Hepatocellular Carcinoma in Hemochromatosis

  • Robin A. Bradbear
  • June W. Halliday
  • Mark L. Bassett
  • W. Graham Cooksley
  • Lawrie W. Powell


The term “hemochromatosis” has been used in the past to refer to disorders in which excessive iron intake (enterai or parenteral) or absorption leads to an increase in body iron stores, with deposition of iron primarily in the parenchymal cells of the liver, heart, and other organs leading eventually to organ failure. Genetic hemochromatosis is an inherited disease in which an inappropriately high iron absorption from the small intestine is associated with a progressive increase in body iron stores. Hemochromatosis is now widely used to refer to this inherited disease, and the term “secondary iron overload” is used to refer to iron overload resulting from hematological defects or blood transfusions.


Iron Overload Hereditary Hemochromatosis Body Iron Store Hepatic Iron Concentration Idiopathic Hemochromatosis 
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  1. 1.
    Sheldon JH (1935) Haemochromatosis. Oxford University Press, LondonGoogle Scholar
  2. 2.
    Powell LW, Bassett ML, Halliday JW (1980) Haemochromatosis—1980 Update. Gastroenterology 78:374–81PubMedGoogle Scholar
  3. 3.
    Grace ND, Powell LW (1974) Iron storage disorders of the liver. Gastroenterology 64:1257–83Google Scholar
  4. 4.
    Milder MS, Cook JD, Stray S, Finch CA (1980) Idiopathic hemochromatosis, an interim report. Medicine 59:34–49PubMedCrossRefGoogle Scholar
  5. 5.
    Jacobs A (1980) The pathology of iron overload. In: Jacobs A, Worwood M (eds) Iron in biochemistry and medicine: II. Academic Press, London, pp 428–61Google Scholar
  6. 6.
    Stocks AE, Powell LW (1973) Carbohydrate intolerance in idiopathic haemochromatosis and cirrhosis of the liver. Quart J Med 42:733–49PubMedGoogle Scholar
  7. 7.
    Walsh CH, Malins JM, Bloom SR (1978) Diabetes mellitus in idiopathic haemochromatosis. Br Med J 2:1267–8PubMedCrossRefGoogle Scholar
  8. 8.
    Bassett ML, Halliday JW, Powell LW (1986) Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 6:24–29PubMedCrossRefGoogle Scholar
  9. 9.
    Bacon BR, Tavill AS, Brittenham GM, et al (1983) Hepatic lipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest 71:429–39PubMedCrossRefGoogle Scholar
  10. 10.
    Park CH, Stassen WN, Bacon BR, Brittenham GM, Louis L, Tavill AS (1985) Hepatic fibrosis in rats with chronic dietary iron overload. Hepatology 5:950 (abstr)Google Scholar
  11. 11.
    Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G (1985) Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 313:1256–62PubMedCrossRefGoogle Scholar
  12. 12.
    Simon M, Pawlotsky Y, Bourel M, Fauchet R, Genetet B (1975) Hemochromatose idiopathique: maladie associée a l’antigene tissulaire HL-A3? La Nouvelle Presse Médicale 4:1432PubMedGoogle Scholar
  13. 13.
    Simon M, Bourel M, Fauchet R, Genetet B (1976) Association of HLA-A3 and HLA-B14 antigens with idiopathic hemochromatosis. Gut 17:332–334PubMedCrossRefGoogle Scholar
  14. 14.
    Cartwright GE, Edwards CQ, Kravitz K, Skolnick M, Amos DB, Johnson A, Buskjaer L (1979) Hereditary hemochromatosis: phenotypic expression of the disease. N Engl J Med 301:175–9PubMedCrossRefGoogle Scholar
  15. 15.
    Bassett ML, Doran TJ, Halliday JW, Bashir HV, Powell LW (1982) Idiopathic hemochromatosis: demonstration of homozygous-heterozygous mating by HLA typing of families. Hum Genet 60:352–6PubMedCrossRefGoogle Scholar
  16. 16.
    Simon M, Bourel M, Genetet B, Fauchet R (1977) Idiopathic hemochromatosis: demonstration of recessive transmission and early detection by family HLA typing. N Engl J Med 297:1017–21PubMedCrossRefGoogle Scholar
  17. 17.
    Bassett ML, Halliday JW, Powell LW (1984) Genetic Hemochromatosis. In: Seminars in liver disease Berk PD (ed) Thieme-Stratton, New YorkGoogle Scholar
  18. 18.
    Doran TJ, Bashir HV, Trejaut J, Bassett ML, Halliday JW, Powell LW (1981) Idiopathic haemochromatosis in the Australian population: HLA linkage and recessivity. Hum Immunol 2:191–200PubMedCrossRefGoogle Scholar
  19. 19.
    Bassett ML, Halliday JW, Ferris RA, Powell LW (1984) Diagnosis of hemochromatosis in young subjects: predictive accuracy of biochemical screening tests. Gastroenterology 87:628–33PubMedGoogle Scholar
  20. 20.
    Muir WA, McLaren GD, Braun W, Askari A (1984) Evidence for heterogeneity in hereditary hemochromatosis: evaluation of 174 persons in nine families. Am J Med 76:806–14PubMedCrossRefGoogle Scholar
  21. 21.
    Mallory FB (1932) Cirrhosis of the liver. N Engl J Med 206:1231–9CrossRefGoogle Scholar
  22. 22.
    MacDonald RA (1957) Primary carcinoma of the liver: a clinicopathological study of one hundred and eight cases. Arch Int Med 99:266–79CrossRefGoogle Scholar
  23. 23.
    Berk JE, Lieber, MM (1941) Primary carcinoma of liver in hemochromatosis. Am J Med Sci 202:708–714CrossRefGoogle Scholar
  24. 24.
    Stewart MJ (1922) Carcinoma of the liver in cirrhosis and hemochromatosis Br Med J 2:1066CrossRefGoogle Scholar
  25. 25.
    Finch SC, Finch CA (1955) Idiopathic hemochromatosis, an iron storage disease: A. Iron metabolism in hemochromatosis. Medicine (Baltimore) 34: 381–430CrossRefGoogle Scholar
  26. 26.
    Bomford A, Williams R (1976) Long term results of venesection therapy in idiopathic haemochromatosis. Quart J Med 45:611–23PubMedGoogle Scholar
  27. 27.
    Bradbear RA, Bain C, Siskind V, Schofield FD, Webb S, Axelsen EM, Halliday JW, Bassett ML, Powell LW (1985) Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver disease. J Nat Cancer Inst 75:81–4PubMedGoogle Scholar
  28. 28.
    Purtillo DT, Gottlieb LS (1973) Cirrhosis and hepatoma occurring at Boston City Hospital (1917–1968). Cancer 32:458–62CrossRefGoogle Scholar
  29. 29.
    MacSween RNM (1974) A clinicopathological review of 100 cases of primary malignant tumors of the liver. J Clin Pathol 27:669–82PubMedCrossRefGoogle Scholar
  30. 30.
    Powell LW (1970) Changing concepts of haemochromatosis. Postgrad Med J 46:200–209PubMedCrossRefGoogle Scholar
  31. 31.
    Melia WM, Wilkinson ML, Portmann BC, Johnson PJ, Williams R (1984) Hepatocellular carcinoma in the non-cirrhotic liver: a comparison with that complicating cirrhosis. Quart J Med 53:391–400PubMedGoogle Scholar
  32. 32.
    Powell LW, Mortimer R, Harris OD (1971) Cirrhosis of the liver: A comparative study of the four major aetiological groups. Med J Australia 1: 941–50PubMedGoogle Scholar
  33. 33.
    South Australian Central Cancer Registry unit (1983) Cancer in South Australia—Incidence, mortality and survival, 1977–81—Incidence and mortality 1981. South Australian Health Commission, AdelaideGoogle Scholar
  34. 34.
    Australian Bureau of Statistics (1983) Estimated resident population by sex and age: States and Territories of Australia, June 1977 to June 1982. Australian Government Publishing Service, CanberraGoogle Scholar
  35. 35.
    Ford JR (1981) Australian life tables 1975–1977. Office of the Australian Government Actuary, CanberraGoogle Scholar
  36. 36.
    Bailar JC (III) (1964) Significance factors for the ratio of a Poisson variable to its expectation. Biometrics 20:639–43CrossRefGoogle Scholar
  37. 37.
    Ammann RW, Muller E, Bansky J, Schuler G, Hacki WH (1980) High incidence of extrahepatic carcinomas in idiopathic hemochromatosis. Scand J Gastroenterol 15:733–6PubMedCrossRefGoogle Scholar
  38. 38.
    Bassendine MF, Chadwick RG, Lyssiotis T, Thomas HC, Sherlock S, Cohen BJ (1979) Primary liver cell cancer in Britain—a viral aetiology? Br Med J 1:166PubMedCrossRefGoogle Scholar
  39. 39.
    Okuda H, Obata H, Saito A, Tomimatsu M, Hisamitsu T, Takasaki T, Kobayashi S (1986) Hepatocellular carcinoma not associated with cirrhosis. A clinicopathological study in 41 patients including 29 resected cases. J Gastroent Hepatol 1:129–137CrossRefGoogle Scholar
  40. 40.
    Richmond HG (1959) Induction of sarcoma in the rat by iron-dextran complex. Br Med J 1:947–9PubMedCrossRefGoogle Scholar
  41. 41.
    Greenberg G (1976) Sarcoma after intramuscular iron injection. Brit Med J 1:1508–9PubMedCrossRefGoogle Scholar
  42. 42.
    Weinbren K, Salm R, Greenberg G (1978) Intramuscular injections of iron compounds and oncogenesis in man. Br Med J 1:683–5PubMedCrossRefGoogle Scholar
  43. 43.
    Weinberg ED (1981) Iron and neoplasia. Biol Trace Elem Res 3:55–80CrossRefGoogle Scholar
  44. 44.
    Nettesheim P, Creasia DA, Mitchell TJ (1975) Carcinogenic and cocarcinogenic effects of inhaled synthetic smog and ferric oxide particles. J Natl Cancer Inst 55:159–69PubMedGoogle Scholar
  45. 45.
    Antoine D, Braun P, Cervoni P, Schwartz P, Lamy P (1979) Le cancer bronchique des mineurs de fer de Lorraine—peut-il etre considere comme une maladie professionelle? A propos de 270 nouveaux cas observes de 1964 a 1978. Rev Fr Mal Respir 7:63–5Google Scholar
  46. 46.
    Weinberg ED (1984) Iron withholding: a defense against infection and neoplasia. Physiol Rev 64:65–102PubMedGoogle Scholar
  47. 47.
    Seiden C, Owen M, Hopkins JMP, Peters TJ (1980) Studies on the concentration and intracel-lular localization of iron proteins in liver biopsy specimens from patients with iron; overload with special reference to their role in lysosomal disruption. Br J Haematol 44:593–603CrossRefGoogle Scholar
  48. 48.
    Seiden C, Seymour CA, Peters TJ (1980) Activities of some free-radical scavenging enzymes and glutathione concentrations in human and rat liver and their relationship to the pathogenesis of tissue damage in iron overload. Clin Sci 58:211–9Google Scholar
  49. 49.
    Bergeron RJ, Streiff RR, Elliott GT (1985) Influence of iron in vivo proliferation and lethality of L1210 cells. JNutr 115:369–74Google Scholar
  50. 50.
    Van Asbeck BS, Verbrugh HA, Van Oost BA, Marx JJM, Imhoff HW, Verhoef J (1982) Listeria monocytogenes meningitis and decreased phagocytosis associated with iron overload. Br Med J 284: 542–4CrossRefGoogle Scholar
  51. 51.
    De Sousa M, Nishiya K (1978) Inhibition of E-rosette formation by two iron salts. Cell Immunol 38:203–8PubMedCrossRefGoogle Scholar
  52. 52.
    Matzner Y, Hershko C, Polliack A, Konijn AM, Izak G (1979) Suppressive effect of ferritin on in vitro lymphocyte function. Br J Haematol 42: 345–53PubMedCrossRefGoogle Scholar
  53. 53.
    Bryan CF, Nishiya K, Pollack MS, Dupont B, De Sousa M (1981) Differential inhibition of the MLR by iron: association with HLA phenotype. Immunogenetics 12:129–40PubMedCrossRefGoogle Scholar
  54. 54.
    Nishiya K, De Sousa M, Tsoi E, Bognacki JJ, De Harven E (1980) Regulation of expression of a human lymphoid cell surface marker by iron. Cell Immunol 53:71–83PubMedCrossRefGoogle Scholar
  55. 55.
    Keown P, Descamps-Latscha B (1983) In vitro suppression of cell-mediated immunity by ferroproteins and ferric salts. Cell Immunol 80:257–66PubMedCrossRefGoogle Scholar
  56. 56.
    Good MF, Halliday JW, Powell LW (1985) A method for analysing the clonal precursors of concanavalin A-induced suppressor cells. J Immunol Meth 80:163–175CrossRefGoogle Scholar
  57. 57.
    Good MF, Halliday JW, Powell LW (1984) Natural killer cell function and clonal analysis of immune responses in hemochromatosis and experimental iron overload. Hepatology 4(5): 1021 (abstract)Google Scholar
  58. 58.
    Good MF, Chapman D, Rudd M, Halliday JW, Powell LW (1985) The immunoregulatory effect of non-transferrin-bound iron and iron-overload. Hepatology 5(5): 983 (abstr)Google Scholar
  59. 59.
    Milman N, Laursen J, Podenphant J, Asnaes S (1986) Trace elements in normal and cirrhotic human liver tissue: I. Iron, copper zinc, selenium, manganese, titanium and lead measured by X-ray fluorescence spectrometry. Liver (in press) 197Google Scholar
  60. 60.
    Lustbader ED, Hann H-WL, Blumberg BS (1983) Serum ferritin as a predictor of host response to hepatitis B virus infection. Science 220:423–5PubMedCrossRefGoogle Scholar
  61. 61.
    Brechot C, Pasquinelli C, Saadi P, Deugnier Y, Simon M, Brissot P, Bourel M (1985) Liver hepatitis B virus DNA sequences in the liver of patients with hepatocellular carcinoma and primary haemochromatosis. Hepatology 5:970 (abstr)Google Scholar
  62. 62.
    Powell LW (1975) The role of alcoholism in hepatic iron storage disease. Am NY Acad Sci 252:124–134CrossRefGoogle Scholar
  63. 63.
    Saddi RS, Ebelin P, Pouliquen A, Gautreau C, Durand J, Jammet P, Courouce AM, Brechot C Franco D, Thibult N (1985) Hepatitis B vaccination and idiopathic haemochromatosis. Lancet 2:1061–1062PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 1987

Authors and Affiliations

  • Robin A. Bradbear
  • June W. Halliday
  • Mark L. Bassett
  • W. Graham Cooksley
  • Lawrie W. Powell
    • 1
  1. 1.The Liver Unit, Departments of Medicine and BiochemistryUniversity of QueenslandBrisbaneAustralia

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