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

Gian Paolo Caviglia; Maria Lorena Abate; Daniele Noviello; Antonella Olivero; Chiara Rosso; Giulia Troshina; Alessia Ciancio; Mario Rizzetto; Giorgio Maria Saracco; Antonina Smedile

doi:10.1111/hepr.12811

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

Hepatol Res. 2017 Jul;47(8):747-754. doi: 10.1111/hepr.12811. Epub 2016 Sep 27.

Authors

Affiliations

¹ Department of Medical Sciences, University of Turin, Turin, Italy.
² Department of Gastroenterology, Città della Salute e della Scienza Hospital, Turin, Italy.
³ Department of Oncology, University of Turin, Turin, Italy.

PMID: 27577976
DOI: 10.1111/hepr.12811

Abstract

Aim: The 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)-α treatment in a cohort of chronic hepatitis B (CHB) genotype D patients.

Methods: One hundred thirty eight sequential serum samples were collected from 28 hepatitis B e antigen-negative CHB genotype D patients (20 men and 8 women; median age, 54 years [range, 47-58 years]) who underwent NA (n = 20) or PEG-IFN-α (n = 8) treatment. Serum HBcrAg levels were determined by chemiluminescent enzyme immunoassay. Longitudinal analysis was carried out at 6, 12, 24, and 36 months after NA treatment initiation and at 6, 12, and 18 months and at follow-up month 6 after PEG-IFN-α treatment.

Results: Basal HBcrAg levels were 4.7 ± 1.8 Log U/mL and 3.3 ± 1.6 Log U/mL in NA- and PEG-IFN-α-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 ± 0.6 Log U/mL), independently from HBV DNA and HBsAg kinetics.

Conclusions: Serum 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.

Keywords: hepatitis B core-related antigen; hepatitis B surface antigen; hepatitis B virus DNA; nucleos(t)ide analogue; pegylated-interferon-α.