Heterogeneity of hepatitis B virus (HBV) core gene in a patient with HBV-associated cirrhosis and serum negativity for anti-HBc.
OBJECTIVE
We describe here the case of a patient suffering from severe chronic hepatitis B associated with an unusual hepatitis B virus serology: HBsAg and HBeAg were both positive while anti-HBc was negative by radioimmunoassay.


METHODS
A very sensitive anti-HBc ELISA (IMx CORE) was performed and was able to detect anti-HBc sporadically throughout the clinical course. Molecular characterization of hepatitis B virus strains in this patient enabled us to explain this particular serological and clinical pattern of hepatitis B virus infection.


RESULTS
Hepatitis B virus genotype determined by size polymorphism of the core gene and the pre-S region was found to be D/E and consistent with the results of serological subtyping (HBV ayw2-4). DNA sequence analysis of the pre-C/C region showed the presence of significant nucleotide changes. In association with a wild type hepatitis B virus strain, we could detect at least four hepatitis B virus variants with nucleotide deletions 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 TH-cell epitopes.


CONCLUSIONS
These mutations explain the low level production of anti-HBc antibody. It is noteworthy that the absence of detectable anti-HBc in serum was associated with severe liver damage, suggesting that the deficient humoral response to HBcAg was not accompanied by a cellular immune tolerance to HBc/eAg, the supposed target for cytotoxic T-cell lysis.
Hepatitis and AIDS Research Unit, Lyon, France.
F
F
Zoulim
X
X
Zhang
C
C
Pichoud
C
C
Trepo
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D002872:Chromosome Deletion; D002908:Chronic Disease; D018740:Genetic Heterogeneity; D006509:Hepatitis B / Q000150:complications*; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data
D000914:Antibodies, Viral; D015415:Biomarkers; D006512:Hepatitis B Core Antigens