Sustained and focused hepatitis B virus nucleocapsid–specific T-cell immunity in liver transplant recipients compared to individuals with chronic and self-limited hepatitis B virus infection

Authors

  • Florian Bihl,

    1. Division of Gastroenterology and Hepatology, University Hospital of Geneva, Geneva, Switzerland
    2. Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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    • These authors contributed equally to this study.

  • Elisabetta Loggi,

    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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    • These authors contributed equally to this study.

  • John V. Chisholm III,

    1. Division of Gastroenterology and Hepatology, University Hospital of Geneva, Geneva, Switzerland
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    • These authors contributed equally to this study.

  • Maurizio Biselli,

    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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  • Maria C. Morelli,

    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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  • Carmela Cursaro,

    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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  • Norah A. Terrault,

    1. Department of Medicine and Gastroenterology, University of California, San Francisco, San Francisco, CA
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  • Mauro Bernardi,

    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
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  • Antonio Bertoletti,

    1. Singapore Institute for Clinical Science, Agency for Science Technology and Research, Singapore
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  • Pietro Andreone,

    Corresponding author
    1. Department of Internal Medicine, Cardioangiology and Hepatology, Azienda Ospedaliera Universitaria, Policlinico Sant'Orsola-Malpighi, Bologna, Italy
    • Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
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    • Telephone: 39.051.6363618; FAX: 39.051.345806

  • Christian Brander

    1. Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Abstract

Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is associated with poor graft- and patient-survival. Treatment with HBV-specific immunoglobulins (HBIG) in combination with nucleos(t)ide analogs is effective in preventing HBV reinfection of the graft and improving OLT outcome. However, the role of HBV-specific cellular immunity in viral containment in immune suppressed patients in general and in OLT recipients in particular is unclear. To test whether or not OLT recipients maintain robust HBV-specific cellular immunity, the cellular immune response against HBV was assessed in 15 OLT recipients and 27 individuals with chronic and 24 subjects with self-limited HBV infection, respectively; using an overlapping peptide set spanning the viral nucleocapsid- and envelope-protein sequences. The data demonstrate that OLT recipients mounted fewer but stronger clusters of differentiation (CD)8 T cell responses than subjects with self-limited HBV infection and showed a preferential targeting of the nucleocapsid antigen. This focused response pattern was similar to responses seen in chronically infected subjects with undetectable viremia, but significantly different from patients who presented with elevated HBV viremia and who mounted mainly immune responses against the envelope protein. In conclusion, virus-specific CD4 T cell–mediated responses were only detected in subjects with self-limited HBV infection. Thus, the profile of the cellular immunity against HBV was in immune suppressed patients similar to subjects with chronic HBV infection with suppressed HBV-DNA. Liver Transpl 2008. © 2008 AASLD.

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