Prevalence of precore‐defective mutant of hepatitis B virus in HBV carriers

Abstract

Two hundred and seventy-three serum specimens from hepatitis B virus (HBV) carriers were examined for the presence of a characteristic one point mutation at nucleotide (nt) 1896 from the EcoRI site of the HBV genome in the precore region (the preC mutant) using restriction fragment length polymorphism (RFLP) analysis. This assay approach could detect preC mutants or wild-type sequences when either form constituted more than 10% of the total sample. Overall, 65.5% (76/116) of HBeAg-positive carriers had only the preC wild-type. All HBeAg-positive asymptomatic carriers (n = 14) had only the preC wild-type. In patients with chronic hepatitis B and in anti-HBe-positive asymptomatic carriers, increased prevalence of the preC mutant was associated with the development of anti-HBe antibodies and normalization of the serum alanine aminotransferase concentration. Furthermore, 27 (29.0%) of 93 HBeAg-negative carriers had unexpectedly preC wild-type sequences only. Direct sequencing of the HBV precore region of HBV specimens from 24 patients revealed no mutation at nt 1896, supporting the specificity of the RFLP analysis. These results suggest that RFLP analysis was accurate for the detection of the preC mutation and that the absence of serum HBeAg cannot be explained solely by the dominance of the preC mutant.

Epidemiology of precore mutants of hepatitis B in the United Kingdom

“…These results are not unexpected as a small proportion of carriers, estimated to be about 3%, undergo seroconversion to anti-HBe each year [Hoofnagle et al, 1981;Viola et al, 1981;Anderson and Murray-Lyon, 1985]. These findings also fit with previous studies where between 0% and 34% of HBeAg positive carriers have been found to have codon 28 variants [Brunetto et al, 1991;Niitsuma et al, 1995;Fujiwara et al, 1998; Cabrerizo et al, 1998; Nagasaka et al, 1998; Knoll et al, (Tables III and V). In other patients variants may emerge but fail to be associated with high levels of virus replication (Table IV).…”

“…These figures compare well with a study from Germany [Knoll et al, 1999] where 52% (44/84) of their PCR positive HBeAg negative patients had recognised precore variants. Other groups, however, have reported from 23% to 100% HBeAg negative carriers with precore variants [Brunetto et al, 1991;Niitsuma et al, 1995;Fujiwara et al, 1998;Cabrerizo et al, 1998;Nagasaka et al, 1998]. The differences between the data probably reflect the different ethnic origins and therefore different genotypes within the study populations.…”

Clinical Significance of Genotypes and Precore/Basal Core Promoter Mutations in HBV Related Chronic Liver Disease Patients in North India

“…In agreement with Nittsuma et al and Gandhe et al, a precore mutant can not be the principal factor responsible for the absence of HBeAg [10,42]. A majority of HBeAg positive pediatric patients from Spain carried a mixture of precore wild type and mutant viruses (50 out of 60) [43].…”

Risk and Management of Blood-Borne Infections in Health Care Workers

“…The prevalence of these precore mutations in persons in the United States is unknown. The prevalence may be relatively high in certain parts of the world (41,124,171,173,197).…”