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FUNCTIONAL CURE OF CHRONIC HEPATITIS B IS ASSOCIATED
WITH CO-OCCURRENCE OF HBsAg/ANTI-HBS IMMUNE
COMPLEXES WITH ALT FLARES, AND SEROCONVERSION TO
NEUTRALISING ANTI-HBS
Hui Xu1, Stephen Locarnini1, Darren Wong2, Renae Walsh1,
Sally Soppe1, Danni Colledge1, Rachel Hammond1, Alexander
Thompson3, Peter Revill4, Patrick Marcellin5, Anuj Gaggar6 and
Nadia Warner1, (1)Victorian Infectious Diseases Reference
Laboratories, (2)Gastroenterology, Gastroenterology, (3)
Medicine, University of Melbourne, (4)Victorian Infectious
Diseases Reference Laboratory, Royal Melbourne Hospital,
(5)Department of Hepatology, AP-HP Hôpital Beaujon, 92110
Clichy, France, (6)Gilead Sciences, Inc, Foster City, CA, USA
Background: HBsAg specific antibody responses during
chronic hepatitis B infection are poorly defined due to 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
patients undergoing nucleos(t)ide analogue (NA) treatment
were examined, 14 patients achieved functional cure while
11 patients remained infected HBsAg/anti-HBs Immune
complexes (HBs-IC) were quantified using an optimized
quantification 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 with a fluctuating profile of peaks and troughs.
In the 14 patients who achieved functional cure, 10 had an
ALT flare immediately prior to HBsAg loss and seroconversion
and of these 10 patients, nine had co-occurring HBs-IC
peaks Patients who did not clear the virus had lower anti-
HBs responses compared to those functional cured patients
Anti-HBs derived from functionally cured patients after
seroconversion was more potent in neutralizing HBV infection
in vitro, and recognised more anti-HBs epitopes compared
to anti-HBs from vaccinee controls Conclusion: Anti-HBs
responses are present and fluctuate during chronic hepatitis
B infection and are important for achieving functional cure
Functional cure in the analysed cohort was associated with
co-occurring HBs-IC peak and ALT flare prior to clearance,
and was followed by the production of anti-HBs that recognize
broad epitopes on HBsAg which potently neutralize HBV
infection Failure of virus clearance was associated with
inadequate anti-HBs responses in the early phase of NA
treatment These results further demonstrate the importance
of anti-HBs responses in clearing HBV infection.
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发表于 2020-10-31 19:47