HBV Antigen‐Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure

Little is known for factors associated with virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) to pegylated interferon alpha (Peg‐IFN‐α) for patients with chronic hepatitis B (CHB). Eighty patients who received 48‐week Peg‐IFN‐ɑ and NA combination therapy followed by Peg‐IFN‐ɑ monotherapy for additional 48 weeks were included in this study. HBV‐related markers including HBV DNA, HBsAg, HBcrAg, HBeAg, cccDNA, and immunological biomarkers were dynamically evaluated. Twelve (15.0%) patients experienced VBT after switching to Peg‐IFN‐ɑ and exhibited significantly lower rates of HBsAg loss after therapy completion (0% vs. 35.3%, p = 0.014). The patients with HBcrAg≥ 5 log10U/mL and HBsAg≥ 100 IU/mL had the highest risk of VBT and failed to achieve subsequent HBsAg clearance. Intrahepatic cccDNA level was significantly higher in patients with HBcrAg≥ 5 log10U/mL than those with HBcrAg