Intrahepatic and peripheral immunophenotyping of participants with chronic hepatitis B receiving bepirovirsen in the B-Fine study strongly suggests that bepirovirsen may trigger a humoral response

Background Evidence suggests a role for B-cells in immune responses to hepatitis B virus (HBV) infection and bepirovirsen, an unconjugated antisense oligonucleotide in development for chronic HBV infection. This open-label Phase 2a study (NCT04544956) investigated how bepirovirsen impacts B-cell and humoral responses by analyzing matched liver fine needle aspirates (FNA) and peripheral blood from bepirovirsen-treated participants with chronic HBV infection. Methods Participants on stable nucleos(t)ide analogs, with HBsAg>100 IU/mL, received bepirovirsen 300 mg for 12 weeks. Biomarker analyses included RNA sequencing (RNA-seq) of whole blood and single cells (sc) recovered from the liver by FNA, serum proteomics and flow cytometry on peripheral blood mononuclear cells (PBMCs). Differential expression analysis was used to identify peripheral transcriptomic/proteomic changes in gene/protein expression and investigate immune mechanisms of HBsAg decline in the liver. Primary endpoint was HBsAg loss (