Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with virus-induced chronic liver disease and response to interferon.

BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B, 15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage. METHODS: Oncoproteins were detected by indirect immunofluorescence using high affinity and monoclonal antibodies. Grade and stage of liver damage were measured by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%) hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier (p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no case was c-myc detected. Oncoproteins were correlated with the histological activity index (p < 0.0001) and its components: lobular degeneration and periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p < 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9 out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%) relapsed and none was a sustained responder. Conversely 9 out of 17 (53%) oncoprotein-negative patients, including 3 patients with histologically active cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos and c-myb were detected in chronic viral hepatitis patients, but not in non-viral liver diseases. Their expression correlated with the grade and stage of liver disease and with poor response to alpha-IFN.