NOVEL APPLICATION OF A POINT MUTATION ASSAY - EVIDENCE FOR TRANSMISSION OF HEPATITIS-B VIRUSES WITH PRECORE MUTATIONS AND THEIR DETECTION IN INFANTS WITH FULMINANT-HEPATITIS-B

Mutations of the precore region of hepatitis B virus (HBV) genome have been associated with fulminant and severe chronic hepatitis. However uncertainty remains about the clinical significance and transmissibili ty of these mutant strains. A point mutation assay (PMA) was developed to identify qualitatively and quantitatively mutations affecting prec ore amino acids 1 and 28. We have analysed serum samples from six moth er-infant pairs where perinatal transmission of HBV has occurred and w here the mothers were HBV carriers without detectable serum HBeAg. In three cases fulminant hepatitis developed in the infant, in two cases acute hepatitis resolved, and in one case the infant was immunised and did not become infected. We also examined serum from a healthcare wor ker, an anti-HBe-seropositive HBV carrier, believed to have transmitte d HBV infection to a patient. The PMA results were confirmed in;all ca ses by direct sequencing of polymerase chain reaction (PCR) products u sing nested and double-nested PCR with primers to the precore and X re gion. Precore aa28 mutant-type virus was detected in the serum of one mother at the time of delivery of three of her children, two of whom d eveloped fulminant hepatitis. Another mother of an infant with fulmina nt hepatitis had no precore mutations. In one mother-infant pair a mix ed viral population was found; the acute hepatitis B in the infant res olved. The HBV sequence from the healthcare worker was also of aa28 mu tant type. No mutations of aa1 were detected in any of the specimens. The study supports the association of precore mutations with some case s of transmission of HBV infection from HBeAg-negative mothers to thei r infants. Precore mutations may also be associated with fulminant hep atitis B in infants. Transmission of HBV infection from an HBeAg-negat ive healthcare worker may be associated with HBV precore mutation. (C) 1994 Wiley-Liss. Inc.