Transforming growth factor alpha (TGF-alpha) is expressed at high levels in human hepatocellular carcinoma (HCC); it may be part of a mechanism by which hepatitis B virus (HBV) causes HCC. Research has continued in the analysis of the role of TGF-alpha in the etiology of HCC. Previous work in this laboratory has shown high levels of TGF-alpha expression in most human HCCs, and an up-regulation of the TGF-alpha gene in a hepatoblastoma cell line after transfection with the hepatitis B virus (HBV). Although a few studies have been published on TGF-alpha in HCC, none have examined TGF-alpha expression in liver over the course of time, or the effect of interferon alpha (IFN-alpha) therapy for the treatment of chronic hepatitis B on the expression of TGF-alpha in the liver. Serial liver biopsies 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 biopsies obtained before and one 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 """"""""non-responders."""""""" 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 to nonresponders and untreated controls.
