Expression of transforming growth factor alpha in the liver before and after interferon alfa therapy for chronic hepatitis B.
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.
Morimitsu
Y
Y
Biological Carcinogenesis Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kleiner
D E
DE
Conjeevaram
H S
HS
Hsia
C C
CC
Di Bisceglie
A M
AM
Tabor
E
E
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006509:Hepatitis B / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D000410:Alanine Transaminase