Clinical evaluation of hepatitis B core-related antigen in chronic hepatitis B and hepatocellular carcinoma patients

Clin Chim Acta. 2018 Nov:486:237-244. doi: 10.1016/j.cca.2018.07.027. Epub 2018 Jul 17.

Abstract

Background: Hepatitis B core-related antigen (HBcrAg) has been revealed as an important marker of Hepatitis B virus (HBV) infection recently. We aimed to evaluate the HBcrAg assay for indication of HBV loads in chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients and assess the association between HBcrAg/cccDNA and HCC recurrence.

Methods: HBcrAg was measured by chemiluminescence enzyme immunoassay. Intrahepatic covalently closed circular DNA (cccDNA) was measured by real-time PCR with TaqMan fluorescent probes based on liver specimens from 89 HCC patients.

Results: HBcrAg correlated positively with HBV DNA irrespective of HBeAg status. Both HBcrAg and HBV DNA were associated with cccDNA in patients with elevated serum HBV DNA (>4 log IU/mL). In patients with non-elevated HBV DNA (≤4 log IU/mL), no relationship between HBV DNA and cccDNA was observed, but we still documented a modest correlation between HBcrAg and cccDNA. Finally, the recurrence-free survival rates were significantly lower in HCC patients with high intrahepatic cccDNA and serum HBcrAg levels than those with low cccDNA/HBcrAg levels (p = 0.035, p = 0.003 respectively).

Conclusions: HBcrAg not only can serve as a biomarker to assess HBV loads in patients as well as provide a good method for monitoring cccDNA in HCC, but also can be used as a good prognostic predictor for HCC patients.

Keywords: Chronic hepatitis B (CHB); Covalently closed circular DNA (cccDNA); Hepatitis B core-related antigen (HBcrAg); Hepatitis B virus (HBV) DNA; Hepatocellular carcinoma (HCC).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Cohort Studies
  • DNA, Viral / blood
  • DNA, Viral / genetics*
  • Female
  • Fluorescent Dyes / chemistry
  • Hepatitis B Core Antigens / blood
  • Hepatitis B Core Antigens / genetics*
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Luminescence
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Biomarkers
  • DNA, Viral
  • Fluorescent Dyes
  • Hepatitis B Core Antigens