Significance of hepatitis B virus core-related antigen and covalently closed circular DNA levels as markers of hepatitis B virus re-infection after liver transplantation

J Gastroenterol Hepatol. 2013 Jul;28(7):1217-22. doi: 10.1111/jgh.12182.


Background and aim: Currently, hepatitis B virus (HBV) re-infection after liver transplantation (LT) can be almost completely suppressed by the administration of HBV reverse transcriptase inhibitors and hepatitis B immunoglobulins. However, after transplantation, there is no indicator of HBV replication because tests for the serum hepatitis B surface antigen and HBV-DNA are both negative. Therefore, the criteria for reducing and discontinuing these precautions are unclear. In this study, we examined the serum HBV core-related antigen (HBcrAg) and intrahepatic covalently closed circular DNA (cccDNA) in order to determine if these could be useful markers for HBV re-infection.

Methods: Thirty-one patients underwent LT for HBV-related liver disease at Nagasaki University Hospital from 2001 to 2010. Of these, 20 cases were followed up for more than 1 year (median follow-up period, 903 days). We measured serum HBcrAg and intrahepatic cccDNA levels in liver tissue. In addition, in nine cases, we assessed the serial changes of HBcrAg and intrahepatic cccDNA levels from preoperative periods to stable periods.

Results: We examined serum HBcrAg and intrahepatic cccDNA levels in 20 patients (35 samples). HBcrAg and cccDNA levels were significantly correlated with each other (r = 0.616, P < 0.001). From a clinical aspect, the fibrosis stage was significantly lower in both HBcrAg- and cccDNA-negative patients than in HBcrAg- or cccDNA-positive patients.

Conclusions: HBcrAg and cccDNA were useful as HBV re-infection markers after LT. Keeping patients' HBcrAg and cccDNA negative after LT might contribute to long-term graft survival.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • DNA, Circular / analysis*
  • DNA, Viral / analysis*
  • End Stage Liver Disease / etiology
  • End Stage Liver Disease / surgery*
  • Female
  • Graft Survival
  • Hepatitis B / complications
  • Hepatitis B / diagnosis*
  • Hepatitis B / prevention & control
  • Hepatitis B Core Antigens / blood*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / immunology
  • Humans
  • Liver / metabolism*
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Secondary Prevention


  • Biomarkers
  • DNA, Circular
  • DNA, Viral
  • Hepatitis B Core Antigens