Hepatitis B core-related antigen kinetics in chronic hepatitis B virus genotype D-infected patients treated with nucleos(t)ide analogues or pegylated-interferon-

AimThe aim of this study was to evaluate the correlation between hepatitis B core-related antigen (HBcrAg) and hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels, and to investigate HBcrAg kinetics during nucleos(t)ide analogue (NA) or pegylated-interferon (PEG-IFN)- treatment in a cohort of chronic hepatitis B (CHB) genotype D patients. MethodsOne hundred thirty eight sequential serum samples were collected from 28 hepatitis B e antigen-negative CHB genotype D patients (20men and 8 women; median age, 54years [range, 47-58years]) who underwent NA (n=20) or PEG-IFN- (n=8) treatment. Serum HBcrAg levels were determined by chemiluminescent enzyme immunoassay. Longitudinal analysis was carried out at 6, 12, 24, and 36months after NA treatment initiation and at 6, 12, and 18months and at follow-up month 6 after PEG-IFN- treatment. ResultsBasal HBcrAg levels were 4.71.8Log U/mL and 3.3 +/- 1.6Log U/mL in NA- and PEG-IFN--treated patients, respectively. Hepatitis B core-related antigen showed a moderate correlation with HBV DNA (r=0.498, P<0.0001) and no correlation with HBsAg (r=0.192, P=0.0669). In serial serum samples, a significant HBcrAg reduction was observed only in patients receiving NA (P=0.019). In these patients, we observed a group (n=12) with an early HBcrAg decline to undetectable levels between months 6-12, whereas the other group (n=8) still had detectable HBcrAg at month 36 (4.4 +/- 0.6Log U/mL), independently from HBV DNA and HBsAg kinetics. ConclusionsSerum HBcrAg correlates with HBV DNA levels, most likely through expression of viral replication activity. We observed two different HBcrAg kinetics in NA-treated patients, suggesting different relapse risk related to NA cessation. Further studies on larger patient cohorts will elucidate the role of HBcrAg in the safe discontinuation of NA in CHB genotype D patients.