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

• Published in: Hepatology (Baltimore, Md.) Vol. 22; no. 4 Pt 1; p. 1021
• Main Authors: Morimitsu, Y, Kleiner, Jr, D E, Conjeevaram, H S, Hsia, C C, Di Bisceglie, A M, Tabor, E
• Format: Journal Article
• Language: English
• Published: United States 01.10.1995
• Subjects: Adult; Alanine Transaminase - blood; Antiviral Agents - therapeutic use; Female; Hepatitis B - metabolism; Hepatitis B - pathology; Hepatitis B - therapy; Hepatitis B - virology; Hepatitis B Surface Antigens - analysis; Humans; Immunohistochemistry; Interferon Type I - therapeutic use; Liver - metabolism; Liver - pathology; Liver - virology; Male; Middle Aged; Recombinant Proteins; Transforming Growth Factor alpha - metabolism
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220402

The effect of interferon alfa (IFN-alpha) therapy on the expression of transforming growth factor alpha (TGF-alpha) 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-alpha 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-alpha in an avidin-biotin-peroxidase-complex system. The expression of TGF-alpha 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-alpha expression before or after therapy between 13 patients receiving daily IFN-alpha, 13 receiving alternate-day IFN-alpha, 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-alpha before IFN-alpha therapy was significantly higher in responders than in nonresponders; after IFN-alpha therapy, TGF-alpha expression decreased significantly among responders compared with nonresponders and untreated controls. Thus, the level of expression of TGF-alpha 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-alpha therapy in chronic hepatitis B, with a higher level of expression indicating a greater likelihood that the patient would respond.