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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

Authors

  • CHAU-TING YEH,

    Corresponding author
    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
      Dr Chau-Ting Yeh, Liver Research Unit, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, Taiwan. Email: catyeh@ms14.hinet.net
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  • MEI-HUI CHANG,

    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
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  • HSIN-YU LAI,

    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
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  • MING-LING CHANG,

    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
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  • CHIA-MING CHU,

    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
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  • YUN-FAN LIAW

    1. Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan
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Dr Chau-Ting Yeh, Liver Research Unit, Chang Gung Memorial Hospital, 199, Tung Hwa North Road, Taipei, Taiwan. Email: catyeh@ms14.hinet.net

Abstract

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.

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