Acute self-limiting hepatitis B after immunoprophylaxis failure in an infant

The occurrence of acute hepatitis after failure of immunoprophylaxis in cas es of mother-to-infant transmission of hepatitis B virus (HBV) is uncommon. Because immunoprophylaxis failure is caused by the emergence of an "a" det erminant escape mutant, the infants usually become HBV carriers. To evaluat e whether mutations in the S gene coding for the surface protein that conta ins the "a" determinant are associated with acute hepatitis after immunopro phylaxis failure, HBV DNA of an infant in with acute hepatitis developed wi th seroconversion to anti-HBs antibodies at 12 months of age despite admini stration of anti-hepatitis B immunoglobulin and hepatitis B vaccine was ana lyzed. The S gene from HBV DNA isolated from the serum of the infant at 12, 19, and 27 months of age was cloned and sequenced. Mutations affecting ami no acid residues in the first loop within the "a" determinant (codons 124-1 47) were found at 12 months of age. Moreover, a novel deletion mutant, with a 1-bp deletion at nucleotide 449 of the S gene, was found at 19 and 27 mo nths of age. This deletion resulted in a frame shift and it introduced a st op codon (TAG) at codon 176. Because the open reading frame of the S gene i s completely overlapped by the polymerase gene, mutations in the S gene may affect the polymerase gene. Based on this case, this study suggests that t he observed frame-shift mutation in the S gene might affect the polymerase protein and induce prompt suppression of viral replication. (C) 2002 Wiley- Liss, Inc.