Factors Associated With Surface Antigen (HBsAg) Clearance in a Spanish Cohort of Chronic Hepatitis B Patients: Influence on the Long‐Term Prognosis

ABSTRACT The objective is to identify factors that contribute to hepatitis B surface antigen (HBsAg) clearance in patients with chronic hepatitis B (CHB) infection in an unselected, long‐term follow‐up hepatitis B open cohort in southern Spain. A prospective open cohort study of 453 patients with CHB infection was recruited in the Liver Unit of the Internal Department of two hospitals in Málaga (Spain) between 1991 and 2022 to assess the incidence of hepatitis B surface antigen (HBsAg) clearance during follow‐up, identify factors related to it, and determine the influence that clearance had on the long‐term prognosis. The duration of follow‐up ranged from 0.5 to 36.08 years. A multivariate Cox regression analysis was conducted to identify factors associated with HBsAg clearance. The impact of clearance on long‐term prognosis was evaluated using a combined prognostic end point: need for liver transplantation, liver complications, or liver‐related mortality. The construction of time‐to‐event curves was achieved by employing the Kaplan‐Meir method, with subsequent comparison of event occurrence between groups conducted via log‐rank test. During the subsequent follow‐up period, 96/453 patients (21.2%) lost surface antigen (1.96/100 patients per year). Multivariate Cox regression analysis identified as independent factors associated with HBsAg clearance: age at first assessment over 40 years: HR 2.21 (1.38–3.52); a baseline DNA HBV peak below 3.3log 10 (< 2000 IU/mL): HR 3.44 (2.01–5.89); loss of hepatitis B e‐antigen (HBeAg) during follow‐up: HR 7.23 (3.87–13.50). The incidence of HBsAg clearance was 1.96 cases/100 patient‐years. It was more frequent in patients older than 40 years, with baseline DNA‐HBV below 3.3 log 10 (< 2000 IU/mL), and in chronic HBeAg+ patients who lost HBeAg during follow‐up. HBsAg clearance was associated with a better long‐term hepatic prognosis.