Background Relapse must be expected in > 50% of HBeAg negative patients after nucleos(t)idanalogue
(NA) cessation. Reliable biomarker for a safe therapy discontinution, next to HBs-Ag
are missing. Recently, a low anti-HBc-level was linked to a higher relapse-risk in
a cohort of predominantly HBeAg positive patients. This study investigated the association
of serum anti-HBc-level with relapse after NA cessation in HBeAg negative patients.
Methods Before NA cessation level of anti-HBc, HBsAg and HBcrAg were determined in 136 HBeAg
negative patients, participating in a therapeutic vaccination trial (ABX-203,NCT02249988).
Importantly, the partly performed concomitant therapeutic vaccination showed no impact
on relapse. Relapse was defined as HBV DNA > 2,000 IU/ml. Anti-HBc-level were compared
between relapsers and off-treatment responders using the Mann-Whitney U test. Optimal
anti-HBc threshold and correlation between the biomarker was determined by the Youden-index
and Spearman-correlation, respectively.
Results No correlation was found between baseline anti-HBc and HBsAg (r=0.016,p=0.85) or
anti-Hbc and HBcrAg (r=-0.011;p=0.90). Relapse occurred in 68 patients (50%). Median
anti-HBc-level was significant higher compared to off-treatment responders (520 IU/ml
vs. 330 IU/ml,p=0.0098). The optimal anti-HBc cut-off to predict relapse was determined
as 325 IU/ml. 35% of patients with an anti-HBc-level < 325 IU/ml relapsed, while this
was the case in 60% of those with values ≥ 325 IU/ml (p=0.0103; sensitivity 50%,specificity
75%).
Conclusion In contrast to a cohort of predominantly HBeAg positive patients, lower anti-HBc-level
are associated with a significant lower relapse-risk after NA cessation in HBeAg negative
patients. Anti-HBc-level should be further explored for the etablishment of prediction
models in the future.
