SELECTION OF A PRECORE MUTANT AFTER VERTICAL TRANSMISSION OF DIFFERENT HEPATITIS-B VIRUS VARIANTS IS CORRELATED WITH FULMINANT-HEPATITIS ININFANTS

The incidence of perinatal transmission of hepatitis B virus (HBV) dep ends on the HBeAg/anti-HBe status of the mother. While children of HBe Ag-positive mothers have a 90% probability of acquiring a chronic hepa titis B virus carrier state, babies of anti-HBe-positive mothers are m ore likely to develop fulminant hepatitis within the first 3 to 4 mont hs of life. There is evidence that precore (pre-C) mutations of the HB V can be associated with fulminant hepatitis. The pre-C region was the refore examined in sera from nine infants with fulminant hepatitis aft er vertical transmission, one HBeAg-positive and seven anti-HBe-positi ve mothers by polymerase chain reaction (PCR) and direct sequence anal ysis. In five mother/infant pairs the virus populations were character ized in addition by analysing clones of the amplified products. All mo thers were infected with two or four variants of HBV with mutations at different positions of the preC genome including position 1896, which results in a stop codon. While the precore stop codon was detected in a portion of the virus populations of the HBeAg-positive and of four anti-HBe-positive mothers the dominating viral strain was represented by the wild type virus in three. In contrast, the virus populations of all babies showed the 1896 precore variant as the prevalent virus str ain during the phase of active disease. In the surviving baby only wil d type sequences were detected after recovery. Subtype ayw was found i n all mothers and infants and adw2 was present in three mothers and in the surviving child. The findings suggest that all mothers carried a wild type HBV population with a certain number of different HBV varian ts. After transmission of the mixed virus population a selection proce ss was started in the baby. The association of sub-type ayw with the p recore mutations and with the fatal outcome of the hepatitis B might b e the result of a directed selection of this variant with a particular advantage in the viral life cycle. (C) 1995 Wiley-Liss, Inc.