External validation of the GOLDEN model for predicting HBsAg loss in non-cirrhotic chronic hepatitis B patients with interferon-alpha based therapy.

Abstract

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

Methods: IFN-α-treated patients were enrolled from EXCEL study, a randomized controlled trial included HBeAg-positive, non-cirrhotic, treatment-naïve CHB patients, as well as Search-B cohort, a prospective real-world observational cohort of CHB. Utilizing multiple quantitative HBsAg (qHBsAg) measurements, GOLDEN model was employed to calculate patient's probability of achieving HBsAg loss or decline.

Results: Among 200 patients in EXCEL study and 1041 patients from 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 (IQR,18.0-30.0) and 66.7 (IQR,48.8-84.7) months, respectively. The GOLDEN model achieved an area under the curve of 0.820 (95% CI:0.737-0.902) for predicting qHBsAg<100 IU/mL in EXCEL study and 0.964 (95% CI:0.953-0.974) for predicting HBsAg loss in 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<0.001) or HBsAg loss (37.2% vs. 0%, p<0.001) 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 enrolment were confirmed as independent predictors for HBsAg loss or decline.

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