HETEROGENEITY OF HEPATITIS-B VIRUS (HBV) CORE GENE IN A PATIENT WITH HBV-ASSOCIATED CIRRHOSIS AND SERUM NEGATIVITY FOR ANTI-HBC

Aims: We describe here the case of a patient suffering from severe chr onic hepatitis B associated with an unusual hepatitis B virus serology : HBsAg and HBeAg were both positive while anti-HBc was negative by ra dioimmunoassay. Methods: A very sensitive anti-HBc ELISA (IMx CORE) wa s performed and was able to detect anti-HBc sporadically throughout th e clinical course. Molecular characterization of hepatitis B virus str ains in this patient enabled us to explain this particular serological and clinical pattern of hepatitis B virus infection. Results: Hepatit is B virus genotype determined by size polymorphism of the core gene a nd the pre-S region was found to be D/E and consistent with the result s of serological subtyping (HBV ayw(2-4)). DNA sequence analysis of th e pre-C/C region showed the presence of significant nucleotide changes . In association with a wild type hepatitis B virus strain, we could d etect at least four hepatitis B virus variants with nucleotide deletio ns leading to a frameshift in the core gene. According to the position of the mutations, these hepatitis B virus core variants are expected to be defective for B-cell epitopes and T-H-cell epitopes. Conclusions : These mutations explain the low level production of anti-HBc antibod y. It is noteworthy that the absence of detectable anti-HBc in serum w as associated with severe liver damage, suggesting that the deficient humoral response to HBcAg was not accompanied by a cellular immune tol erance to HBc/eAg, the supposed target for cytotoxic T-cell lysis.