Change of hepatitis B virus DNA and covalently closed circular DNA status in liver graft after liver transplantation.

Recurrence of hepatitis B virus (HBV) occurs despite prophylaxis, and covalently closed circular DNA (cccDNA) is thought to play a role owing to its resistance to prophylactic agents used. The aim of this study was to evaluate the changes of HBV DNA and cccDNA within the liver graft during liver transplantation (LT). Polymerase chain reaction (PCR) primers and probes were designed to measure total HBV DNA (tDNA) and cccDNA by real-time PCR. One hundred fifty samples from 70 patients who underwent LT for HBV were used for analysis. A 1st biopsy was taken from the donor before donor hepatectomy (Bx1), a 2nd from the recipient after reperfusion (Bx2), and a 3rd (Bx3) during follow-up after LT in 18 patients. Both tDNA and cccDNA after reperfusion were detected more frequently in pre-LT HBeAg(+) and high-HBV DNA titer recipients. However, the type and duration of antiviral agents and presence of mutation before LT did not influence the presence of tDNA or cccDNA in Bx2. tDNA positivity within the graft decreased from 41.4% to 22.2% during follow-up, but cccDNA did not (4.3% in Bx2 and 5.6% in Bx3). Although HBV recurrence was not related to pre-LT recipient HBeAg or HBV DNA titer, the presence of tDNA after reperfusion had strong correlation. The presence of tDNA within the graft is influenced by pre-LT viral replicative status, and although its presence decreases with prophylaxis, it is strongly correlated with recurrence. cccDNA does not have a role in predicting recurrence but is preserved within the graft despite prophylaxis.