Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus infection correlates with increased liver angiogenesis.
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections lead to cirrhosis and increase the risk for the development of hepatocellular carcinoma (HCC). Angiogenesis is an essential step in oncogenesis and contributes to tumor progression in adult organs; however, to what extent angiogenesis occurs in the liver during chronic viral hepatitis has not been studied. Ninety-nine matched patients affected by chronic hepatitis due to either HBV or HCV were studied together with 13 controls (5 patients were affected by familial hyperbilirubinemia with normal liver histology; 6 patients with stage II primary biliary cirrhosis; and 2 patients with pseudo inflammatory tumor). Microvessel density was assessed in liver biopsies by immunostaining using two different antibodies against endothelial cell antigens, QB-END/10 and Factor VIII. In addition, the liver homogenates and sera of HCV- or HBV-positive patients and controls were tested for their capacity to stimulate the migration and proliferation of freshly isolated human endothelial cells in vitro. Evidence of angiogenesis was significantly more frequent in HCV-positive patients compared with HBV-infected subjects or controls (74% vs. 39% vs. 8%) (chi2 = 20.78; P < .0001) (HCV+ vs. HBV+ vs. controls). The degree of microvessel density was also higher in HCV- than in HBV-positive patients or controls (chi2 = 12.28; P < .005). In addition, HCV-positive sera and liver homogenates stimulated a higher migration and proliferation of human endothelial cells in vitro compared with HBV-positive or control sera and liver homogenates. These observations indicate that angiogenesis is particularly linked to HCV infection, suggesting a possible contribution to HCV-related liver oncogenesis.
Mazzanti
R
R
Institute of Internal Medicine, University of Florence, Italy.
Messerini
L
L
Monsacchi
L
L
Buzzelli
G
G
Zignego
A L
AL
Foschi
M
M
Monti
M
M
Laffi
G
G
Morbidelli
L
L
Fantappié
O
O
Bartoloni Saint Omer
F
F
Ziche
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008099:Liver / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*