1842 ♦
Predictive role of serum HBsAg and HBcrAg levels in
patients with HBeAg-negative chronic hepatitis B treated
with pegylated interferon-based therapy
Natthaya Chuaypen1, Nawarat Posuwan1, Sunchai Payungporn1,
Sombat Treeprasertsuk1, Yasuhito Tanaka2, Yong Poovorawan1,
Pisit Tangkijvanich1; 1Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand; 2Nagoya City University Graduate School
of Medical Sciences, Nagoya, Japan
Background: The role of serum hepatitis B core-related antigen
(HBcrAg) quantification in patients with chronic hepatitis
B (CHB) receiving pegylated interferon (PEG-IFN) remains
unclear. The aim of this study was to determine the predictive
role of serum HBsAg and HBcrAg levels in patients with
HBeAg-negative CHB during PEG-IFN-based therapy. Method:
A total of 121 Thai patients with HBeAg-negative CHB were retrospectively
analyzed. Among these, 62 and 59 patients were
treated with PEG-IFN monotherapy and PEG-IFN plus entecavir
for 48 weeks, respectively. Virological response (VR) was
defined as HBV DNA < 2,000 IU/mL at 48 weeks post treatment.
Paired liver biopsies at weeks 0 and 48 were assessed
for intrahepatic covalently closed circular DNA (cccDNA) by
real-time PCR. HBsAg and HBcrAg levels were analyzed by
automated chemiluminescent immunoassays. HBV genotype
was performed by direct sequencing. Results: The distribution
of genotypes B and C was 19% and 81%, respectively. The
overall VR was 48 (39.7%). There was no difference in VR
between monotherapy and combination therapy (41.9% vs
33.9%, P=0.710). Baseline HBcrAg, but not HBsAg was correlated
with cccDNA (Pearson correlation, r=0.380, P=0.001
and r=0.040, P=0.737, respectively). Changes in HBcrAg and
HBsAg levels during therapy were correlated with the reduction
of cccDNA (r=0.346, P=0.003 and r=0.335, P=0.004,
respectively). At baseline, responders had significantly lower
HBsAg levels than non-responders (3.3 ± 0.4 vs. 3.6 ± 0.5
log10IU/mL, P=0.006), but there were no difference between
groups in terms of HBcrAg (4.2 ± 1.3 vs. 4.3 ± 1.2 log10U/mL,
P=0.782) and cccDNA levels (0.5 ± 1.4 vs. 0.3 ± 1.0 log10
copies/cEq, P=0.591). In addition, responders showed more
rapid decline of both serum markers during and after therapy.
At weeks 4 and 12, the absence of HBsAg decline from baseline
yielded negative predictive values (NPV) of 72.7% and
81.0%, respectively. The corresponding figures for the absence
of HBcrAg decline were 68.4% and 73.5%, respectively.
When both criteria were used together, the NPV of achieving
VR at weeks 4 and 12 were 85.0% and 100%, respectively.
HBsAg decline from baseline ≥0.5 log10IU/mL at week 12
yielded a positive predictive value (PPV) of 77.5%, while the
corresponding figure for HBcrAg decline ≥0.5 log10U/mL was
52.3%. Patients in whom both declines were present had a
PPV of 84.2%. Conclusion: Quantitative HBcrAg represented
a surrogate marker of cccDNA in HBeAg-negative CHB. The
combined use of HBsAg and HBcrAg levels during PEG-IFNbased
therapy could identify patients with high or low probability
of response and may help individualize on-treatment
decision-making.
Disclosures:
Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD.,
MSD, abbvie, Bristol-Myers Squibb; Speaking and Teaching: Bristol-Myers
Squibb
The following people have nothing to disclose: Natthaya Chuaypen, Nawarat
Posuwan, Sunchai Payungporn, Sombat Treeprasertsuk, Yong Poovorawan, Pisit
Tangkijvanich