Gastroenterology
Volume 129, Issue 6 , Pages 1937-1943 , December 2005

Steatosis Is a Cofactor in Liver Injury in Hemochromatosis

  • Elizabeth E. Powell

      Affiliations

    • School of Medicine, The University of Queensland, Brisbane, Australia
    • Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
    • Corresponding Author InformationAddress requests for reprints to: Elizabeth Powell, MD, PhD, Princess Alexandra Hospital, Ipswich Rd, Brisbane, Queensland, 4102 Australia.fax (61) 7 3240 2337.
    • ,
  • Azmat Ali

      Affiliations

    • Nutrition and Dietetic Services, Princess Alexandra Hospital, Brisbane, Australia
    • ,
  • Andrew D. Clouston

      Affiliations

    • School of Medicine, The University of Queensland, Brisbane, Australia
    • ,
  • Jeannette L. Dixon

      Affiliations

    • Population Studies & Human Genetics Division, Queensland Institute of Medical Research, Brisbane, Australia
    • ,
  • Douglas J. Lincoln

      Affiliations

    • Population Studies & Human Genetics Division, Queensland Institute of Medical Research, Brisbane, Australia
    • ,
  • David M. Purdie

      Affiliations

    • Northern California Cancer Center, Fremont, California
    • ,
  • Linda M. Fletcher

      Affiliations

    • School of Medicine, The University of Queensland, Brisbane, Australia
    • Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
    • ,
  • Lawrie W. Powell

      Affiliations

    • School of Medicine, The University of Queensland, Brisbane, Australia
    • Population Studies & Human Genetics Division, Queensland Institute of Medical Research, Brisbane, Australia
    • Royal Brisbane and Women’s Hospital, Brisbane, Australia
    • ,
  • Julie R. Jonsson

      Affiliations

    • School of Medicine, The University of Queensland, Brisbane, Australia

Received 11 May 2005 ,Accepted 31 August 2005.

References 

  1. Chopra M , Galbraith S , Darnton-Hill I . A global response to a global problem (the epidemic of overnutrition) . Bull World Health Organ . 2002;80:952–958
  2. Wanless IR , Lentz JS . Fatty liver hepatitis (steatohepatitis) and obesity (an autopsy study with analysis of risk factors) . Hepatology . 1990;12:1106–1110
  3. Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis . Hepatology . 1999;29:1215–1219
  4. Adinolfi LE , Gambardella M , Andreana A , Tripodi MF , Utili R , Ruggiero G . Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity . Hepatology . 2001;33:1358–1364
  5. Westin J , Nordlinder H , Lagging M , Norkrans G , Wejstal R . Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients . J Hepatol . 2002;37:837–842
  6. Raynard B, Balian A, Fallik D, Capron F, Bedossa P, Chaput JC, et al. Risk factors of fibrosis in alcohol-induced liver disease . Hepatology . 2002;35:635–638
  7. Naveau S , Giraud V , Borotto E , Aubert A , Capron F , Chaput JC . Excess weight risk factor for alcoholic liver disease . Hepatology . 1997;25:108–111
  8. Iturriaga H , Bunout D , Hirsch S , Ugarte G . Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics . Am J Clin Nutr . 1988;47:235–238
  9. Bellentani S , Tiribelli C . The spectrum of liver disease in the general population (lesson from the Dionysos study) . J Hepatol . 2001;35:531–537
  10. Reeves HL , Burt AD , Wood S , Day CP . Hepatic stellate cell activation occurs in the absence of hepatitis in alcoholic liver disease and correlates with the severity of steatosis . J Hepatol . 1996;25:677–683
  11. Sorensen TI , Orholm M , Bentsen KD , Hoybye G , Eghoje K , Christoffersen P . Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis . Lancet . 1984;2:241–244
  12. Teli MR , Day CP , Burt AD , Bennett MK , James OF . Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver . Lancet . 1995;346:987–990
  13. Bacon BR , Powell LW , Adams PC , Kresina TF , Hoofnagle JH . Molecular medicine and hemochromatosis (at the crossroads) . Gastroenterology . 1999;116:193–207
  14. Bassett ML , Halliday JW , Powell LW . Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis . Hepatology . 1986;6:24–29
  15. Deugnier YM, Loreal O, Turlin B, Guyader D, Jouanolle H, Moirand R, et al  Liver pathology in genetic hemochromatosis (a review of 135 homozygous cases and their bioclinical correlations) . Gastroenterology . 1992;102:2050–2059
  16. Fletcher LM , Dixon JL , Purdie DM , Powell LW , Crawford DH . Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis . Gastroenterology . 2002;122:281–289
  17. Beutler E , Felitti VJ , Koziol JA , Ho NJ , Gelbart T . Penetrance of 845G→A (C282Y) HFE hereditary haemochromatosis mutation in the USA . Lancet . 2002;359:211–218
  18. Adams PC . Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis? . Am J Gastroenterol . 2001;96:567–569
  19. Jazwinska EC, Cullen LM, Busfield F, Pyper WR, Webb SI, Powell LW, et al  Haemochromatosis and HLA-H . Nat Genet . 1996;14:249–251
  20. Searle JW , Kerr JFR , Halliday JW , Powell LW . Iron storage disease . In:  MacSween RNM ,  Anthony PP ,  Scheuer PJ editor. Pathology of the liver . 2nd ed.. Edinburgh, Scotland: Churchill Livingstone; 1987;p. 257–272
  21. Scheuer PJ . Classification of chronic viral hepatitis (a need for reassessment) . J Hepatol . 1991;13:372–374
  22. Powell EE , Cooksley WG , Hanson R , Searle J , Halliday JW , Powell LW . The natural history of nonalcoholic steatohepatitis (a follow-up study of forty-two patients for up to 21 years) . Hepatology . 1990;11:74–80
  23. Caldwell SH , Crespo DM . The spectrum expanded (cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease) . J Hepatol . 2004;40:578–584
  24. Wyatt J , Baker H , Prasad P , Gong YY , Millson C . Steatosis and fibrosis in patients with chronic hepatitis C . J Clin Pathol . 2004;57:402–406
  25. Bellentani S , Bedogni G , Miglioli L , Tiribelli C . The epidemiology of fatty liver . Eur J Gastroenterol Hepatol . 2004;16:1087–1093
  26. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al  Prevalence of hepatic steatosis in an urban population in the United States (impact of ethnicity) . Hepatology . 2004;40:1387–1395
  27. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, et al  Hemochromatosis and iron-overload screening in a racially diverse population . N Engl J Med . 2005;352:1769–1778
  28. Powell LW, Dixon JL, Ramm GA, Anderson GJ, Subramaniam VN, Purdie DM, et al  The penetrance of HFE-associated hemochromatosis as assessed by clinical evaluation and liver biopsy in subjects identified by health checks, family screening or population screening . Hepatology . 2004;40:574A
  29. Pietrangelo A . Iron, oxidative stress and liver fibrogenesis . J Hepatol . 1998;28(Suppl 1):8–13
  30. Burkitt MJ , Mason RP . Direct evidence for in vivo hydroxyl-radical generation in experimental iron overload (an ESR spin-trapping investigation) . Proc Natl Acad Sci U S A . 1991;88:8440–8444
  31. Kadiiska MB , Burkitt MJ , Xiang QH , Mason RP . Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation . J Clin Invest . 1995;96:1653–1657
  32. Houglum K , Filip M , Witztum JL , Chojkier M . Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload . J Clin Invest . 1990;86:1991–1998
  33. Pietrangelo A, Borella F, Casalgrandi G, Montosi G, Ceccarelli D, Gallesi D, et al  Antioxidant activity of silybin in vivo during long-term iron overload in rats . Gastroenterology . 1995;109:1941–1949
  34. Houglum K , Ramm GA , Crawford DH , Witztum JL , Powell LW , Chojkier M . Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis . Hepatology . 1997;26:605–610
  35. Pietrangelo A , Gualdi R , Casalgrandi G , Montosi G , Ventura E . Molecular and cellular aspects of iron-induced hepatic cirrhosis in rodents . J Clin Invest . 1995;95:1824–1831
  36. Diehl AM . Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines . Am J Physiol Gastrointest Liver Physiol . 2002;282:G1–G5
  37. Letteron P , Fromenty B , Terris B , Degott C , Pessayre D . Acute and chronic hepatic steatosis lead to in vivo lipid peroxidation in mice . J Hepatol . 1996;24:200–208

 Supported by the National Health and Medical Research Council of Australia (to E.E.P., A.D.C., J.L.D., L.W.P., and J.R.J.) and the Lions Medical Research Foundation, Australia (to J.R.J.).

PII: S0016-5085(05)01799-3

doi: 10.1053/j.gastro.2005.09.015

Gastroenterology
Volume 129, Issue 6 , Pages 1937-1943 , December 2005

Article Tools

* Image Usage & Resolution