Incidence and prediction of HBsAg seroclearance in a prospective multi‐ethnic HBeAg‐negative chronic hepatitis B cohort

Background and Aims Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics. Methods The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg‐negative patients (1150 adults, 90 children) with median follow‐up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti‐HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated. Results Crude incidence rates of HBsAg loss and anti‐HBs acquisition were 1.6 and 1.1 per 100 person‐years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non‐Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV‐DNA levels, and lower and greater change in qHBsAg. The HBRN‐SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987–1.00) and 0.95 (95% CI 0.91–1.00), respectively. In validation in another cohort of 1253 HBeAg‐negative patients with median follow‐up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98–1.00) and 0.88 (0.77–0.99), respectively. Conclusion HBsAg loss in predominantly untreated patients with HBeAg‐negative CHB can be accurately predicted over a 3‐year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.