Hepatitis B virus C gene heterogeneity in a familial cluster of anti-HBc negative chronic carriers.

We studied a familial cluster of adult HBV chronic carriers characterized by serological markers of active viral replication, normal or slightly elevated ALT levels and, in four out of five cases, absence of anti-HBc reactivity. The nucleotide sequence of the pre-C/C region of HBV was analyzed in three patients, showing the presence of wild-type HBV sequences accompanied by different deleted molecules. Some of the variant genomes were able to encode proteins retaining HBcAg and/or HBeAg reactivity, whereas others contained deletions leading to the synthesis of truncated proteins that could not be immunoprecipitated by anti-HBc or anti-HBe mono- and polyclonal antibodies. Defective molecules encoded by the variant C gene sequences might play a role in the determination of the clinical profile observed in the analyzed patients.