Hepatitis B virus infection in patients with idiopathic liver disease

Authors

  • T. Jake Liang M.D.,

    Corresponding author
    1. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    2. Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129
    3. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
    • Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, 149 13th St., 7th Floor, Charlestown, MA 02129
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  • Yaacov Baruch,

    1. Department of Medicine B, Rambam Medical Center, Faculty of Medicinc, Technion, 31096 Haifa, Israel
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  • Edna Ben-Porath,

    1. Virology Laboratory, Rambam Medical Center, Faculty of Medicinc, Technion, 31096 Haifa, Israel
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  • Rafael Enat,

    1. Department of Medicine B, Rambam Medical Center, Faculty of Medicinc, Technion, 31096 Haifa, Israel
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  • Lucyna Bassan,

    1. Pathology Department, Rambam Medical Center, Faculty of Medicinc, Technion, 31096 Haifa, Israel
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  • Nancy V. Brown,

    1. Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129
    2. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
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  • Nurit Rimon,

    1. Virology Laboratory, Rambam Medical Center, Faculty of Medicinc, Technion, 31096 Haifa, Israel
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  • Hubert E. Blum,

    1. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    2. Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129
    3. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
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  • Jack R. Wands

    1. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    2. Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129
    3. Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
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Abstract

We studied 67 HBsAg-negative Israeli patients (36 negative for all HBV serological markers as group 1 and 31 positive for antibodies to HBs and HBc as group 2) with chronic liver disease and cirrhosis of unknown origin using a rapid, sensitive and specific assay for the detection of low levels of hepatitis B virus in serum. This technique uses a high-affinity monoclonal antibody to HBs against an a domain epitope of HBsAg to capture the virion, followed by hepatitis B virus DNA amplification with the polymerase chain reaction. In addition, 55 subjects without liver disease served as controls: Group 3 (n = 32) was negative for all hepatitis B virus markers; group 4 (n = 23) was positive for antibodies to HBs and HBc. We found 11 individuals in group 1 (31%) and 10 in group 2 (29%) harboring low levels of hepatitis B virus DNA in serum. In contrast, no one in group 3 or group 4 was positive by this technique (p < 0.0001). Using polymerase chain reaction primers spanning other regions of the hepatitis B virus genome and a method of restriction-fragment analysis of polymerase chain reaction–amplified sequences, we detected significant DNA sequence heterogeneity, suggesting infection with distinct hepatitis B virus strains. DNA extracted from paraffin-embedded liver biopsy specimens of 42 patients from groups 1 and 2 was shown to contain hepatitis B virus DNA by polymerase chain reaction in 11 of 12 patients with circulating virion DNA. More important, 18 additional patients whose sera were negative by HBs-antibody capture/polymerase chain reaction amplification had hepatitis B virus DNA sequences in their livers. Hepatitis C virus antibodies were found in 71% of group 1, in 65% of group 2, in 3% of group 3 and in 4% of group 4 (p < 0.0001). Coexistence of hepatitis B virus infection and hepatitis C virus antibodies were common (>30%). We conclude that infection with hepatitis B virus undetectable by conventional assays and with hepatitis C virus may represent important unrecognized causes of idiopathic chronic liver disease in Israel, accounting for the possible origin in more than 90% of patients. (HEPATOLOGY 1991;13:1044–1051.)

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