Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage.
Hepatitis B e antigen (HBeAg) is considered to be a major target for the immune response in chronic hepatitis B. The G-->A mutation at nucleotide 1896 may mediate viral escape by creating a TAG stop codon in the precore region, thus preventing HBeAg production. This mutation frequently evolves during HBe seroconversion if thymine, but rarely if cytosine, is present in position 1858. Applying a combination of polymerase chain reaction (PCR) and restriction enzyme action, we have studied the relation of the TAG mutation and the nucleotide (nt) 1858 variants to liver damage assessed by histology activity index (HAI) scoring in 175 chronic hepatitis B virus (HBV) carriers. A TAG mutation was found in 68 of 71 (96%) of HBeAg-negative carriers infected with a T-1858 strain, but not in any of 33 carriers infected exclusively with a C-1858 strain. Four patients showed a mutation of the precore start codon, and 2 had a TAA stop mutation at codon 2. HBeAg-positive infection with a mixture of wild-type and TAG mutant virus indicated active liver damage, because 8 of 9 (89%) of such patients had a Knodell HAI greater than or equal to 8. In HBeAg-negative stage, both inflammation and fibrosis were more pronounced in carriers infected with wild-type HBV compared with precore mutants. C-1858 strains were associated with more inflammation and fibrosis compared with T-1858 strains. C-1858 strains were found in 71% of northern European, 17% of southern European, 31% of African, 2% of Middle Eastern, and 10% of Far Eastern carriers. Analysis of these variants and mutants may prove useful for clinical evaluation and choice of therapy, and may be facilitated by the methods described.
Lindh
M
M
Department of Clinical Virology, Göteborg University, Sweden.
Horal
P
P
Dhillon
A P
AP
Furuta
Y
Y
Norkrans
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002353:Carrier State; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000473:pathology*; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D015335:Molecular Probes