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