Association of mutations in the core promoter and precore region of hepatitis virus with fulminant and severe acute hepatitis in Japan

Authors

  • TOMOYUKI ARITOMI,

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
    2. †The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
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  • HIROSHI YATSUHASHI,

    Corresponding author
    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
    • Hiroshi Yatsuhashi, Institute for Clinical Research, Nagasaki Chuo National Hospital, WHO Collaborating Center for Reference and Research on Viral Hepatitis, Kubara 2-1001-1 Omura, Nagasaki-ken 856–0835, Japan. Email: ncnhyano@nagasaki-noc.or.jp

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  • TATSUYA FUJINO,

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
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  • KAZUMI YAMASAKI,

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
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  • OSAMI INOUE,

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
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  • MICHIAKI KOGA,

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
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  • YUJI KATO,

    1. †The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
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  • MICHITAMI YANO

    1. *Institute for Clinical Research, Nagasaki Chuo National Hospital and WHO Collaborating Center for Reference and Research on Viral Hepatitis
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Abstract

It was recently reported that mutations in the precore and core promoter region of hepatitis B virus (HBV) are associated with fulminant hepatitis. The aim of this study was to investigate the association of mutations in the precore and core promoter region of HBV with fulminant and severe acute hepatitis. We studied Japanese patients with acute HBV infection, including seven patients with fulminant hepatitis, 12 with severe acute hepatitis and 41 with acute self-limited hepatitis. The presence of HBV mutants was examined by using a point mutation assay to detect a G to A transition at position 1896 in the precore region and an A to T transition at position 1762 and a G to A transition at position 1764 in the core promoter region. Significant differences in the proportion of mutations in the precore or core promoter region were present between patients with fulminant hepatitis and self-limited acute hepatitis (7/7 (100%) vs 4/41 (9.8%), P < 0.01) and between severe acute hepatitis and self-limited acute hepatitis (6/12 (50.0%) vs 4/41 (9.8%), P < 0.01). The frequency of mutation increased proportionately with the severity of disease in patients with acute HBV infection. Fulminant hepatitis B in Japan is closely associated with mutations in the core promoter and precore gene of HBV. Point mutation assays for HBV precore and core promoter analysis may be useful to predict the outcome of liver disease in patients with acute HBV infection.

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