Hepatitis C virus infection and hepatocellular carcinoma

  • Toshio Shikata


For the past two decades, hepatitis B virus (HBV) has been believed to be one of causative factors in hepatocellular carcinoma (HCC) in humans, especially in areas where HBV is endemic [1-3]. There is some evidence to support the close relationship between chronic HBV infection and development of HCC; for instance, areas where there is a high prevalence of HCC correspond to endemic areas of HBV. In Asia and Africa, both the HBV carrier rate and HCC incidence are very high. On the contrary, in areas where HBV infection is uncommon, such as the United States, the incidence of HCC is also low. Furthermore, the percentage of patients testing positive for HBsAg (hepatitis B surface antigen) is high among patients with HCC in those endemic areas, for example, 80% in Taiwan [4] and 72% in Uganda [5]. In addition, HBV DNA has been proved to be integrated into cellular DNA of tumor cells in patients with HBsAg-positive HCC [6-9] and non-tumor hepatocytes [10].


Liver Cancer Study Group Woodchuck Hepatitis Virus Develop Liver Cirrhosis Infected Chimpanzee HBsAg Negative Case 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Szmuness W (1978) Hepatocellular carcinoma and the hepatitis B virus: Evidence for a causal association. Prog Med Virol 24: 40–69PubMedGoogle Scholar
  2. 2.
    Shikata T (1976) Primary liver carcinoma and liver cirrhosis. In: Okuda K, Peters RL (eds) Hepatocellular Carcinoma. Wiley, New York, pp 53–71Google Scholar
  3. 3.
    Blumberg BS, Larouze B, London WT, Werner B, Hesser JE, Millman I, Saimot G, Payet M (1975) The relation of infection with the hepatitis B agent to primary hepatic carcinoma. Am J Pathol 81: 669–682PubMedGoogle Scholar
  4. 4.
    Tong MJ, Sun SC, Scheffer BT, Chang N, Lo K, Peters RL (1971) Hepatitis-associated antigen and hepatocellular carcinoma in Taiwan. Ann Intern Med 75: 687–691PubMedGoogle Scholar
  5. 5.
    Tabor E, Gerty RJ, Vogel CL, Bayley AC, Anthony PP, Chen CH, Barker LF (1977) Hepatitis B virus infection and primary hepatocellular carcinoma. J Nat Cancer Inst 58: 1197–1200PubMedGoogle Scholar
  6. 6.
    Shafritz D, Kew MC (1981) Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinoma. Hepatology 1: 1–8PubMedCrossRefGoogle Scholar
  7. 7.
    Brechot C, Pourcel C, Hadchouel M, Scotto J, Fonk M, Potet F, Vyas GN, Tiollais P (1982) State hepatitis B virus DNA in liver disease. Hepatology 2 (Suppl): 27–34Google Scholar
  8. 8.
    Hino O, Kitagawa T, Koike K, Kobayashi M, Hara M, Mori W, Nakashima T, Hattori N, Sugano H (1984) Detection of hepatitis B virus DNA in hepatocellular carcinoma in Japan. Hepatology 4: 90–95PubMedCrossRefGoogle Scholar
  9. 9.
    Miller RH, Lee SC, Liaw YF, Robinson WS (1985) Hepatitis B viral DNA in infected human liver and hepatocellular carcinoma. J Inf Dis 151: 1081–1092CrossRefGoogle Scholar
  10. 10.
    Tanaka Y, Esumi M, Shikata T (1988) Frequent integration of hepatitis B virus DNA in noncancerous liver tissue from hepatocellular carcinoma patients. J Med Virol 26: 7–14PubMedCrossRefGoogle Scholar
  11. 11.
    Summers J, Smolec JM, Snyder R (1978) A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci USA 75: 4533–4537PubMedCrossRefGoogle Scholar
  12. 12.
    Abe K, Kurata T, Shikata T (1988) Localization of woodchuck hepatitis virus in the liver. Hepatology 8: 88–92PubMedCrossRefGoogle Scholar
  13. 13.
    Mason WS, Seal G, Summers J (1980) Virus of Peking ducks with structural and biological relatedness to human hepatitis B virus. J Virol 36: 829–836PubMedGoogle Scholar
  14. 14.
    Okuda K, The Liver Cancer Study Group of Japan (1980) Primary liver cancer in Japan. Cancer 45: 2663–2669Google Scholar
  15. 15.
    The Liver Cancer Study Group of Japan (1984) Primary liver cancer in Japan. Cancer 54: 1747–1755CrossRefGoogle Scholar
  16. 16.
    The Liver Cancer Study Group of Japan (1987) Primary liver cancer in Japan. Cancer 60: 1400–1411CrossRefGoogle Scholar
  17. 17.
    Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244: 359–362PubMedCrossRefGoogle Scholar
  18. 18.
    Abe K, Kurata T, Shikata T (1989) Non-A, non-B hepatitis: Visualization of virus-like particles from chimpanzee and human sera. Arch Virol 104: 351PubMedCrossRefGoogle Scholar
  19. 19.
    Maeno M, Kaminaka K, Sugimoto H, Esumi M, Hayashi N, Komatu K, Abe K, Sekiguchi S, Yano M, Mizuno K, Shikata T (1990) A clone closely associated with non-A, non-B hepatitis. Nucleic Acids Res 18: 2685–2689PubMedCrossRefGoogle Scholar
  20. 20.
    Okamoto H, Okada S, Sugiyama S, Yotsumoto S, Tanaka T, Yoshizawa H, Tsuda F, Miyakawa Y, Mayumi M (1990) The 5’-terminal sequence of the hepatitis C virus genome. Jap J Exp Med 60: 167–177PubMedGoogle Scholar
  21. 21.
    Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, Shimotono K (1990) Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci USA 87: 9524–9528PubMedCrossRefGoogle Scholar
  22. 22.
    Takamizawa A, Mori C, Fuke S, Manabe S, Murakami S, Fujita J, Onishi E, Andho T, Yoshida I, Okayama H (1991) Structure and organization of the hepatitis C virus genome isolated from human carriers. J Virol 65: 1105–1113PubMedGoogle Scholar
  23. 23.
    Kubo Y, Takeuchi K, Boonmar S, Katayama T, Choo QL, Kuo G, Weiner DW, Bradley DW, Houghton M, Saito I, Miyamura T (1989) A cDNA fragment of hepatitis C virus isolated from an implicated donor of post-transfusion non-A, non-B hepatitis in Japan. Nucleic Acids Res 17: 10367–10372PubMedCrossRefGoogle Scholar
  24. 24.
    Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter MJ, Stevens CE, Tegtmeier GE, Bonono F, Colombo M, Lee WS, Kuo C, Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244: 362–364PubMedCrossRefGoogle Scholar
  25. 25.
    Nishioka K, Watanabe J, Furuta S, Tanaka E, Suzuki H, lino S, Tsuji T, Yano M, Kuo G, Choo QL, Houghton M, Oda T (1991) Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan. Liver 11: 65–70PubMedGoogle Scholar
  26. 26.
    Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, Furuta S, Akahane Y, Nishioka K, Purcell RH, Alter HJ (1990) Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: Analysis by detection of antibody to hepatitis C virus. Hepatology 12: 671–675PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1992

Authors and Affiliations

  • Toshio Shikata
    • 1
  1. 1.Department of PathologyNihon University School of MedicineItabashi-ku, TokyoJapan

Personalised recommendations