Conserved core protein sequences in hepatitis B virus infected patients without anti-HBc

The absence of detectable anti-HBc antibodies in some hepatitis B virus (HBV) infected patients may be due to altered core-protein (HBc) sequences. To investigate this possibility we sequenced the pre-C/C-region of HBV isolated from 12 juvenile cancer patients who incurred a nosocomial infection of HBV during chemotherapy but did not develop anti-HBc antibodies or acute cytolytic episodes. The sequences demonstrated the highest sequence homology to the pre-C/C region of a previously cloned HBV genome (subtype ayw) and no deletions or striking mutations were detected. Up to 7 years after infection almost all the survivors developed low titers of anti-HBc antibodies but no clinical signs of hepatic damage. These results suggest that chemotherapy may induce a tolerance status to HBcAg, the most immunogenic HBV protein.