Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen

Authors

  • Hiroyuki Marusawa,

    1. Division of Gastroenterology and Hepatology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Shinji Uemoto,

    1. Division of Transplantation Immunology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Makoto Hijikata,

    1. Laboratory of Human Tumor Viruses, Department of Viral Oncology, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Yoshihide Ueda,

    1. Division of Gastroenterology and Hepatology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Koichi Tanaka,

    1. Division of Transplantation Immunology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Kunitada Shimotohno,

    1. Laboratory of Human Tumor Viruses, Department of Viral Oncology, The Institute for Virus Research, Kyoto University, Kyoto, Japan
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  • Tsutomu Chiba M.D.

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan
    • Division of Gastroenterology and Hepatology, Department of Medicine, Postgraduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. fax: (81) 75-751-4303
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Abstract

Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti-HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti-HBc–positive healthy individuals. HBV DNA was detectable in 13 of 14 healthy donors who were positive for both anti-HBc and antibodies to hepatitis B surface antigen (anti-HBs), but in none of 3 who were positive for anti-HBs alone. The detected HBV genomes from these subjects included covalently closed circular DNA and pregenomic RNA, the replication intermediate of HBV. Notably, 5 of 7 cases tested were predominantly infected with wild type HBV strains without any mutations in the precore and core promoter regions under the presence of circulating antibody to hepatitis B e antigen. Interestingly, a predominant clone detected in one donor showed a 63-nucleotide deletion in the precore region including an encapsidation signal sequence. Our findings indicate that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied by ongoing viral replication and few nucleotide mutations in the precore and core regions.

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