Low anti-HBc levels are associated with lower risk of virological relapse after nucleos(t)ide analogue cessation in HBe antigen-negative patients

Abstract

Background and Aims: Low anti-HBc serum levels at the time of therapy cessation were linked to a higher relapse risk in predominantly HBeAg-positive cohorts. We investigated the association of anti-HBc levels with relapse in HBeAg-negative patients. Methods: Serum levels of anti-HBc, HBsAg and HBcrAg were determined in 136 HBeAg-negative patients, participating in a vaccination trial (ABX-203, NCT02249988), before treatment cessation or vaccination. Importantly, vaccination showed no impact on relapse. The correlation between the biomarkers and their predictive value for relapse (HBV DNA >2000 IU/ml ± ALT >2xULN) was investigated. Results: After therapy cessation 50% (N = 68) of patients relapsed. Median anti-HBc prior to treatment stop was significantly higher among relapsers compared to off-treatment responders (520 IU/ml vs. 330 IU/mL, p =.0098). The optimal anti-HBc cut-off to predict relapse was 325 IU/ml according to the Youden-Index. About 35% of patients with anti-HBc level < 325 IU/ml versus 60% of those with values ≥325 IU/mL relapsed (p =.0103; sensitivity 50%, specificity 75%). Combining the optimal cut-offs of HBsAg (>3008 IU/mL) or HBcrAg (≥1790 U/ml) with anti-HBc increased the proportion of patients with relapse to 80% (p