Fulminant reactivation of hepatitis B due to envelope protein mutant that escaped detection by monoclonal HBsAg ELISA

The detection of a fatal case of reactivation of hepatitis B, in a previously vaccinated Indonesian aptient after withdrawal of chemotherapy for lymphoma, was delayed because HBsAg was negative in a widely used monoclonal- antibody-based ELISA. The serum was later found to be strongly reactive for HBsAg by the polycional radioImmunoassay and for HBV DNA. PCR sequencing revelated a substitution of arginine for glycine at position 145 of HBsAg in the major neutralising epitope cluster, the a determinant, as well as a 2–aminoacid insertion of asparagine and theronine between positions 122 and 123, immediately upstream of this determinant.