FAMILIAL CLUSTERING OF HBV PRE-C AND PRE-S MUTANTS

Background/Aims: Little is known about the persistence and risk of inf ection with hepatitis B viruses (HBV) containing mutations in the pre- C and pre-S region, The aim of this study was to study the long-term p ersistence and the risk of intrafamilial spreading of these variants. Methods: Serological markers were analyzed immunologically and pre-C a nd pre-S sequences of HBV DNA in sera from several members of five fam ilies by DNA amplification and direct sequencing. Results: In most HBV -DNA positive individuals of each family, either the dominant HBV popu lation or a subpopulation had a stop codon in the pre-C region which p revented expression of e-antigen, The pre-S region of the dominant vir us populations of 8/15 HBV-DNA positive sera showed different deletion s or a pre-S2 translation initiation codon mutation in addition to var ious point mutations. Selection for pre-C and pre-S mutant viruses fro m a predominant ''wildtype'' virus population was observed in three in dividuals during the natural course of infection. Persistence of a pre -C/pre-S double mutant virus as a stable strain for 6 years was found in one patient. Conclusions: These data indicate extensive intrafamili al clustering of HBV variants with mutations in the pre-C and pre-S re gions due to patient-specific selection mechanisms and long-term persi stence of some mutants as stable strains, The type of viruses found su ggests that occasionally virus subpopulations are selectively transmit ted or become a dominant virus population after selection.