Stronger HBc-specific B cell activity in chronic HBV-infected children with higher liver inflammatory grade and better antiviral therapy response

Background Although the majority of children with chronic HBV infection (CHB) are asymptomatic and in the immune tolerance phase, some of them develop progressive liver disease. The mechanisms of the progression of liver disease in these CHB children remain largely unclear. Methods 20 CHB children were enrolled for comparison of hepatic transcriptome profiles between no-significant and significant liver inflammation, and analysis of the correlations between the hepatic gene expression and clinical parameters or anti-viral responses. Quantity, phenotype and function of peripheral B cell and HBc-specific B (HBc-B) cells were assessed in another 97 treatment-naïve CHB children during different clinical phases, in which 17 subsequently receiving ETV treatment for analysis of longitudinal changes in the peripheral HBc-B cells and their relationship to anti-viral responses. Results Bioinformatic analysis and liver biopsy staining revealed that remarkably enhanced hepatic B cell infiltration was the distinctive feature of CHB children with significant liver inflammation. Dramatically increased peripheral HBc-B cell frequency, HBcAb-secreting spot-forming cell (HBcAb SFC) count, and serum HBcAb level were observed in CHB children during immune active phase. HBcAb SFC count and HBcAb level were significantly positively correlated to liver inflammation grade or ALT level. Higher hepatic level of B cell-related genes, elevated percentage of peripheral HBc-B cell, and raised level of serum HBcAb were found in CHB children with more HBeAg decline at week 12 or 48 of ETV treatment. Conclusion Higher activity of HBc-B cells would be linked to increased liver inflammation and more favorable antiviral treatment outcomes in pediatric CHB patients.