Evolution of precore/core promoter mutations in hepatitis B carriers with hepatitis B e antigen seroreversion

Authors

  • Chun-Jen Liu,

    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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  • Pei-Jer Chen,

    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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  • Ming-Yang Lai,

    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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  • Prof. Jia-Horng Kao,

    Corresponding author
    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    • Director, Hepatitis Research Center, National Taiwan University Hospital, 1 Chang-Te St., Taipei 100, Taiwan.
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  • Ding-Shinn Chen

    1. Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
    2. Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
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Abstract

The evolution of precore stop codon mutation (A1896) and dinucleotide mutation (T1762/A1764) in the basic core promoter (BCP) of hepatitis B virus (HBV) genome during transient seroconversion and seroreversion of hepatitis B e antigen (HBeAg) remains unclarified. Five HBeAg-positive HBV carriers who experienced transient seroconversion followed by seroreversion of HBeAg (Group I, 3.3%) and 3 HBeAg-negative HBV carriers with documented reversion of HBeAg (Group II, 2.5%) in a prospective cohort of 272 patients with chronic hepatitis B were thus identified. The sequential changes at the precore nucleotide 1896 and BCP dinucleotide 1762/1764 were determined by polymerase chain reaction and direct sequencing. At enrollement, precore A1896 and BCP T1762/A1764 were noted in 4 (50%) and 1 (13%) of the eight patients. During a median follow-up period of 58 months (range: 31–76 months), 12 episodes of transient HBeAg seroconversion followed by seroreversion were encountered in Group I patients and 3 episodes of HBeAg seroreversion in Group II patients. Accompanying acute exacerbations were found in two-thirds of patients with either HBeAg seroconversion or seroreversion. Overall, precore nucleotide A1896 remained identical in 73% and 83% of the seroconversion and seroreversion events, respectively. BCP dinucleotide T1762/A1764 remained unchanged in 94% and 92% of the seroconversion and seroreversion events, respectively. At the end of follow-up, only one had both precore and BCP mutations. In conclusion, these data suggested that HBeAg seroreversion might be due to the lack of sustained precore and BCP mutations after HBeAg seroconversion. Although uncommon, HBeAg seroreversion can be associated with hepatitis exacerbation. J. Med. Virol. 74:237–245, 2004. © 2004 Wiley-Liss, Inc.

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