studies

964A AASLD ABSTRACTS HEPATOLOGY, October, 2015
Wai-Kay Seto - Advisory Committees or Review Panels: Gilead Science; Speaking
and Teaching: Bristol-Myers Squibb
Man-Fung Yuen - Advisory Committees or Review Panels: GlaxoSmithKline,
Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer,
GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Bristol-Myers
Squibb, Pfizer; Grant/Research Support: Roche, Bristol-Myers Squibb,
GlaxoSmithKline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmith-
Kline, Gilead Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead
Science, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Science
The following authors have nothing to disclose: James Fung, Danny Wong
1546
Assessing the impact of hepatitis B immune globulin
(HBIG) on responses to the hepatitis B vaccine during
co-administration
Qingwen Cui 1 , Iryna Zubkova 1 , Trudy Murphy 2 , Sarah F. Schillie 2 ,
Marian E. Major 1 ; 1 CBER/FDA, Alexandria, VA; 2 Division of Viral
Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA
Background: Administration of hepatitis B vaccine (HepB) and
hepatitis B immune globulin (HBIG) is recommended for infants
born to hepatitis B virus (HBV) carrier mothers and for exposed
persons with no known HBV protection. The recommended prophylaxis
for infants typically consists of HepB and HBIG at birth
followed by vaccination at 1 and 6 months; recommendations
specify administering HepB and HBIG via the intramuscular
(i/m) route at different sites. However, there are documented
instances of HepB and HBIG being administered at the same
site (i.e., in the same limb) and the impact of this on immune
responses to the vaccine remains unanswered. Our goal was
to address this issue through a series of studies immunizing
mice with a licensed HepB (GSK Engerix-B) alone or in combination
with HBIG (Nabi-HB, Biotest Pharmaceuticals). BALB/c
mice have been routinely used for in vivo potency assays for
HepB and provide a viable model to study responses. Methods:
Six week old mice (15/group) were immunized i/m with
HepB and/or HBIG at a 1:1 v/v ratio at 0, 4, and 16 weeks.
Groups consisted of: 1) HepB alone 2) HepB in one leg, HBIG
in a different leg (HepB boost at 4 and 16 wks) 3) HepB and
HBIG at the same site in the same leg (HepB boost at 4 and 16
wks) 4) HepB and HBIG mixed prior to administration (O/N
+4C) (HepB boost at 4 and 16 wks) 5) HBIG alone (no HepB
boost) 6) Untreated. Animals were bled at 2, 6 and 26 weeks
and sera were assessed for anti-HBs titers using a commercial
assay. Results: At week 26 we observed 100% seroconversion
(>10mIU/mL) in all groups that received HepB, regardless
of how HepB was administered with HBIG. However, we
observed significantly lower anti-HBs titers at 26 weeks when
HBIG and HepB were administered in the same limb (Gp3)
or after incubation overnight (Gp4) compared to HepB alone
(Gp1) (p=0.01 and p=0.02, respectively). At week 2 post
inoculation, prior to the development of responses to vaccine,
circulating levels of HBIG were lower in Gp3 mice (p=0.07;
87% seropositive) and Gp4 mice (p=0.001; 66% seropositive)
that received HepB and HBIG in the same limb compared to
those that received HBIG and HepB in different limbs (Gp2).
We observed similar results following inoculation of 3 week
old mice to simulate neonates. Conclusions: Administration of
HepB and HBIG in the same limb does not impact the long-term
response to HepB in either adult or young mice. However,
this incorrect method of administration can impact the initial
levels of circulating HBIG prior to the development of adaptive
immune responses which in some individuals could result in no
protective antibody levels during the first weeks after exposure
to HBV.
Disclosures:
The following authors have nothing to disclose: Qingwen Cui, Iryna Zubkova,
Trudy Murphy, Sarah F. Schillie, Marian E. Major
1547
End-of-therapy Serum Gradient of Hepatitis B Surface
Antigen Predicts Off-therapy Durability after Discontinuation
of Nucleos(t)ide Analogues
Yao-Chun Hsu 1,2 , Chun-Ying Wu 3 , Chi-Yang Chang 1 , Ming-Shiang
Wu 7 , Jia-Horng Kao 4 , Tzeng-Huey Yang 5 , Hsu-Wei Hung 8 ,
Jaw-Town Lin 6 ; 1 Division of Gastroenterology, E-Da Hospital, Kaohsiung,
Taiwan; 2 School of Medicine, I-Shou University, Kaohsiung
City, Taiwan; 3 Division of Gastroenterology, Taichung Veterans
General Hospital, Taichung City, Taiwan; 4 Graduate Institute of
Clinical Medicine, National Taiwan University, Taipei City, Taiwan;
5 Division of Gastroenterology, Lotung Poh-Ai Hospital, Yilan
County, Taiwan; 6 School of Medicine, Fu Jen Catholic University,
New Taipei City, Taiwan; 7 Department of Internal Medicine,
National Taiwan University, Taipei City, Taiwan; 8 Taipei Institute
of Pathology, Taipei City, Taiwan
Background and Aims: Relapse of chronic hepatitis B (CHB)
is common but remains unpredictable after discontinuation of
nucleos(t)ide analogues (NAs). This multicenter prospective
research aimed to explore the association between serum gradient
of hepatitis B surface antigen (HBsAg) and off-therapy
durability following NA cessation. Methods: From July 2011
through December 2014, 228 consecutive CHB patients who
were about to discontinue NAs were screened from 3 teaching
hospitals in Taiwan. Those who had achieved undetectable
viral DNA after a minimum of 3-year therapy were included.
Participants were monitored until February 2015 for occurrence
of clinical relapse, stringently defined as viral DNA >2,000IU/
mL plus ALT >2 folds upper normal limit for ^3 months, and
viral relapse, simply defined as viral DNA>2,000 IU/mL. Incidences
of relapse were evaluated by the Kaplan Meier method
and risk predictors determined by the Cox proportional hazard
analysis. Results: Among 158 eligible patients observed for a
mean duration of 14.6 (range, 3-42.2) months, clinical and
viral relapses occurred in 44 and 103 patients, respectively,
corresponding to 2-year cumulative incidences of 46.2% (95%
CI, 35.2-58.8%) and 81.6% (95% CI, 72.9-88.8%), respectively.
In 119 patients with negative HBeAg at NA cessation,
end-of-therapy HBsAg was associated with both clinical and
viral relapse in a dose-response manner (Ptrend=0.02 for clinical
and 0.0005 for virological relapse). Patients whose serum
HBsAg fell below 100 IU/mL did not develop clinical relapse
but could experience viral relapse with a cumulative incidence
of 33.4% (95% CI, 14.6-64.7%) at 2 years. In those with
HBsAg