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 < .0001) and 74% ( p = .0006), respectively. Conclusion In contrast to predominantly HBeAg‐positive cohorts, in our cohort of HBeAg‐negative patients lower anti‐HBc levels are associated with a significantly lower relapse risk after nucleos(t)ide analogue cessation. The vast majority of included patients were either genotype B or C and the applicability to other genotypes has to be further evaluated. However, anti‐HBc level as an indicator of the host response might be prospectively further explored for prediction models.