Author information
1 Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Victoria, Australia.
2 Abbott Laboratories, Chicago, Illinois, USA.
3 Gilead Sciences, Foster City, California, USA.
4 Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia.
Abstract
BACKGROUND AND AIM:
Functional cure is the major goal of CHB therapy though few biomarkers predict this outcome. HBsAg epitope occupancy can be influenced by therapeutic and immune pressure. The aim of this study was to map the HBsAg epitope profiles during long term nucleos(t)ide analogue therapy in patients with genotype A CHB, in the context of HBsAg loss/seroconversion.
METHODS:
We evaluated 25 genotype A CHB patients in the GS-US-174-0103 trial of HBeAg-positive CHB patients treated with tenofovir or adefovir for 4 years, 14 who achieved HBsAg loss whilst 11 had no change. We epitope mapped the major domains of HBsAg to identify those patients with HBsAg clearance profile (loss of binding at both loops 1 and 2 epitopes of the "a" determinant) versus non-clearance profile (no change in epitope recognition, or loss of epitope binding at one loop only), correlating this to on-treatment HBsAg responses. Complexed anti-HBs was also measured.
RESULTS:
Analysis of the HBsAg epitope profiles of the 25 patients at baseline identified no predictive correlation with HBsAg loss. In contrast, analysis at week 48 and end of study (week 192) or prior to HBsAg loss identified significant predictive associations between development of HBsAg clearance profiles and outcome of functional cure. The detection of a clearance profile also correlated with the development of an ALT flare and detection of anti-HBs complexed with HBsAg.
CONCLUSION:
The detection of HBsAg clearance profiles by epitope mapping represents a novel viral biomarker, reflecting an emerging anti-HBs selection pressure prior to functional cure.