Mutations at the Gene Encoding the 'a' Determinant of HBsAg in Chronic Hepatitis B Patients with Concurrent HBsAg and Anti-HBs Positivity

Park, Joong won; Yoon, Jung Hwan; Hwang, You Jin; Lee, Hyo Suk; Kim, Chung Yong

Abstract

BACKGROUND/AIMS: A humoral escape mutant of hepatitis B virus(HBV) having mutations at HBsAg a' determinant has been found in patients with concurrent HBsAg and anti-HBs in sera. This study was undertaken to investigate whether such a variant was involved in Korean patients with chronic hepatitis B,
METHODS
We conducted an analysis of sequences of DNA encoding the HBsAg a' determinant in six chronic hepatitis B patients with concurrent HBsAg an6 anti-HBs positivity, and in three HBsAg-positive controls without anti-HBs in sera. One of the six cases 4ad received long-term hepatitis B immunoglobulin treatment after liver transplantation and five were chronic hepatitis B patients with naturally occurring concurrent HBsAg and anti-HBs. HBV DNA extracted from sera of nine patients was amplified and sequenced within the S gene encoding the a' determinant.
RESULTS
HBVs from three controls had no rnutations in the a determinant. Six patients with concurrent HBsAg and anti-HBs had point mutations in the S gene encoding the a' determinant. A liver-transplanted patient had substitutions at nucleotide 587(arginine for glycine at aa 143) and nucleotide 561(tyrosine for serine at aa 136) of the S gene. All of the five patients with naturally occurring concurrent HBsAg and anti-HBs had a substitution at nucleotide 531(serine for isoleucine at aa 126) and four of five had substitutions at nucleotile 546 and 552(asparagine for threonine at aa 131 and threonine for methionine at aa 133). One case had three consecutive substitutions at nucleotide 554, 555, 556(arginine for phenylalanine at aa 134).
CONCLUSIONS
These results demonstrated the presence of mutations at HBsAg a detenninant in Korean chronic hepatitis B patients with concurrent HBsAg and anti-HBs.