Configuration and replication competence of hepatitis B virus DNA in peripheral blood mononuclear cells from chronic hepatitis B patients and patients who have recovered from acute self-limited hepatitis

Several studies have reported the presence of hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). However, the mode of existence, infectivity and replication competence of HBV DNA in PBMCs remain unclear. To clarify these questions, we assayed for covalently closed circular DNA (cccDNA) and integrated HBV DNA in PBMCs from ten patients who had recovered from acute self-limited hepatitis B (AHB) and 14 chronic hepatitis B (CHB) patients. HBV DNA was detected in all six CHB patients who were positive for hepatitis B e antigen (eAg), and cccDNA was detected in five. HBV DNA was detected in seven of the eight CHB patients who were negative for eAg, and cccDNA was detected in three. HBV DNA and cccDNA was also detected in five and two of the ten AHB patients, respectively. Integrated HBV was not detected in PBMCs of any patients. HBV DNA presence and replication competence in PBMCs are associated with eAg-positive phenotype. Sequence analysis revealed that the source of HBV DNA differed between PBMCs and serum. Even in patients who have recovered from AHB, replicable HBV may persist in PBMCs.