Correlation between risk of hepatitis B virus recurrence and tissue expression of covalently closed circular DNA in living donor liver transplant recipients treated with high-dose hepatitis B immunoglobulin

Transplant Proc. 2014 Dec;46(10):3548-53. doi: 10.1016/j.transproceed.2014.06.074.


Background and aims: Despite the application of prophylaxis, the risk of hepatitis B virus (HBV) recurrence remains. However, actual mechanism(s) and definite risk factor(s) are obscure. The present study examined the correlation between the HBV load in liver explants and post-liver transplant (OLT) HBV recurrence.

Methods: HBV DNA was extracted from liver tissue taken from 50 living donor OLT (LDLT) patients using the QuickGene DNA Tissue Kit S (Fujifilm, Tokyo, Japan) and subjected to real-time polymerase chain reaction with the following primers: 5'-CACATGGCCTCCAAGGAGTAA-3' (forward primer) and 5'-TGAGGGTCTCTCTCTTCCTCTTGT-3' (reverse primer). To prevent HBV infection, patients were treated daily with high-dose (10,000 IU) hepatitis B immunoglobulin (HBIG) for the first week after LDLT. They then received weekly doses for the next month and then monthly doses for ≤1 year. If the anti-hepatitis surface antigen antibody titer was <1,000 IU/L, an antiviral agent (AVA) was added to the regimen.

Results: The mean (±SD) tissue HBV DNA and covalently closed circular DNA (cccDNA) loads were -0.8 ± 1.2 (range, -2.9 to 2.6) and -2.3 ± 1.1 (range, -4.6 to 0.6) log10 copies/cell, respectively. There was a significant correlation between serum and tissue HBV DNA (r = 0.65; P = .00) and cccDNA concentrations (r = 0.55; P = .00). Six patients suffered HBV recurrence and 9 required additional AVA. There was no direct correlation between HBV recurrence and tissue cccDNA concentration. However, the concentration of cccDNA was significantly greater those patients suffering recurrence and receiving AVA treatment (high-risk group).

Conclusion: High tissue cccDNA concentrations may be a risk factor for HBV recurrence despite high-dose HBIG prophylaxis.

MeSH terms

  • Adult
  • Aged
  • DNA, Circular / genetics*
  • DNA, Viral / analysis*
  • Female
  • Hepatitis B / drug therapy*
  • Hepatitis B / epidemiology
  • Hepatitis B / virology
  • Hepatitis B virus / genetics*
  • Humans
  • Immunization, Passive
  • Immunoglobulins / administration & dosage*
  • Incidence
  • Japan / epidemiology
  • Liver Transplantation*
  • Living Donors*
  • Male
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Recurrence
  • Republic of Korea / epidemiology
  • Risk
  • Transplant Recipients


  • DNA, Circular
  • DNA, Viral
  • Immunoglobulins
  • hepatitis B hyperimmune globulin