{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:59:53Z","timestamp":1761487193179,"version":"3.30.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":6817,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,1]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>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\u2013nine 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\u2013END\/10 and Factor VIII. In addition, the liver homogenates and sera of HCV\u2013 or HBV\u2013positive 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\u2013positive patients compared with HBV\u2013infected subjects or controls (74% vs. 39% vs. 8%) (\u03c72 = 20.78;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; .0001) (HCV+ vs. HBV+ vs. controls). The degree of microvessel density was also higher in HCV\u2013 than in HBV\u2013positive patients or controls (\u03c72 = 12.28;<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; .005). In addition, HCV\u2013positive sera and liver homogenates stimulated a higher migration and proliferation of human endothelial cells<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>compared with HBV\u2013positive or control sera and liver homogenates. These observations indicate that angiogenesis is particularly linked to HCV infection, suggesting a possible contribution to HCV\u2013related liver oncogenesis.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510250142","type":"journal-article","created":{"date-parts":[[2004,7,27]],"date-time":"2004-07-27T23:03:48Z","timestamp":1090969428000},"page":"229-234","update-policy":"http:\/\/dx.doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":62,"title":["Chronic Viral Hepatitis Induced by Hepatitis C But Not Hepatitis B Virus Infection Correlates With Increased Liver Angiogenesis"],"prefix":"10.1097","volume":"25","author":[{"given":"R.","family":"Mazzanti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Messerini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Monsacchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Buzzelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. L.","family":"Zignego","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Monti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Laffi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Morbidelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Fantappi\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bartoloni Saint F.","family":"Omer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Ziche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.510250142-BIB1|cit1","first-page":"215","article-title":"Hepatocellular carcinoma and cirrhosis: a review of their relative incidence in a 25 year period in the Florence area","volume":"31","author":"Omer","year":"1984","journal-title":"Hepatogastroenterology"},{"key":"10.1002\/hep.510250142-BIB2|cit2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1056\/NEJM199109053251002","article-title":"Hepatocellular carcinoma in Italian patients","volume":"325","author":"Colombo","year":"1991","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.510250142-BIB3|cit3","first-page":"764","article-title":"Hepatocellular carcinoma and viral cirrhosis","volume":"20","author":"Gentilini","year":"1994","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.510250142-BIB4|cit4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/1097-0142(19880801)62:3<611::AID-CNCR2820620328>3.0.CO;2-0","article-title":"Risk factors for hepatocellular carcinoma in Italy. Male sex, hepatitis B virus, non A non B infection, and alcohol","volume":"62","author":"Villa","year":"1988","journal-title":"Cancer"},{"key":"10.1002\/hep.510250142-BIB5|cit5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0168-8278(91)90841-X","article-title":"Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis","volume":"12","author":"Caporaso","year":"1991","journal-title":"J Hepatol"},{"key":"10.1002\/hep.510250142-BIB6|cit6","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/hep.1840210308","article-title":"Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients","volume":"21","author":"Takano","year":"1995","journal-title":"HEPATOLOGY"},{"key":"10.1002\/hep.510250142-BIB7|cit7","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/hep.1840150532","article-title":"Hepatocellular carcinoma: recent 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