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

Abstract

HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

“…Thus, monitoring intrahepatic cccDNA levels could reflect the real activity of HBV replication in patients, and low levels of intrahepatic cccDNA could also predict sustained virologic response after cessation of antiviral therapy . In recent years, several HBV‐associated serum markers (including serum HBcrAg, HBsAg and HBV RNA) were all reported to be a potential indicator of intrahepatic cccDNA activity in different studies, and low level of serum HBcrAg or loss of serum HBV RNA also might indicate exhausting or transcription silencing of cccDNA reservoirs . To our knowledge, the present study represents a truly “real‐life” correlation analysis of serum HBcrAg and HBV RNA levels, and a first head‐to‐head comparison of serum HBcrAg, HBsAg and HBV RNA levels in reflecting intrahepatic cccDNA levels.…”

“…Currently, the most attractive viral proteins should be serum HBcrAg and HBsAg, and both of them can be found in mature virions as well as HBV DNA‐negative empty particles. The effectiveness of either serum HBcrAg or HBsAg in reflecting intrahepatic cccDNA level had been identified in cohorts of patients with different races and viral genotypes . Though a positive correlation was reported between HBcrAg and HBsAg in HBeAg‐positive patients without antiviral therapy, the intensity of correlation was moderate ( r = 0.564), which indicated that serum HBcrAg and HBsAg could not replace each other .…”

“…Though a positive correlation was reported between HBcrAg and HBsAg in HBeAg‐positive patients without antiviral therapy, the intensity of correlation was moderate ( r = 0.564), which indicated that serum HBcrAg and HBsAg could not replace each other . Additionally, serum HBcrAg and HBsAg had unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates of serum HBcrAg after HBsAg seroclearance, which decided the different possibilities for their applicability in clinical practice . Thus, a difference may exist between serum HBcrAg and HBsAg in reflecting intrahepatic cccDNA level.…”

“…Indeed, this finding was also highly consistent with the result of the correlation analysis. In previous studies, HBV genotypes, serum HBV DNA levels and liver histological changes were reported to be associated with the levels of serum HBcrAg, HBsAg or HBV RNA . However, they had no significant association with intrahepatic cccDNA levels among HBeAg‐positive patients in this study.…”

“…Hepatitis B core‐related antigen (HBcrAg) is a new valuable serum marker of HBV, and it consists of three species of related proteins sharing an identical 149 amino acid sequence: hepatitis B core antigen (HBcAg), hepatitis B e antigen (HBeAg) and a truncated 22 kDa precore protein (p22Cr) . Like HBeAg, p22cr is also a processed product of the precore protein, but with protein processing at both the N‐ and C‐terminals .…”