PRECORE MUTANT HEPATITIS-B VIRUS AND OUTCOME OF CHRONIC INFECTION ANDHEPATITIS IN HEPATITIS-B E-ANTIGEN-POSITIVE CHILDREN

Mutant hepatitis B virus (HBV), responsible for the lack of hepatitis B virus ''e'' antigen (HBeAg) secretion because of a translational sto p codon at nucleotide 1896 of the HBV-DNA precore region (HBeAg minus HBV), has been detected worldwide in acute and chronic HBV infections and diseases. HBeAg minus HBV appears to condition the outcome of infe ction and to be involved in the pathogenesis of hepatitis B. We invest igated the mutant prevalence and its clinical implications in 30 hepat itis B surface antigen/HBeAg-positive children (17 treated with interf eron) with chronic hepatitis B. Wild-type and HBeAg minus HBV were cha racterized by quantitative oligohybridization assays in sera from 29 c hildren followed up for a mean of 33 mo (12 mo to 9 y). At admission, 18 children (62%) circulated wild-type HBV alone; mutant HBV became de tectable in two of them during the follow-up before HBeAg/anti-HBe ser oconversion. Wild-type and HBeAg minus HBV were detected in 10 childre n (34.5%); mutant HBV levels were lower than 20% of total viremia in f our of them and higher in six. Serum HBV-DNA from one child did not hy bridize with our probes. HBeAg minus HBV was associated with older age (p < 0.009) and higher histologic activity (p < 0.069). HBeAg/anti-HB e seroconversion occurred independently from HBeAg minus HBV detection ; it was observed in six (37.5%) of 16 children with wild-type HBV alo ne and in four (33.3%) of 12 children with mixed viremia. In cases wit h mixed viremia, seroconversion occurred in four (66%) of six with HBe Ag minus levels lower than 20% of total viremia but in none of six wit h higher levels (p < 0.066). These findings suggest that HBeAg minus H BV can be detected in chronic HBV carrier children; it has relevant cl inical implications and affects the outcome of both HBV infection and disease when its relative prevalence reaches values higher than 20% of total viremia.