Characteristics of HBV Novel Serum Markers across Distinct Phases in Treatment-Naïve Chronic HBV-Infected Patients

METHODS: A total of 111 patients in total from different disease phases were recruited, including 21 in immune-tolerant (IT) phase, 49 in immune-clearance (IC) phases, 29 in immune-control or low replicative (LR) phase, and 12 in reactivation phases. Serum HBV RNA, anti-HBc, HBcrAg, and intrahepatic covalently closed circular DNA (cccDNA) were quantified and each of these indicator's correlation with liver inflammation was analyzed. RESULTS: HBeAg-positive individuals had significant higher serum levels of HBV RNA and HBcrAg than those who were HBeAg negative, similar to that of serum HBV DNA. Comparatively, HBV RNA (r =0.79, P < 0.01) and HBcrAg (r =0.78, P < 0.01) had almost same higher overall correlation with the cccDNA, as that of HBV DNA (r =0.81, P < 0.01). Serum anti-HBc level (r = -0.52, P < 0.05) is negatively correlated with cccDNA level at IT phase rather than the other three phases. When set the cutoff value at 4.00 log(10) IU/mL, serum anti-HBc showed potential to indicate liver inflammation, with AUC as 0.79 and the specificities as 78.85% for HBeAg positive, and with AUC as 0.72 and the specificities as 62.16% for HBeAg-negative patients, respectively. CONCLUSIONS: In treatment-naïve patients, levels of serological markers HBV RNA and HBcrAg could mirror intrahepatic cccDNA level, but were not superior to HBV DNA level. Serum anti-HBc level had certain potential to be used as a predicting marker for liver inflammation.