Identification of a novel pre-S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen
Article first published online: 19 SEP 2003
Journal of Gastroenterology and Hepatology
Volume 18, Issue 10, pages 1129–1138, October 2003
How to Cite
YEH, C.-T., CHANG, M.-H., LAI, H.-Y., CHANG, M.-L., CHU, C.-M. and LIAW, Y.-F. (2003), Identification of a novel pre-S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen. Journal of Gastroenterology and Hepatology, 18: 1129–1138. doi: 10.1046/j.1440-1746.2003.03146.x
- Issue published online: 19 SEP 2003
- Article first published online: 19 SEP 2003
- Accepted for publication 12 February 2003.
- hepatitis B surface antigen;
- hepatitis B virus;
- pre-S2 mutant;
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.