Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with virus-induced chronic liver disease and response to interferon.
OBJECTIVE
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.
Tappero
G
G
Department of Internal Medicine, University of Turin, S. Luigi Hospital, Orbassano, Italy.
Farina
M
M
Negro
F
F
Anfossi
G
G
Mattiello
L
L
Giuli
P D
PD
Colombatto
P
P
Brunetto
M R
MR
Angeli
A
A
Bonino
F
F
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D016762:Genes, fos; D016259:Genes, myc; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006521:Hepatitis, Chronic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000235:genetics*
D000998:Antiviral Agents; D016898:Interferon-alpha; D020626:Oncogene Proteins v-myb; D015682:Retroviridae Proteins, Oncogenic