HBcrAg correlated with intrahepatic HBV tDNA and cccDNA in 1 HBeAg-positive chronic hepatitis B patients 2

This study was to explore the correlation of serum hepatitis B core-related antigen 15 (HBcrAg) with intrahepatic HBV covalently closed circular DNA (cccDNA) and HBV 16 total DNA (tDNA) in HBeAg-positive chronic hepatitis B (CHB) patients. Serum 17 HBcrAg and other parameters including HBV DNA, HBV RNA, HBeAg, HBsAg, 18 anti-HBc, ALT, AST were quantitatively measured at baseline and follow-up time points. 19 Intrahepatic HBV cccDNA and tDNA were quantitatively detected at baseline and 20 96-week. Grading of liver necroinflammation and staging of hepatic fibrosis were 21 assessed at baseline and 96-week. Correlations between serum HBcrAg and other 22 parameters were analyzed by Pearson’s correlation analysis. The results showed that 23 pre-treatment HBcrAg correlated significantly with HBV tDNA level (r=0.328, P =0.003) 24 in 82 CHB patients, and intrahepatic HBV cccDNA (r=0.323, P =0.004) (n=79) after 25 removing three outliers. Serum HBcrAg correlated better with HBV cccDNA in patients 26 with lower level of serum HBV DNA (stratified by 7 log IU/ml of HBV DNA: r=0.656, 27 P =0.003 vs. r=-0.02, P =0.866). Significant inverse correlations were found between 28 HBcrAg and grade of liver necroinflammation (r=-0.245, P =0.037), stage of hepatic 29 fibrosis (r=-0.360, P =0.002) at baseline. Serum HBcrAg presented significant correlation 30 with intrahepatic HBV cccDNA in patients with HBeAg seroconversion at 96-week 31 (r=0.622, P =0.006). The decline in HBcrAg showed significant correlation with the 32 decline in HBV cccDNA after 96-week NAs therapy (r=0.282, also correlated significantly with other serum markers at baseline and 96-week of NAs therapy. In conclusion, baseline HBcrAg and its declined value were significantly 35 correlated with the corresponding intrahepatic HBV cccDNA. Intrahepatic cccDNA, and quantitatively tested at and follow-up time Correlations between serum HBcrAg and intrahepatic HBV cccDNA, HBV tDNA, HBV markers, stage of hepatic fibrosis, grade of liver necroinflammation and after 96 weeks NAs