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729
HBsAg/ANTI-HBS IMMUNE COMPLEXES PERSIST AFTER
HBsAg CLEARANCE
Pir Ahmad Shah1, Satinder Pal Kaur2, Mark Anderson3,
Vera Holzmayer3, Jeffrey Gersch3, Gavin Cloherty3, Mary
Kuhns3 and Daryl Lau1, (1)Medicine, Beth Israel Deaconess
Medical Center, Harvard Medical School, (2)Division of
Gastroenterology and Hepatology, Beth Israel Deaconess
Medical Center, Harvard Medical School, (3)Abbott
Diagnostics, Abbott Park, IL, USA
Background: Functional cure with HBsAg clearance is a
desirable treatment endpoint HBsAg and anti-HBs can form
immune complexes (IC) during the course of HBV infection
With HBsAg seroconversion, there are detectable unbound
anti-HBs antibodies in addition to HBsAg loss We applied
an investigational IC assay to evaluate the dynamics of the
virological parameters leading to functional cure Patients
and Methods: 21 CHB patients with either spontaneous
(n=10) or nucleos(t)ide analog (NA)-induced (n=11) HBsAg
loss were included The Abbott ARCHITECT HBsAg NEXT
Qualitative (sensitivity 0 005 IU/ml), Architect quantitative
HBsAg (qHBsAg), anti-HBs, and IC assays were performed
on serial serum samples IC assay uses anti-HBs monoclonal
antibodies to capture the HBsAg complexed with patient-derived
anti-HBs (huIgG) After eliminating the unbound
huIgG, an acridinylated secondary mouse anti-huIgG
antibody binds to the huIgG on the IC A chemiluminescent
reaction is induced with the acridinium and the resulting light
signal is reported in Relative Light Units (RLUs) Results:
There were 16 (76%) males and 10 (48%) Asians in this
cohort They all had undetectable HBsAg by the ARCHITECT
HBsAg NEXT Qualitative assay 11 patients in the treatment
group had HBeAg (-) CHB and received NA between 0 5
and 16 years prior to HBsAg loss The 10 with spontaneous
HBsAg loss were monitored for 3 to 7 years prior to HBsAg
clearance Patients were subsequently monitored for up to
6 years 9 (43%) patients achieved HBsAg seroconversion
with persistently detectable anti-HBs; 6 of 9 were in the
treatment group Patients with anti-HBs (+) had a more rapid
reduction in quantitative HBsAg (qHBsAg) prior to HBsAg
loss compared to those without [2 2 vs 0 8 log IU/ml/year
(p=0 04)] Interestingly, regardless of the anti-HBs status, IC
was detectable in all the patients prior to and after HBsAg loss
The IC values were higher among the anti-HBs (+) patients at
the time of HBsAg clearance; this difference, however, was
not statistically significant. (Figure) IC remained detectable
for those with over 5-year follow-up after HBsAg clearance
Conclusion: In this cohort of patients with either spontaneous
or treatment-induced functional cure, HBsAg reduction was
faster among those who developed anti-HBs This likely
attributes to the role of humoral immunity in viral clearance
The persistence of HBsAg/ anti-HBs immune complexes after
HBsAg seroconversion suggests that HBsAg continues to be
present even with detectable unbound anti-HBs antibodies
The quantitation of IC may provide insight on the risk of
hepatitis B reactivation after HBsAg loss Longer term followup
will be necessary to determine the dynamics of the free
anti-HBs and the HBsAg/ anti-HBs immune complexes over
time.
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