Predictors of sustained functional cure in hepatitis B envelope antigen‐negative patients achieving hepatitis B surface antigen seroclearance with interferon‐alpha–based therapy

Abstract Hepatitis B surface antigen ( HB sAg) loss is considered a functional cure in chronic hepatitis B ( CHB ). However, the durability of HB sAg loss after stopping treatment remains unknown. This study aimed to assess the sustained functional cure achieved by interferon therapy in hepatitis B envelope antigen ( HB eAg)‐negative CHB patients. In this prospective study, 176 HB eAg‐negative CHB patients with functional cure were enrolled for 12 weeks of cessation treatment, and treatment information and baseline data were collected. Hepatitis B virus ( HBV ) biomarkers and clinical biochemical indicators were evaluated every 3 months; liver imaging examinations were performed every 3‐6 months during the 48‐week follow‐up. The sustained functional cure was evaluated. After the 48‐week follow‐up, the sustained functional cure rate was 86.63%. The cumulative rates of HB sAg reversion and HBV DNA reversion were 12.79% and 2.33%, respectively. Consolidation treatment ≥ 12 weeks after HB sAg loss achieved a significantly higher rate of sustained functional cure and significantly lower rate of HB sAg reversion than consolidation treatment < 12 weeks (76.19% vs 90.00%, P = 0.022 and 23.81% vs 9.23%, P = 0.014, respectively). Patients with hepatitis B surface antibody ( HB sAb) had higher rate of sustained functional cure than patients achieving HB sAg loss but without HB sAb (89.86% vs 73.53%, P = 0.012). Consolidation treatment ≥ 12 weeks (odds ratio [ OR ] 16.478; 95% confidence interval [ CI ], 2.135‐127.151; P = 0.007) and high HB sAb levels ( OR 8.312; 95% CI , 1.824‐37.881; P = 0.006) were independent predictors of sustained functional cure. Results suggested that 12 weeks of consolidation therapy after HB sAg clearance and elevated HB sAb levels help to improve functional cure.