Steatohepatitis/Metabolic Liver Disease

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HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis†

  1. James E. Nelson1,
  2. Renuka Bhattacharya1,
  3. Keith D. Lindor2,
  4. Naga Chalasani3,
  5. Stuart Raaka1,
  6. E. Jenny Heathcote4,
  7. Emil Miskovsky5,
  8. Eldon Shaffer6,
  9. Stephen J. Rulyak1,
  10. Kris V. Kowdley1,‡,*

Article first published online: 6 AUG 2007

DOI: 10.1002/hep.21742

Issue

Hepatology

Hepatology

Volume 46, Issue 3, pages 723–729, September 2007

Additional Information

How to Cite

Nelson, J. E., Bhattacharya, R., Lindor, K. D., Chalasani, N., Raaka, S., Heathcote, E. J., Miskovsky, E., Shaffer, E., Rulyak, S. J. and Kowdley, K. V. (2007), HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis. Hepatology, 46: 723–729. doi: 10.1002/hep.21742

Author Information

  1. 1

    University of Washington Medical Center, Seattle, WA

  2. 2

    Mayo Clinic College of Medicine, Bloomington, IN

  3. 3

    Indiana University, Bloomington, IN

  4. 4

    University of Toronto, Toronto, Ontario, Canada

  5. 5

    University of Texas Medical Branch, Galveston, TX

  6. 6

    University of Calgary, Calgary, Alberta, Canada

  1. ‡

    fax: 206-598-3884

*University of Washington Medical Center, 1959 NE Pacific Street, Box 356174, Seattle, WA 98195

  1. †

    Potential conflict of interest: Nothing to report.

  2. ‡

    fax: 206-598-3884

Publication History

  1. Issue published online: 24 AUG 2007
  2. Article first published online: 6 AUG 2007
  3. Manuscript Accepted: 27 MAR 2007
  4. Manuscript Received: 18 JAN 2007

Funded by

  • NIH. Grant Numbers: DK02957, DK38215
  • Axcan-Pharma
  • General Clinical Research Center. Grant Number: M01-RR-00037
  • Clinical Nutrition Research Unit at the University of Washington. Grant Number: P30 DK035816
  • NIH

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References

  • 1
    Hunter DJ, Halliday ML, Coates RA, Rankin JG. Hospital morbidity from cirrhosis of the liver and per capita consumption of absolute alcohol in Ontario, 1978 to 1982: a descriptive analysis. Can J Public Health 1988; 79: 243–248.
  • 2
    Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006; 40(3 Suppl 1 ): S5–S10.
  • 3
    McCullough AJ. Update on nonalcoholic fatty liver disease. J Clin Gastroenterol 2002; 34: 255–262.
  • 4
    Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. HEPATOLOGY 2006; 43(2 Suppl 1 ): S99–S112.
    Direct Link:
  • 5
    Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003; 98: 960–967.
    Direct Link:
  • 6
    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998; 114: 842–845.
  • 7
    Day CP. Pathogenesis of steatohepatitis. Best Pract Res Clin Gastroenterol 2002; 16: 663–678.
  • 8
    Whittington CA, Kowdley KV. Haemochromatosis. Aliment Pharmacol Ther 2002; 16: 1963–1975.
    Direct Link:
  • 9
    Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996; 13: 399–408.
  • 10
    Bonkovsky HL, Lambrecht RW, Shan Y. Iron as a co-morbid factor in nonhemochromatotic liver disease. Alcohol 2003; 30: 137–144.
  • 11
    Tung BY, Emond MJ, Bronner MP, Raaka SD, Cotler SJ, Kowdley KV. Hepatitis C, iron status, and disease severity: relationship with HFE mutations. Gastroenterology 2003; 124: 318–326.
  • 12
    Chitturi S, Weltman M, Farrell GC, McDonald D, Kench J, Liddle C, et al. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. HEPATOLOGY 2002; 36: 142–149.
    Direct Link:
  • 13
    Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 2448–2455.
    Direct Link:
  • 14
    Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 421–429.
  • 15
    George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114: 311–318.
  • 16
    Valenti L, Dongiovanni P, Fracanzani AL, Santorelli G, Fatta E, Bertelli C, et al. Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary hemochromatosis. Dig Liver Dis 2003; 35: 172–178.
  • 17
    Bugianesi E, Manzini P, D'Antico S, Vanni E, Longo F, Leone N, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. HEPATOLOGY 2004; 39: 179–187.
    Direct Link:
  • 18
    Loria P, Lonardo A, Carulli N. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. HEPATOLOGY 2004; 39: 1748.
    Direct Link:
  • 19
    Deguti MM, Sipahi AM, Gayotto LC, Palacios SA, Bittencourt PL, Goldberg AC, et al. Lack of evidence for the pathogenic role of iron and HFE gene mutations in Brazilian patients with nonalcoholic steatohepatitis. Braz J Med Biol Res 2003; 36: 739–745.
  • 20
    Zamin I Jr, Mattos AA, Mattos AZ, Mignon E, Bica C, Alexandre COP. Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis. Arq Gastroenterol 2006; 43: 224–228.
  • 21
    Yamauchi N, Itoh Y, Tanaka Y, Mizokami M, Minami M, Morita A, et al. Clinical characteristics and prevalence of GB virus C, SEN virus, and HFE gene mutation in Japanese patients with nonalcoholic steatohepatitis. J Gastroenterol 2004; 39: 654–660.
  • 22
    Duseja A, Das R, Nanda M, Das A, Garewal G, Chawla Y. Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations. World J Gastroenterol 2005; 11: 393–395.
  • 23
    Bacon BR. Hemochromatosis: diagnosis and management. Gastroenterology 2001; 120: 718–725.
  • 24
    Moirand R, Mendler MH, Guillygomarc'h A, Brissot P, Deugnier Y. Non-alcoholic steatohepatitis with iron: part of insulin resistance-associated hepatic iron overload? J Hepatol 2000; 33: 1024–1026.
  • 25
    Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467–2474.
    Direct Link:
  • 26
    George PM, Conaghan C, Angus HB, Walmsley TA, Chapman BA. Comparison of histological and biochemical hepatic iron indexes in the diagnosis of genetic haemochromatosis. J Clin Pathol 1996; 49: 159–163.
  • 27
    Emond MJ, Bronner MP, Carlson TH, Lin M, Labbe RF, Kowdley KV. Quantitative study of the variability of hepatic iron concentrations. Clin Chem 1999; 45: 340–346.
  • 28
    Olynyk JK, O'Neill R, Britton RS, Bacon BR. Determination of hepatic iron concentration in fresh and paraffin-embedded tissue: diagnostic implications. Gastroenterology 1994; 106: 674–677.
  • 29
    Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, et al; Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005 28; 352: 1769–1778.
  • 30
    Beutler E, Felitti V, Gelbart T, Ho N. The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Intern Med 2000; 133: 329–337.
  • 31
    Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KJ. Geography of HFE C282Y and H63D mutations. Genet Test 2000; 4: 183–198.
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