Advertisement

Hepatitis B Virus Infection and Hepatocellular Carcinoma

  • Harvey M. Lieberman
  • Ran Tur-Kaspa
  • David A. Shafritz

Abstract

The association between persistent infection with hepatitis B virus (HBV) and the development of hepatocellular carcinoma (HCC) has been strengthened by substantial recent evidence. This evidence consists of both retrospective and prospective epidemiological studies, molecular studies of human tissue and HCC cell lines obtained from human HBV carriers who developed liver cancer, and studies of animal models infected with viruses closely related to HBV. Although the mechanism(s) by which persistent HBV infection and development of HCC are related remain largely unknown, techniques of modern molecular biology offer the means by which such answers may be obtained in the future. In this chapter, evidence supporting the association between persistent infection with HBV and the development of primary liver cancer will be examined in the hope of offering insight into the possible mechanism(s) of carcinogenesis as related to HBV infection.

Keywords

Integrate Viral Sequence Integrate Hepatitis Hepadna Virus 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Smuzness W (1978) Hepatocellular carcinoma and hepatitis B virus: evidence for a casual association. Prog Med Virol 24:40–69Google Scholar
  2. 2.
    Blumberg BS, London WT (1981) Primary hepatocellular carcinoma and hepatitis B virus. In Hickey RC (ed) Current problems in cancer. Year Book Medical Publ, Chicago VI(I), pp 2–23Google Scholar
  3. 3.
    Beasley RP, Hwang L-Y (1984) Epidemiology of hepatocellular carcinoma. In Vyas GH, Dienstag JL, Hoofnagle JH (eds) Viral hepatitis and liver disease. Grune and Stratton, New York, pp 209–224Google Scholar
  4. 4.
    Tiollais P, Charnay P, Vyas GN (1981) Biology of hepatitis B virus. Science 213:406–411PubMedCrossRefGoogle Scholar
  5. 5.
    Summers J (1981) Three recently described animal virus models for human hepatitis B virus. Hepatology 1:179–183PubMedCrossRefGoogle Scholar
  6. 6.
    Summers J, Smolec JM, Snyder R (1978) A virus similar to hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci USA 75:4533–4537PubMedCrossRefGoogle Scholar
  7. 7.
    Marion PL, Oshiro LS, Regnery DC Scullard, GH, Robinson, WS (1980) A virus of Beechey ground squirrels that is related to hepatitis B virus of humans. Proc Natl Acad Sci USA 77:2941–2945PubMedCrossRefGoogle Scholar
  8. 8.
    Mason WS, Seal G, Summers J (1980) Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol 36:829–836PubMedGoogle Scholar
  9. 9.
    Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P (1979) Nucleotide sequence of the hepatitis B genome cloned in E. coli. Nature 281:646–650PubMedCrossRefGoogle Scholar
  10. 10.
    Mandart E, Kay A, Galibert F (1984) Nucleotide sequence of a cloned duck hepatitis virus genome: Comparison with the human and woodchuck hepatitis B virus sequences. J Virol 49: 782–792PubMedGoogle Scholar
  11. 11.
    Meyers ML, Trepo LV, Nath N, Sninsky JJ (1986) Hepatitis B virus polypeptide X: Expression in E. coli and identification of specific antibodies in sera from hepatitis B virus infected humans. J. Virol 57:101–109PubMedGoogle Scholar
  12. 12.
    Rall LB, Standring DN, Laub O, Rutter WJ (1983) Transcription of hepatitis B virus by RNA polymerase II. Mol Cell Biol 3:1766–1773PubMedGoogle Scholar
  13. 13.
    Shaul Y, Rutter WJ, Laub O (1985) A human hepatitis B viral enhancer element. EMBO J 4:427–430PubMedGoogle Scholar
  14. 14.
    Pourcell C, Louise A, Gervais M, Chenciner N, Dubois MF, Tiollais P (1982) Transcription of the hepatitis B surface antigen gene in mouse cells transformed with cloned viral DNA. J Virol 42:100–105Google Scholar
  15. 15.
    Chakraborty PR, Ruiz-Opazo N, Shafritz DA (1981) Transcription of human hepatitis B virus core antigen sequences in an in vitro HeLa cellular extract. Virology 111:647–652PubMedCrossRefGoogle Scholar
  16. 16.
    Laimonis AL, Khoury G, Gorman C, Howard B, Gruss P (1982) Host-specific activation of transcription by tandem repeats from simian virus 40 and Moloney murine sarcoma virus. Proc Natl Acad Sci USA 79:6453–6457CrossRefGoogle Scholar
  17. 17.
    Chisari FV, Pinkert CA, Milich DR, Filippi P, McLachlan A, Palmiter RD, Brinster RL (1985) A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. Science 230:1157–1160PubMedCrossRefGoogle Scholar
  18. 18.
    Jameel S, Siddiqui A (1986) The human hepatitis B virus enhancer requires trans-acting cellular factor(s) for activity. Mol Cell Biol 6:710–715PubMedGoogle Scholar
  19. 19.
    Tur-Kaspa R, Burk RD, Shaul Y, Shafritz DA (1986) Hepatitis B virus DNA contains a glucocorticoid responsive element. Proc Natl Acad Sci 83:1627–1631PubMedCrossRefGoogle Scholar
  20. 20.
    Geisse S, Scheidereit C, Westphal HM, Hynes NE, Groner B, Beato M (1982) Glucocorticoid receptors recognize DNA sequences in and around murine mammary tumor virus DNA. EMBO J 1:1613–1619PubMedGoogle Scholar
  21. 21.
    Summers J, Mason WS (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29:403–415PubMedCrossRefGoogle Scholar
  22. 22.
    Miller RH, Tran C-T, Robinson WS (1984) Hepatitis B virus particles in plasma and liver contain viral DNA-RNA hybrid molecules. Virology 139:53–63PubMedCrossRefGoogle Scholar
  23. 23.
    Shafritz DA, Kew MC (1981) Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas. Hepatology 1:1–8PubMedCrossRefGoogle Scholar
  24. 24.
    Shafritz DA Shouval D, Sherman HI, Hadziyannis SJ, Kew MC (1981) Integration of hepatitis B virus DNA into the genome of liver cells in chronic liver disease and hepatocellular carcinoma. N Engl J Med 305:1067–1073PubMedCrossRefGoogle Scholar
  25. 25.
    Lieberman HM, LaBrecque DR, Kew MC, Hadziyannis SJ, Shafritz DA (1983) Detection of hepatitis B virus directly in human serum by a simplified molecular hybridization test. Comparison to HBeAg/anti-HBe status in HBsAg carriers. Hepatology 3:286–291Google Scholar
  26. 26.
    Edman JC, Gray P, Valenzuela P, Rall LB, Rutter WJ (1980) Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature 286:535–538PubMedCrossRefGoogle Scholar
  27. 27.
    Brechot C, Pourcel C, Louise A, Rain B, Tiollais P (1980) Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma. Nature 286:533–535PubMedCrossRefGoogle Scholar
  28. 28.
    Koshy R, Maupas P, Muller R, Hofschneider PH (1981) Detection of hepatitis B virus-specific DNA in the genomes of human hepatocellular carcinoma and liver cirrhosis tissues. J Gen Virol 57:95–102PubMedCrossRefGoogle Scholar
  29. 29.
    Brechot C, Hadchouel M, Scotto J, Fonck M, Potet F, Vyas GN, Tiollais P (1981) State of hepatitis B virus DNA in hepatocytes of patients with hepatitis B surface antigen-positive and negative liver disease. Proc Natl Acad Sci USA 78:3906–3910PubMedCrossRefGoogle Scholar
  30. 30.
    Brechot C, Poucel C, Hadchouel M, Dejean A, Louise A, Scotto J, Tiollais P (1982) State of hepatitis B virus DNA in liver diseases. Hepatology 2:27S–34SGoogle Scholar
  31. 31.
    Bonino F, Hoyer B, Nelson J, Engle R, Verme G, Gerin J (1981) Hepatitis B virus DNA in the sera of HBs antigen carriers: a marker of active hepatitis B virus replication in the liver. Hepatology 1:386–391PubMedCrossRefGoogle Scholar
  32. 32.
    Brechot C, Scotto J, Hadchouel M, Charnay P, Degos F, Trepo C, Tiollais P (1981) Detection of hepatitis B virus DNA in liver and serum: a direct appraisal of the chronic carrier state. Lancet 2:765–767PubMedCrossRefGoogle Scholar
  33. 33.
    Berninger M, Hammer M, Hoyer B, Gerin J (1982) An assay for the detection of the DNA genome of hepatitis B virus in serum. J Med Virol 9: 57–68PubMedCrossRefGoogle Scholar
  34. 34.
    Scotto J, Hadchouel M, Hery C, Yvart J, Tiollais P, Brechot C (1983) Detection of hepatitis B virus DNA in serum by a simple spot hybridization technique: comparison with results for other viral markers. Hepatology 3:279–284PubMedCrossRefGoogle Scholar
  35. 35.
    Kam W, Rall LB, Smuckler EA, Schmid R, Rutter WJ (1982) Hepatitis B virus DNA in liver and serum of asymptomatic carriers. Proc Natl Acad Sci USA 79:7522–7526PubMedCrossRefGoogle Scholar
  36. 36.
    Weiler IVD, Fowler MJF, Monjardino J, Thomas HC (1982) The detection of HBV DNA in serum by molecular hybridization: a more sensitive method for detection of complete HBV particles. J Med Virol 9:273–280CrossRefGoogle Scholar
  37. 37.
    Sherlock S, Thomas HC (1983) Hepatitis B virus infection: the impact of molecular biology. Hepatology 3:455–456PubMedCrossRefGoogle Scholar
  38. 38.
    Hadziyannis SJ, Lieberman HM, Karvountzis GG, Shafritz DA (1983) Analysis of liver disease, nuclear HBcAg, viral replication and hepatitis B virus DNA in liver and serum of HBeAg vs. anti-HBe positive carriers of hepatitis B virus. Hepatology 3:656–662PubMedCrossRefGoogle Scholar
  39. 39.
    Fattovich G, Rugge M, Brollo L, Portisso P, Noventa F, Guido M, Alberti A, Realdi G (1986) Clinical, virological and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B. Hepatology 6:167–172PubMedCrossRefGoogle Scholar
  40. 40.
    Yokosuka O, Omata M, Imazeki F, Okuda K (1985) Active and inactive replication of hepatitis B virus DNA in chronic liver disease. Gastroenterology 89:610–616PubMedGoogle Scholar
  41. 41.
    Shafritz DA (1982) Hepatitis B virus DNA molecules in the liver of HBsAg carriers: mechanistic considerations in the pathogenesis of hepatocellular carcinoma. Hepatology 2:35S–41SGoogle Scholar
  42. 42.
    Tooze J (1980) DNA tumor viruses. Part 2 of molecular biology of tumor viruses. Cold Spring Harbor Laboratory, New YorkGoogle Scholar
  43. 43.
    Macnab GM, Alexander JJ, Lacatsas G, Bey EM, Urbanowitz JM (1976) Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer 34:504–515CrossRefGoogle Scholar
  44. 44.
    Bassendine MF, Arborgh BAM, Shipton U, Monjardino J, Aranguibel F, Thomas HC, Sherlock S (1980) Hepatitis B surface antigen and alphafetoprotein secreting human primary liver cell cancer in athymic mice. Gastroenterology 79: 528–532PubMedGoogle Scholar
  45. 45.
    Desmyter J, Ray MB, Bradburne AF, Alexander JJ (1978) Human HBsAg-positive hepatoma in nude athymic mice. In: Vyas GN, Cohen SN, Schmid R (eds) Viral hepatitis. Proceedings of the Second Symposium on Viral Hepatitis. Franklin Institute, Philadelphia, pp 459–460Google Scholar
  46. 46.
    Marion PL, Salazar FH, Alexander JJ, Robinson WS (1980) State of hepatitis B viral DNA in a human hepatoma cell line. J Virol 33:795–806PubMedGoogle Scholar
  47. 47.
    Dejean A, Brechot C, Tiollais P, Wain-Hobson S (1983) Characterization of integrated hepatitis B viral DNA cloned from a human hepatoma and the hepatoma derived cell line PLC/PRF/5. Proc Natl Acad Sci USA 80:2505–2509PubMedCrossRefGoogle Scholar
  48. 48.
    Koshy R, Koch S, Freytag von Loringhoven A, Kahmann R, Murray K, Hofschneider PH (1983) Integration of hepatitis B virus DNA: evidence for integration in the single-stranded gap. Cell 34:215–223PubMedCrossRefGoogle Scholar
  49. 49.
    Ziemer M, Garcia P, Shaul Y, Rutter WJ (1985) Sequence of hepatitis B virus DNA incorporated into the genome of a human hepatoma cell line. J Virol 53:885–892PubMedGoogle Scholar
  50. 50.
    Koch S, Freytag von Loringhoven A, Hofschneider PH, Koshy R (1984) Amplification and rearrangement in hepatoma cell DNA associated with integrated hepatitis B virus DNA. EMBO J 3:2185–2189PubMedGoogle Scholar
  51. 51.
    Koch S, Freytag von Loringhoven A, Kahmann R, Hofschneider PH, Koshy R (1984) The genetic organization of integrated hepatitis B virus DNA in the human hepatoma cell line PLC/ PRF/5. Nucleic Acid Res 12:6871–6886PubMedCrossRefGoogle Scholar
  52. 52.
    Ou J-H, Rutter WJ (1985) Hybrid hepatitis B virus-host transcripts in a human hepatoma cell. Proc Natl Acad Sci USA 82:83–87PubMedCrossRefGoogle Scholar
  53. 53.
    Twist EM, Clark HF, Aden DP, Knowles BB, Plotkin SA (1981) Integration pattern of hepatitis B virus DNA sequences in human hepatoma cell lines. J Virol 37:239–243PubMedGoogle Scholar
  54. 54.
    He L, Shih C, Isselbacher KJ, Goodman HM, Wands JR (1983) Integration of HBV into genome of a new hepatocellular carcinoma cell line (CUSPF). Gastroenterology 84:1184Google Scholar
  55. 55.
    Das PK, Nayak N, Tsiquaye KN, Zuckerman AJ (1980) Establishment of a human hepatocellular cell line releasing hepatitis B virus surface antigen. Br J Exp Pathol 61:648–654PubMedGoogle Scholar
  56. 56.
    Koike K, Koyabashi M, Mizusawa H, Yoshida E, Yaginuma K, Taira M (1983) Rearrangement of the surface antigen gene of hepatitis B virus integrated in the human hepatoma cell lines. Nucl Acid Res 11:5391–5403CrossRefGoogle Scholar
  57. 57.
    Mizusawa H, Taira M, Yaginuma K, Kobayashi M, Yoshida E, Koike K (1985) Inversely repeating integrated hepatitis B virus DNA and cellular flanking sequences in the human hepatomaderived cell line huSP. Proc Natl Acad Sci USA 82:208–212PubMedCrossRefGoogle Scholar
  58. 58.
    Geissler E, Theile M (1983) Virus-induced gene mutations of eukaryotic cells. Human Genet 63:1–12CrossRefGoogle Scholar
  59. 59.
    Mounts P, Kelly TJ, Jr. (1984) Rearrangements of host and viral DNA in mouse cells transformed by simian virus 40. J Mol Biol 177:431–460PubMedCrossRefGoogle Scholar
  60. 60.
    Matsuo T, Heller M, Petti L, O’Shiro E, Kieff E (1984) Persistence of the entire Epstein-Barr virus genome integrated into human lymphocyte DNA. Science 226:1322–1324PubMedCrossRefGoogle Scholar
  61. 61.
    Dejean A, Sonigo P, Wain-Hobson S, Tiollais P (1984) Specific hepatitis B virus integration in hepatocellular carcinoma DNA through a viral 11-base-pair direct repeat. Proc Natl Acad Sci USA 81: 5350–5354PubMedCrossRefGoogle Scholar
  62. 62.
    Rogler CE, Sherman M, Su CY, Shafritz DA (1985) Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science 230:319–322PubMedCrossRefGoogle Scholar
  63. 63.
    Brechot C, Nalpas B, Courouce AM, Duhamel G, Callard P, Carnot F, Tiollais P, Berthelot P (1982) Evidence that hepatitis B virus has a role in liver cell carcinoma in alcoholic liver disease. New Engl J Med 306:1384–1387PubMedCrossRefGoogle Scholar
  64. 64.
    Shafritz DA, Lieberman HM, Isselbacher KJ, Wands JR (1982) Monoclonal radioimmunoassays for hepatitis B surface antigen. Demonstration of hepatitis B virus DNA or related sequences in serum and viral epitopes in immune conplexes. Proc Natl Acad Sci USA 79: 5675–5679PubMedCrossRefGoogle Scholar
  65. 65.
    Wands JR, Lieberman HM, Muchmore E, Isselbacher K, Shafritz DA (1982) Detection and transmission in chimpanzees of hepatitis B virusrelated agents formerly designated “non-A, nunB” hepatitis. Proc Natl Acad Sci USA 79:7552–7556PubMedCrossRefGoogle Scholar
  66. 66.
    Figus A, Blum HE, Vyas GH, De Virgilis S, Cao A, Lippi M, Lai E, Balestrieri A (1984) Hepatitis B viral nucleotide sequences in non-A, non-B or hepatitis B virus-related chronic liver disease. Hepatology 4:364–368PubMedCrossRefGoogle Scholar
  67. 67.
    Brechot C, Degos F, Lugassy C, Thiers V, Zafrani S, Franco D, Bismuth H, Trepo C, Benhamou J-P, Wands J, Isselbacher K, Tiollais P, Berthelot P (1985) Hepatitis B virus DNA in patients with chronic liver disease and negative tests for hepatitis B surface antigens. New Engl J Med 312:270–276PubMedCrossRefGoogle Scholar
  68. 68.
    Figus A, Fung Y-KT, Blum HE, Vyas GN, Varmus HE (1984) Definition of a deletion mutant of hepatitis B virus DNA that appears to replicate in the chronically infected liver of a Sardinian patient with B°-thalassemia. In: Vyas GN, Dienstag JL, Hoofnagle JH (eds) Viral hepatitis and liver disease. Grune and Stratton, New York, p 632Google Scholar
  69. 69.
    Popper H, Shih JW-K, Gerin JL, Wong DC, Hoyer BH, London WT, Sly DL, Purcell RH (1981) Woodchuck hepatitis virus and hepatocellular carcinoma: correlation of histological and virological observations. Hepatology 1:91–98PubMedCrossRefGoogle Scholar
  70. 70.
    Snyder RL, Summers J (1980) Woodchuck hepatitis virus and hepatocellular carcinoma. In: Essex M, Todaro G, ZurHausen M (eds) Viruses in naturally occurring cancers, vol.7. Proceedings of Cold Spring Harbor Symposium on Cell Proliferation 1979. Cold Spring Harbor Laboratory, New York, pp 446–457Google Scholar
  71. 71.
    Ogston CW, Jonak GJ, Rogler CE, Astrin SM, Summers J (1982) Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from hepatocellular carcinomas of woodchucks. Cell 29:385–394PubMedCrossRefGoogle Scholar
  72. 72.
    Rogler CE, Summers J (1984) Cloning and structural analysis of integrated woodchuck hepatitis virus sequences from a chronically infected liver. J Virol 50:832–837PubMedGoogle Scholar
  73. 73.
    Rogler CE, Summers J (1982) Novel forms of woodchuck hepatitis virus DNA isolated from chronically infected woodchuck liver nuclei. J Virol 44:852–863PubMedGoogle Scholar
  74. 74.
    Rogler CE, Summers J, Shafritz DA (1984) Molecular characteristics of woodchuck and human hepatitis virus in persistent infections of the liver and associated hepatic neoplasms. In: Gallo RC, Essex M, Gross L (eds) Human T-cell leukemia/ lymphoma viruses. Cold Spring Harbor Laboratory, New York, pp 55–67Google Scholar
  75. 75.
    Moriarty AM, Alexander H, Lerner RA, Thornton GB (1985) Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma. Science 227:429–433PubMedCrossRefGoogle Scholar
  76. 76.
    Varmus HE (1982) Form and function of retroviral proviruses. Science 216:812–820PubMedCrossRefGoogle Scholar
  77. 77.
    Temin HM, (1982) Function of the retrovirus large terminal repeat. Cell 28: 3–5PubMedCrossRefGoogle Scholar
  78. 78.
    Mason WS, Taylor JM, Hull R (1987) Retroid virus genome replication. In: Moramorosch K, Murphy FA, Shortkin AJ (eds) Advances in virus research. Academic Press, New York (in press)Google Scholar
  79. 79.
    Miller RH, Robinson WS (1986) Common evolutionary origin of hepatitis B virus and retroviruses. Proc Natl Acad Sci USA 83:2531–2535PubMedCrossRefGoogle Scholar
  80. 80.
    Bishop JM (4981) The enemy within: genesis of retrovirus oncogenes. Cell 23: 5–6CrossRefGoogle Scholar
  81. 81.
    Hunter T (1980) Proteins phosphorylated by the RSV transforming function. Cell 22:647–648PubMedCrossRefGoogle Scholar
  82. 82.
    Neel BG, Hayward WS, Robinson HL, Fang J, Astrin SM (1981) Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNA’s: oncogenesis by promoter insertion. Cell 23: 323–334PubMedCrossRefGoogle Scholar
  83. 83.
    Murray MJ, Shilo B-Z, Shih C, Cowing D, Hsu HW, Weinberg RA (1981) Three different human tumor cell lines contain different oncogenes. Cell 25: 355–361PubMedCrossRefGoogle Scholar
  84. 84.
    Gough NM, Murray K (1982) Expression of the hepatitis B virus surface, core and e antigen genes by stable rat and mouse cell lines. J Mol Biol 162:43–67PubMedCrossRefGoogle Scholar
  85. 85.
    Lieber CS, Seitz HK, Garro AJ, Worner TM (1979) Alcohol-related diseases and carcinogenesis. Cancer Res 39:2863–2886PubMedGoogle Scholar
  86. 86.
    Bulatao-Jayme J, Alermo E, Castro MC, Jardelezo MT, Salamat L (1982) A case-control dietary study of primary liver cancer risk from aflatoxin exposure. Int J Epidemiol 11:112–119PubMedCrossRefGoogle Scholar
  87. 87.
    Edmondson HA and Peters RL (1982) Neoplasms of the liver. In: Schiff L, Schiff ER (eds) Diseases of the liver, 5th edn. Lippincott, Philadelphia, pp 1101–1157Google Scholar
  88. 88.
    Shikata_T (1976) Primary liver carcinoma and liver cirrhosis. In: Okudo K, Peters RL (eds) Hepatocellular carcinoma. Wiley, New York, pp 53–71Google Scholar
  89. 89.
    Falk H (1982) Liver. In: Schrottenfeld D, Franmoni JF (eds) Cancer epidemiology and prevention. Saunders, Philadelphia, pp 668–682Google Scholar
  90. 90.
    Kew MC (1982) Tumors of the liver In: Zakim D, Boyer TD (eds) Hepatology. A textbook of liver diseases Saunders, Philadelphia, pp 1048–1084Google Scholar
  91. 91.
    Eriksson S, Carlson J, Velez R (1986) Risk of cirrhosis and primary liver cancer in alpha-l-antitrypsin deficiency. New Engl J Med 314: 736–739PubMedCrossRefGoogle Scholar
  92. 92.
    Shibreski K, Soga K, Homma A, Ichida F (1981) Hepatic cancer and non-A non-B type hepatitis. Nippon Rinsko 39:3251–3256Google Scholar
  93. 93.
    Obata H, Hayashi H, Matoike Y, Hisamitsu T, Okuda H, Kobayashi S, Nishioka K (1980) A prospective study on the development of hepatocullular carcinoma from liver cirrhosis with persistent hepatitis B infection. Int J Cancer 25:741–747PubMedCrossRefGoogle Scholar
  94. 94.
    Kew MC, Rossouw E, Hodkinson J, Paterson A, Dusheiko GM, Whitcutt JM (1983) Hepatitis B virus status of South African blacks with hepatocellular carcinoma: Comparison between rural and urban patients. Hepatology 3:65–68PubMedCrossRefGoogle Scholar
  95. 95.
    Su DL Drinking water and liver cell cancer: An epidemiological approach to the etiology of this disease in China. Chin Med J 92:748-756Google Scholar
  96. 96.
    Salaman MH, Rowson KEK, Roe JFC, Ball JK, Harvey JJ, De Benedictis G (1963) The combined action of viruses and other carcinogens. In: Viruses, nucleic acids and cancer. University of Texas MD Anderson Hospital and Tumor Institute, 17th Annual Symposium on Fundamental Cancer Research. Williams and Wilkins, Baltimore, pp 544–558Google Scholar
  97. 97.
    Rous P, Kidel JA (1938) The carcinogenic effect of a papilloma virus on the tarred skin of rabbits: I. Description of the phenomenon. J Exp Med 67:399–428PubMedCrossRefGoogle Scholar
  98. 98.
    Casto BC, DiPaulo JA (1973) Viruses, chemicals and cancer. Prog Med Virol 16:1–47PubMedGoogle Scholar
  99. 99.
    Lavi S (1981) Carcinogen mediated amplification of viral DNA sequences in simian virus 40 transformed Chinese hamster embryo cells. Proc Natl Acad Sci USA 78:6144–6148PubMedCrossRefGoogle Scholar
  100. 100.
    Tiollais P, Pourcel C, Dejean A (1985) the hepatitis B virus. Nature 317:488–496CrossRefGoogle Scholar
  101. 101.
    Shafritz_DA, Hadziyannis SJ (1984) Hepatitis B virus DNA in liver and serum, viral antigens and antibodies, virus replication and liver disease activity in patients with persistent hepatitis B virus infection. In: Chisari (ed) Advances in hepatitis research. Masson, New York, pp 80–90Google Scholar

Copyright information

© Springer Japan 1987

Authors and Affiliations

  • Harvey M. Lieberman
    • 1
  • Ran Tur-Kaspa
    • 1
  • David A. Shafritz
    • 2
  1. 1.Department of Medicine, Marion Bessin Liver Research CenterAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of Cell Biology, Marion Bessin Liver Research CenterAlbert Einstein College of MedicineBronxUSA

Personalised recommendations