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

Abstract

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.

Review article: hepatitis B core‐related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection

“…For PEG‐IFN treatment, 2 studies exploring the decline of cccDNA and HBcrAg found conflicting results. While one study described a similar and significant decline of HBcrAg levels as cccDNA, the other study did not find a significant decline of HBcrAg with PEG‐IFN (Table ) . The number of patients in these 2 studies were too small (N = 58 and 8 respectively) to demonstrate any specific pattern of HBcrAg levels during PEG‐IFN therapy.…”

Hepatitis B virus core‐related antigen as a surrogate marker for covalently closed circular DNA

“…Several reports have demonstrated that serum HBcrAg levels correlate with disease phases and reflect serum HBV DNA levels . In addition, baseline HBcrAg level has been shown to be associated with lamivudine resistance, viral relapse after lamivudine withdrawn, and response to pegylated‐interferon therapy . Previously, we have performed a study with 54 patients using a manual prototype of the HBcrAg assay and found that HBcrAg correlates well with cccDNA .…”

“…[16][17][18][19] In addition, baseline HBcrAg level has been shown to be associated with lamivudine resistance, viral relapse after lamivudine withdrawn, and response to pegylated-interferon therapy. [20][21][22][23][24][25] Previously, we have performed a study with 54 patients using a manual prototype of the HBcrAg assay and found that HBcrAg correlates well with cccDNA. 18 A more recent study with 57 patients has also demonstrated a good correlation between HBcrAg and cccDNA in the HBeAg-negative patients.…”

Proposed model for the prediction of intrahepatic covalently closed circular DNA level in patients with chronic hepatitis B

“…Current nucleoside analogue (NA) therapies are able to efficiently suppress hepatitis B virus (HBV) replication. Current official guidelines recommend either entecavir or tenofovir disoproxil fumarate as first‐line NAs in CHB subjects owing to their potent HBV suppression with a minimal risk of drug resistance and a beneficial effect for the prevention of HCC development . However, these NAs cannot eliminate intrahepatic HBV covalently closed circular DNA (IH‐cccDNA) which persists in hepatocyte nuclei, resulting in difficulties for completely removing viruses .…”

“…Current official guidelines recommend either entecavir or tenofovir disoproxil fumarate as first-line NAs in CHB subjects owing to their potent HBV suppression with a minimal risk of drug resistance and a beneficial effect for the prevention of HCC development. [9][10][11][12][13][14] However, these NAs cannot eliminate intrahepatic HBV covalently closed circular DNA (IH-cccDNA) which persists in hepatocyte nuclei, resulting in difficulties for completely removing viruses. 15 As NAs are inhibitors for reverse transcriptase, they do not have direct efficacy on lowering IH-cccDNA levels.…”