Type D hepatitis: The clinical significance of hepatitis D virus RNA in serum as detected by a hybridization-based assay

Authors

  • Antonina Smedile,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Mario Rizzetto,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Katherine Denniston,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Ferruccio Bonino,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Frances Wells,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Giorgio Verme,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Fausto Consolo,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Bill Hoyer,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Robert H. Purcell,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • John L. Gerin Ph.D.

    Corresponding author
    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20852
    2. Division of Gastroenterology, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy
    3. Clinica Medica I, University of Messina, Messina, Italy
    4. Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    • Division of Molecular Virology and Immunology, Georgetown University, 5640 Fishers Lane, Rockville, Maryland 20852
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Abstract

Hepatitis D virus is a defective human pathogen that requires hepatitis B virus for its replication. A hybridization-based assay for the 1.75 kb RNA genome of hepatitis D virus was developed using as probe a radiolabeled transcript of a cloned cDNA fragment (pKD3 hepatitis D virus DNA). Sera from 120 chronic carriers of HBsAg with confirmed hepatitis D virus infection were analyzed for the presence of hepatitis D virus RNA. Serum hepatitis D virus RNA was detected in 43 of 74 (58%) patients with chronic liver disease; some patients were positive for hepatitis D virus RNA in multiple samples over a period of several years. Serum hepatitis D virus RNA was present in 17 of 28 (61%) patients during the acute phase of clinical hepatitis and was not detected after recovery from acute disease or in 18 asymptomatic chronic HBsAg carriers with antibody to hepatitis D virus. The presence of hepatitis D virus RNA correlated with other known markers of active hepatitis D virus replication; all chronic active liver disease patients with serum hepatitis D virus RNA were positive for antihepatitis D antigen IgM, and 34 of 37 (92%) had hepatitis D antigen in their liver biopsy specimens.

The assay for hepatitis D virus RNA provides a direct and noninvasive method for the detection of hepatitis D virus in serum and will be useful in the study of the natural history of type D hepatitis, the identification of chronic hepatitis D virus carriers likely to transmit hepatitis D virus and the selection and monitoring of patients for potential antiviral therapy.

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