Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B

Authors

  • Dr Yosuke Morimitsu,

    1. Biological Carcinogenesis Program, National Cancer Institute, Bethesda, MD
    Current affiliation:
    1. First Department of Pathology, Kurume University School of Medicine, Kurume, Japan
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  • David E. Kleiner Jr.,

    1. Laboratory of Pathology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute, Bethesda, MD
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  • Hari S. Conjeevaram,

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • Chu Chieh Hsia,

    1. Biological Carcinogenesis Program, National Cancer Institute, Bethesda, MD
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  • Dr Adrian M. Di Bisceglie,

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD
    Current affiliation:
    1. Department of Internal Medicine, St Louis University Health Science Center, St Louis, MO
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  • Edward Tabor MD

    Corresponding author
    1. Biological Carcinogenesis Program, National Cancer Institute, Bethesda, MD
    • National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
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Abstract

The effect of interferon alfa (IFN-α) therapy on the expression of transforming growth factor alpha (TGF-α) in the liver during chronic hepatitis B was investigated. Serial liver biopsy specimens were evaluated from 35 patients who had participated in a randomized, controlled trial of recombinant human IFN-α for the treatment of chronic hepatitis B. Percutaneous liver biopsy specimens obtained before and 1 year after entry in the trial were sectioned and stained with a monoclonal antibody to TGF-α in an avidin-biotin-peroxidase-complex system. The expression of TGF-α in each section was evaluated blindly (with respect to treatment group and order of biopsies) and was numerically scored. There was no significant difference in TGF-α expression before or after therapy between 13 patients receiving daily IFN-α, 13 receiving alternate-day IFN-α, and 9 receiving no therapy. Sustained clearance of HBV-DNA and DNA polymerase activity occurred in 8 of 26 treated patients (“responders”); the 18 other patients were “nonresponders.” Expression of TGF-α before IFN-α therapy was significantly higher in responders than in nonresponders; after IFN-α therapy, TGF-α expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-α in the liver, which was correlated with the severity of inflammation in the liver in this study, appeared to be predictive of the response to IFN-α therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond. (HEPATOLOGY 1995; 22:1021–1026.).

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