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Identification of a novel pre‐S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen
Author(s) -
YEH CHAUTING,
CHANG MEIHUI,
LAI HSINYU,
CHANG MINGLING,
CHU CHIAMING,
LIAW YUNFAN
Publication year - 2003
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2003.03146.x
Subject(s) - superinfection , hbsag , hepatitis b virus , medicine , virology , virus , hepatitis b , orthohepadnavirus , immunology
Background and Aim: The aim of the present study was to investigate whether spontaneous seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B could be attributed to the presence of pre‐S/S gene mutations. Methods: Of 34 hepatitis B virus (HBV) carriers who experienced spontaneous seroclearance of HBsAg, 30 were still seropositive for HBV DNA. The serum samples of these carriers were subjected to sequence analysis. Results: A novel pre‐S2 mutation, G149R , was found in nine (group I) but not in 17 (group II) patients carrying HBV DNA with intact pre‐S/S reading frames. In the remaining four patients (group III), only aberrant pre‐S/S transcripts were found in their sera. Distinct patterns of amino acid substitutions specific to group I and II patients were identified. Superinfection by hepatitis C or D virus occurred predominantly in group II patients ( P = 0.019). Superinfection by HBV of a different genotype occurred predominantly in patients without hepatitis C or D virus superinfection ( P = 0.013). Site‐directed mutagenesis experiments showed that secretion of HBsAg was not defective in the pre‐S2 G149R mutant. Conclusions: In a particular subgroup (group I) of patients, seroclearance of HBsAg was not caused by superinfection of other hepatitis viruses, nor was it caused by failure of HBsAg secretion or detection. Instead, a yet unrecognized mechanism associated with emergence of a novel pre‐S2 mutation is responsible.