Previous studies have suggested that serum hepatitis B core-related antigen (HBcrAg) reflect the intrahepatic covalently closed circular (ccc) DNA levels. The authors were interested in the correlation of HBcrAg with serum and intrahepatic viral markers and liver histology. They measured HBcrAg using chemiluminescent enzyme immunoassay in 130 (36 HBeAg+ and 94 HBeAg-) biopsy-proven, untreated, patients with chronic hepatitis B. These HBcrAg levels were then correlated with: a) serum hepatitis B virus (HBV) DNA, quantitative HBsAg and ALT levels; b) intrahepatic total (t)HBV DNA, cccDNA, pregenomic (pg)RNA and cccDNA transcriptional activity (defined as pgRNA/cccDNA ratio); c) fibrosis and necroinflammatory activity scores. The authors found that HBcrAg levels were significantly higher in HBeAg+ vs. HBeAg- patients and correlated with serum HBV DNA, intrahepatic tHBV-DNA, pgRNA and cccDNA levels, and transcriptional activity. Patients who were negative for HBcrAg (<3 LogU/ml) had less liver cccDNA and lower cccDNA activity than the HBcrAg+ group. The authors also used principal component analysis with unsupervised clustering to identify that in a subgroup of HBeAg- patients, higher HBcrAg levels were associated with higher serum HBV DNA, intrahepatic tHBV-DNA, pgRNA, cccDNA transcriptional activity and with higher fibrosis and necroinflammatory activity scores. Therefore HBcrAg can be used as a surrogate marker of both intrahepatic cccDNA and its transcriptional activity.
Read more here