E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Functional cure of chronic hepatitis B is associated with co-occurrence of HBsAg/anti-HBs immune complex peaks with ALT flares, and seroconversion to potently neutralising anti-HBs (#243)

Hui Xu 1 , Stephen Locarnini 1 , Darren Wong 2 , Rachel Hammond 1 , Sally Soppe 1 3 , Danni Colledge 1 , Tim Shaw 1 , Alexander Thompson 4 , Peter Revill 1 , Anuj Gaggar 5 , Renae Walsh 1 6 , Nadia Warner 1
  1. Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at Peter Doherty Institute, Melbourne, VIC, Australia
  2. Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  3. WHO collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute, Melbourne, VIC, Australia
  4. Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
  5. Gilead Sciences, Foster City, CA, USA
  6. ClearB Therapeutics, Boston, MA, USA

Background and Aims: HBsAg specific antibody responses during chronic hepatitis B infection are poorly defined due to the excessive amount of sub viral particles produced during infection and lack of standardised detection methodologies. The aim of this study was to investigate the nature of the anti-HBs responses in chronically infected HBV patients during the process of functional cure.

Methods: Longitudinal samples from 25 genotype A CHB patients undergoing nucleos(t)ide analogue (NA) treatment were examined, 14 of these patients achieved functional cure (FC) while 11 patients remained infected. HBsAg/anti-HBs Immune complexes (HBs-IC) were quantified using an in-house modification of a commercial diagnostic assay. Epitope-specific anti-HBs responses were detected using a 19-plex assay and neutralization efficacy of anti-HBs was measured using an in vitro HBV infection model.

Results: HBs-IC was detected in all patient’s serum samples at fluctuating levels. In the 14 patients who achieved functional cure, 10 had an ALT flare immediately prior to HBsAg loss, and of these 10 patients, 9 had co-occurring HBs-IC peak responses. This co-occurrence was not observed in non-functionally cured patients (non-FC). Non-FC patients had lower anti-HBs responses at week 12 of NA treatment compared to FC patients. Anti-HBs derived from FC patients after seroconversion was more potent in neutralizing HBV infection in vitro, and recognised more anti-HBs epitopes compared to anti-HBs from vaccinees.

Conclusions: Anti-HBs responses are present and fluctuate during chronic hepatitis B infection. Functional cure in the analysed cohort was associated with co-occurring HBs-IC peak and ALT flare prior to clearance, and was followed by seroconversion to anti-HBs with broad HBsAg epitope recognition, which potently neutralize HBV infection. Failure of virus clearance was associated with lower anti-HBs responses in the early phase of NA treatment. These results demonstrate the presence and importance of broadly-reactive anti-HBs responses in clearing HBV infection.