Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg

Background/Aims: The persistence of serum and liver hepatitis B virus (HBV) sequences in patients with chronic hepatitis B after loss of HBsAg has already been described, We have attempted to elucidate the significance of these HBV sequences after loss of HBsAg. Methods: Fifteen patients were studied, We looked for serum and liver HBV DNA, using polymerase chain reaction (PCR) with different sets of primers and ill situ hybridization. The sedimentation velocity of serum HBV DNA was measured on a gradient of sucrose in two patients. Results: Serum HBV DNA was detected by PCR in four of the 14 patients tested at 0 months after loss of HBsAg, two patients remained HBV DNA positive until 12 months, and none was positive at 24 months. The sedimentation velocity of serum HBV DNA in sucrose was relatively similar to that of a chronic HBV carrier with active viral replication. Liver HBV DNA was demonstrated by PCR in all 15 patients and by in situ hybridization in six patients. Conclusions: Our results show that: 1) HBV DNA may persist in the serum in a minority of patients and may be associated with circulating viral particles; 2) HBV DNA persists in the liver in all patients and its extrachromosomal localization was shown by in situ hybridization technique in some cases. These results suggest the persistence of low-level HBV replication after loss of HBsAg.