Mutations in the basic core promotor and the precore region of hepatitis Bvirus and their selection in children with fulminant and chronic hepatitisB

The involvement of precore stop codon 1896-A and base exchanges in the AT-r ich region at positions 1762 and 1764 of the hepatitis B core promotor has been controversely discussed in adults with fulminant hepatitis B, Because no data are currently available on children, we analyzed the basic core pro motor (BCP) and precore region in children with chronic and fulminant hepat itis B, The BCP and precore region were sequenced directly and after clonin g from mothers and infants. Thirteen children suffered from chronic liver d isease, 6 of whom were treated with interferon alfa (IFN-a). All 13 patient s seroconverted from hepatitis B e antigen (HBeAg) to hepatitis B e antigen antibodies (anti-HBe), and sera were analyzed before and after seroconvers ion. Nine vertically infected infants developed a fulminant course of hepat itis B, The occurrence of BCP (1762-T/1764-A, 7.7%) and precore (1896-A, 7. 7%; 1899-A, 15%) mutations in chronic hepatitis B was rare. A genotype shif t from D to A was observed in 3 patients after development of anti-HBe. A h igh number of base exchanges was detected in those infants with fulminant h epatitis B. Eight of nine showed a G-A exchange at positions 1896/97 (89%), 1899 (56%), and/or mutations at nucleotide (nt) positions 1762 (56%) and 1 764 (78%). All virus strains belonged to genotype D, whereas in the only su rviving infant, a D-to-A shift was detected. Hepatitis B virus (HBV) DNA cl ones were examined from 3 babies and 5 mothers. Our results showed a hetero geneous virus population in 4 of 5 mothers. In contrast, a homogeneous viru s population emerged in the infants. According to our data, the analysis in children with fulminant and chronic hepatitis B revealed a striking presen ce of BCP and precore mutants in infants with fulminant hepatitis (FH) when compared with clinically inapparent anti-HBe-positive children (P < .002), which could be one factor in the pathogenesis of fulminant hepatitis B in children.