Detection of precore hepatitis B virus mutants in asymptomatic HBsAg-positive family members

Authors

  • Ulus Salih Akarca,

    1. Section of Gastroenterology, Tulane University Medical School and Veterans Administration Medical Center, New Orleans, Louisiana 70112
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  • Sheila Greene,

    1. Section of Gastroenterology, Tulane University Medical School and Veterans Administration Medical Center, New Orleans, Louisiana 70112
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  • Anna Suk Fong Lok M.D.

    Corresponding author
    1. Section of Gastroenterology, Tulane University Medical School and Veterans Administration Medical Center, New Orleans, Louisiana 70112
    • Tulane University Medical Center, Department of Medicine, Section of Gastroenterology, SL35, 1430 Tulane Avenue, New Orleans, LA 70112
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Abstract

Precore hepatitis B virus mutants have been detected mainly in HBeAg-negative patients with active liver disease. We previously reported two novel mutations: M1 (C-to-T change at nucleotide 1856 [pro-ser at codon 15]) and M3 (G-to-A change at nucleotide 1898 [gly-ser at codon 29]) in addition to two well-described mutations: M2 (G-to-A change at nucleotide 1896 [trp-stop at codon 28]); and M4 (G-to-A change at nucleotide 1899 [gly-asp at codon 29]) in Chinese patients. The aims of this study were to determine (a) the prevalence of precore HBV mutations in asymptomatic carriers and (b) whether family members share the same mutated sequence as the index patients. Fifty-three index patients and 89 HBsAg-positive family members were studied by means of direct sequencing of polymerase chain reaction–amplified hepatitis B virus DNA. M0, a conserved mutation (T-to-C at nucleotide 1858, codon 15), was detected in 81% and 12% family members of index patients with and without M0, respectively (p<0.0001). The clustering of M0 indicates that most subjects were infected through intrafamilial transmission. M1 was detected in all the family members of patients with M1 but in none of the family members of patients with wild-type or M2 sequences (p<0.0001). M2 was detected in 25%, 0% and 15% of family members of patients with M2, M1 and WT sequences, respectively (p=0.19). M3 was detected in five and M4 in four family members. M1 was equally distributed among HBeAg-positive and HBeAg-negative family members, 19.5% vs. 9% (p=0.34), whereas M2 was detected more frequently in HBeAg-negative family members: 45.5% vs. 4.5% in HBeAg-positive family members (p<0.0001). Ten (77%) of 13 family members with M2 and all 15 family members with M1 had normal serum aminotransferase levels. The family members with M2 were significantly older than those with wild-type or M1 sequences (mean ages, respectively, 37.9 ± 5,23 ± 1.4 and 24.1 ± 3yr;p=0.0005). In addition, M2 was more frequently detected in family members who were older than the index patients. Longitudinal studies documented progression from wild-type sequence to M2 in some family members, but progression from wild-type to M1 or M1 to M2 was not observed. Our data showed that precore HBV mutants can be detected in 33% asymptomatic carriers. M1 appears to be present at the onset of infection, whereas M2 emerges (from wild-type but not M1) during the course of infection. Initiation of infection with M2 only seems to be rare. (HEPATOLOGY 1994;19:1366–1370.)

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