Background
Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B (CHB). Serum levels of antibodies to HBcAg (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain.

Methods
Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in CHB patients who either initiated de novo PEG-IFN (n = 299; 195 HBeAg-positive), or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91, all HBeAg-positive). Associations were explored between anti-HBc and (1)serum biomarkers, (2)liver histology and (3)treatment response.

Results
We studied 390 patients. HBV-genotypes were A/B/C/D in 24/9/16/49%, and 72% were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc correlated with HBV DNA, HBcrAg, HBsAg and HBV RNA, but not with ALT. Higher anti-HBc was associated with more severe histological inflammatory activity (p < 0.001), irrespective of HBeAg-status. After de novo PEG-IFN, higher anti-HBc was associated with HBeAg-loss, sustained response, HBsAg-decline and HBsAg-clearance (p < 0.050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg-loss (p = 0.012).

Conclusions
Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favourable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory-therapy.

https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiac210/6590452