title: Understanding the hypercarcinogenic state in chronic hepatitis: a clue to the prevention of human hepatocellular carcinoma.
abstract: Human hepatocellular carcinomas (HCCs) are preceded by chronic hepatitis and cirrhosis. Despite a clear viral etiology (hepatitis B virus [HBV] and hepatitis C virus [HCV] of human hepatocarcinogenesis, the mechanism is complex and the distinct molecular pathway or molecules that explain this phenomenon are not yet known. Viral hepatitis, "inflammation-mediated" hepatocarcinogenesis, greatly influences the incidence of somatic genetic events in hepatocytes, by increasing the number of target cells or the proliferation of once-hit hepatocytes, eventually leading to HCC. We propose that hepatitis virus can cause HCC by a combination of two mechanisms; (i) cell killing and stimulation of mitosis, leading to an accumulation of events necessary for transformation; and (ii) an increase in chromosomal instability mediated by induced recombinogeneic protein(s) during chronic hepatitis. These conditions may be designated as the "hypercarcinogenic state". Our goal is to change the "hypercarcinogenic state" to the "normo- or hypocarcinogenic" state and to prevent HCC development.
authors.affiliation: Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 170-8455, Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kajino
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Umeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Arakawa
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D006518:Hepatitis Viruses / Q000235:genetics / Q000502:physiology*; D006521:Hepatitis, Chronic / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D011230:Precancerous Conditions / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*