studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1205A
Anuj Gaggar - Employment: Gilead Sciences, Inc.
Mani Subramanian - Employment: Gilead Sciences
The following authors have nothing to disclose: Leszek Szenborn, Kyungpil Kim,
Luminita Luminos, Malgorzata Pawlowska, Jacek Mizerski
2044
The baseline combination of HBcrAg and HBsAg titers
enhance treatment outcome and HBsAg loss predictions
in HBeAg negative chronic hepatitis B patients treated
with pegylated interferon alfa-2a or PegIFN plus Tenofovir-disoproxil-fumarate.
Michelle Martinot-Peignoux 1,2 , Martine Lapalus 1 , Nathalie Boyer 2 ,
Corinne Castelnau 2 , Nathalie Giuily 2 , Michele Pouteau 2 , Rami
Moucari 1 , Tarik Asselah 2,1 , Patrick Marcellin 2,1 ; 1 Université Denis
Diderot Paris 7, INSERM, UMR1149, Centre de Recherche sur
l’Inflammation, Clichy, France; 2 Hôpital Beaujon AP-HP, Service
d’Hépatologie, Clichy, France
Background. It remains unclear whether adding a nucleot(s)ide
analogue (NAs) enhances the efficacy of pegylated interferon
alfa-2a (PegIFN) by accelerating HBsAg clearance. Baseline
HBsAg level is predictor of SVR in patients receiving PegIFN.
Hepatitis B core-related antigen (HBcrAg) is a new serological
HBV marker that could to be used for NAs treatment cessation.
It combines 3 viral proteins coded by the precore/core region
of the covalently closed circular DNA: HBeAg, HBcAg and
a core related protein (p22cr) by sharing a 149 amino-acid
sequence. We aimed to evaluate if the baseline combination
of HBcrAg and HBsAg levels might have a complimentary role
predicting treatment response, in patients receiving PegIFN)
therapy or PegIFN plus Tenofovir-disoproxil-fumarate (PegIF-
N+TDF) Patients-Methods. 62 patients HBeAg negative CHB
patients were treated with 48 weeks PegIFN or PegIFN+TDF.
Patients were followed 3 years after treatment cessation. HBsAg
and HBcrAg titers measured at baseline. HBsAg and HBV DNA
were measured at baseline, week 24, end of therapy (EOT),
24 weeks, 1, 2 and 3 years after treatment cessation. Results.
30 patients received PegIFN and 32 patients received PegIF-
N+TDF. The 2 groups of patients were similar with regards to
age, sex ratio, ALT levels, HBV genotypes distribution, histologic
lesions, mean HBsAg, HBcrAg and HBV DNA titers. An
EOT response was observed in 90% and 100% of PegIFN and
PegIFN+TDF patients, respectively. SVR was 10/30 (33%) and
17/32 (53%) in PegIFN and PegIFN+TDF patients, respectively.
At the end of 3 years post-treatment follow-up an HBsAg
loss was observed in 7/30 (1 at EOT) and 6/32 (4 at EOT) in
PegIFN and PegIFN+TDF patients, respectively. Baseline negative
predictive values (NPVs) for SVR of HBsAg threshold 3.302
log IU/ml and HBcrAg threshold 3.699 log U/ml and combination
of both thresholds were: 78% or 63%, 74% or 61%
and 80% or 75% in patients receiving PegIFN or PegIFN+TDF,
respectively. Baseline NPVs for HBsAg loss of HBsAg threshold
3.302 log IU/ml and HBcrAg threshold 3.699 log U/ml and
combination of both thresholds were: 88% or 100%, 79% or
89% and 87% or 100% in patients receiving PegIFN or PegIF-
N+TDF, respectively. Conclusions. In HBe negative patients,
our results indicate that the addition of TDF to PegIFN enhance
the rate of viral suppression with 53% SVR and 12.5% EOT
HBs loss, while SVR was observed in 33% and EOT HBs loss
in 3.3% patients receiving with PegIFN monotherapy. Baseline
combination of HBsAg and HBcrAg titers allows the identification,
prior therapy, of patients with low probability of SVR and
HBsAg loss indicating that these markers could be used for “à
la carte therapy”.
Disclosures:
Nathalie Boyer - Board Membership: MSD, JANSSEN, Gilead, Abbvie; Speaking
and Teaching: BMS
Tarik Asselah - Advisory Committees or Review Panels: AbbVie, Merck, Gilead,
BMS, Roche, Janssen
Patrick Marcellin - Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen,
MSD, Abbvie, Alios BioPharma, Idenix, Akron; Grant/Research Support: Roche,
Gilead, BMS, Novartis, Janssen, MSD, Alios BioPharma; Speaking and Teaching:
Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Boehringer, Pfizer,
Abbvie
The following authors have nothing to disclose: Michelle Martinot-Peignoux,
Martine Lapalus, Corinne Castelnau, Nathalie Giuily, Michele Pouteau, Rami
Moucari
2045
Baseline HBsAg titer allows identification of patients
that will benefit from pegylated interferon therapy and
experience an HBsAg loss.
Michelle Martinot-Peignoux 2,3 , Nathalie Boyer 3 , Corinne Castelnau
3 , Nathalie Giuily 3 , Michele Pouteau 3 , Martine Lapalus 1,2 , Rami
Moucari 1,2 , Tarik Asselah 3,1 , Patrick Marcellin 3,2 ; 1 Université Paris
Diderot, INSERM U773/CRB3 et Service d’hépatologie, Clichy,
France; 2 Université Denis Diderot Paris 7, INSERM, UMR1149,
Centre de Recherche sur l’Inflammation, Clichy, France; 3 Hôpital
Beaujon AP-HP, Service d’Hépatologie, Clichy, France
Background. A 48 weeks treatment with pegylated interferon
alfa-2a (PegIFN) is the only treatment allowing to obtain 30% of
sustained virological response (SVR) and 10% HBs loss within
3 years post-treatment follow-up. It is well demonstrated that
early on treatment HBs decline is predictive of response. We
aimed to evaluate the predictive value of baseline HBsAg titer
to predict SVR and HBs loss, in patients treated with PegIFN or
PegIFN plus Tenofovir-disoproxil-fumarate (PegIFN+TDF) Methods.
62 HBeAg(-) CHB patients treated for 48 weeks. HBsAg
and HBVDNA titers were measured at baseline, end of therapy
(EOT), 24 weeks, 1 2 and 3 years after treatment cessation.
HBV genotype distribution at baseline. Results. 30 patients
received PegIFN and 32 patients received PegIFN+TDF. An
EOT response was observed in 90% and 100% of PegIFN and
PegIFN+TDF patients, respectively. An SVR was observed in
27/ 62 (43%), 10/30 (33%) and 17/32 (53%) in the overall,
PegIFN and PegIFN+TDF patients, respectively. At the end of
3 years post-treatment follow-up an HBsAg loss was observed
in 13/62 (21%) 7/30 (23%) and 6/32 (19%), in the overall,
PegIFN and PegIFN+TDF patients, respectively. HBsAg and
HBV DNA titers were significantly higher in SVR than in non-responders
(p2000 IU/ml including
27/35 (77%) non-responders patients and 36/49 (74%)
patients with no-HBs loss within 3 years post-treatment follow-up.
The positive predictive value of HBsAg titer ≤ 2000UI/
ml for SVR and HBs loss were 67% and 46% or 55% and
45% or 77% and 46% in the overall population or patients
receiving PegIFN or PegIFN+TDF, respectively. The negative
predictive value (NPVs) of baseline HBsAg titer >2000 IU/ml
for SVR and HBs loss were 71% and 85% or 79% and 89% or
63% and 100% in the overall population or patients receiving
PegIFN or PegIFN+TDF, respectively. The NPVs for genotypes
A, B, D, and E, were 50%, 80%, 74% and 82%, respectively.
Conclusions. Our results show that at baseline an HBsAg threshold
of 2000 IU/ml is highly predictive of treatment response
and HBsAg loss in patients treated with 48 weeks of PegIFN
patients or PegIFN+TDF. Among the patients with an HBsAg
level ≤ 2000 IU/ml 59% demonstrated a SVR and 85% expe-