levels at enrollment were confirmed as independent predictors for HBsAg loss or decline.

CONCLUSIONS

GOLDEN model is a robust tool for predicting HBsAg loss or decline in interferon-α-treated patients with CHB, offering valuable support for clinicians in developing personalized, effective management strategies for patients with CHB.