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

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 [proser 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.(ABSTRACT TRUNCATED AT 250 WORDS)