Elimination of hepatitis B virus surface antigen and appearance of neutralizing antibodies in chronically infected patients without viral clearance

Summary.  Seroconversion from hepatitis B surface antigen (HBsAg) to antibodies against HBsAg (anti-HBs) usually indicates resolution of hepatitis B virus (HBV) infection. Here, two HBV-infected patients with seroconversion to anti-HBs were found to be persistently positive for HBeAg and HBV DNA. Immunohistology of liver biopsies confirmed the expression of HBV proteins in the liver of one patient. The neutralizing ability of anti-HBs in patient sera was demonstrated by blocking HBV infection of primary tupaia hepatocytes. Analysis of the HBsAg-encoding region of HBV isolates from patients indicated the coexistence of heterogeneous HBV genomes in patients. The majority of recombinant variant HBsAg was reactive in HBsAg assays and was able to bind to anti-HBs. Circulating immune complexes (CIC) of HBsAg in patient sera could be detected by polyethylene glycol precipitation and trypsin digestion. Thus, neutralizing anti-HBs may appear in chronic HBV carriers for long periods but does not necessarily lead to complete viral clearance.