Pathology of hepatic iron overload

Seminars in Liver Disease

Volumn 25, Issue 4, 2005, Pages 392-401

  Brunt, Elizabeth M ^a,b  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Saint Louis University   (United States)

Author keywords

Hereditary hemochromatosis; HFE; Parenchymal iron overload; Reticuloendothelial iron

Indexed keywords

HFE PROTEIN; IRON;

CANCER RISK; CHRONIC LIVER DISEASE; DIAGNOSTIC IMAGING; DIFFERENTIAL DIAGNOSIS; DISEASE CLASSIFICATION; GENE MUTATION; HEMOCHROMATOSIS; HIGH RISK PATIENT; HISTOPATHOLOGY; HOMOZYGOTE; HUMAN; IRON METABOLISM; IRON OVERLOAD; IRON STORAGE; LABORATORY TEST; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER FIBROSIS; LIVER LEVEL; PRACTICE GUIDELINE; PRIORITY JOURNAL; QUANTITATIVE ANALYSIS; REVIEW; TECHNIQUE; TISSUE DISTRIBUTION;

BIOPSY; DIAGNOSIS, DIFFERENTIAL; HUMANS; IRON; IRON OVERLOAD; LIVER;

EID: 28444454836     PISSN: 02728087     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2005-923311     Document Type: Review

References (84)

1. Feder JN, Gnirke A, Thomas W, et al.. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 1996;13:399-408
2. Pietrangelo A. Non-invasive assessment of hepatic iron overload: are we finally there? J Hepatol 2005;42:153-154
3. Bacon BR, Powell LW, Adams PC, Kresina TF, Hoofnagle JH. Molecular medicine and hemochromatosis: at the cross-roads. Gastroenterology 1999;116:193-207
4. Bacon BR. Hereditary hemochromatosis: diagnosis and management. Gastroenterology 2001;120:718-725
5. Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK. HFE genotype in patients with hemochromatosis and other liver diseases. Ann Intern Med 1999;130:953-962
6. Bridle KR, Crawford DHG, Fletcher LM, Smith JL, Powell LW, Ramm GA. Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis. J Hepatol 2003;38:426-433
7. Hubscher SG. Iron overload, inflammation and fibrosis in genetic haemochromatosis [editorial]. J Hepatol 2003;38:521-525
8. Ramm GA, Crawford DHG, Powell LW, Walker NI, Fletcher LM, Halliday JW. Hepatic stellate cell activation in genetic haemochromatosis. Lobular distribution, effect of increasing hepatic iron and response to phlebotomy. J Hepatol 1997;26:584-592
9. Ludwig J, Batts KP, Moyer PM, Baldus WP, Fairbanks VF. Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm. Mayo Clin Proc 1993;68:263-267
10. Brunt EM, Olynyk JK, Britton RS, Janney CG, Di Bisceglie AM, Bacon BR. Histological evaluation of iron in liver biopsies: relationship to HFE mutations. Am J Gastroenterol 2000;95:1788-1793
11. Turlin B, Deugnier Y. Evaluation and interpretation of iron in the liver. Semin Diagn Pathol 1998;15:237-245
12. Bartolo C, McAndrew PE, Sosolik RC, et al.. Differential diagnosis of hereditary hemochromatosis from other liver disorders by genetic analysis. Arch Pathol Lab Med 1998;122:633-637
13. Tavill AS. Diagnosis and management of hemochromatosis. Hepatology 2001;33:1321-1328
14. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996;110: 1107-1119
15. Olynyk JK, St. Pierre TG, Britton RS, Brunt EM, Bacon BR. Duration of hepatic iron exposure increases the risk of significant fibrosis in hereditary hemochromatosis: a new role for magnetic resonance imaging. Am J Gastroenterol 2005;100:837-841
16. Fargion S, Mattioli M, Fracanzani AL, Fiorelli G. Iron and liver diseases. Can J Gastroenterol 2000;14:89D-92D
17. Pietrangelo A. Hemochromatosis gene modifies courses of hepatitis C viral infection. Gastroenterology 2003;124:1509-1523
18. Fletcher LM, Dixon JL, Purdie DM, Powell LW, Crawford DHG. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology 2002;122:281-289
19. Tavill AS, Qadri AM. Alcohol and iron. Semin Liver Dis 2004;24:317-325
20. Chitturi S, George J. Interaction of iron, insulin resistance, and nonalcoholic steatohepatitis. Curr Gastroenterol Rep 2003;5:18-25
21. Bugianesi E, Manzini P, D'Antico S, et al.. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004;39:179-187
22. Eriksson S, Lindmark B, Olsson S. Lack of association between hemochromatosis and alpha-antitrypsin deficiency. Acta Med Scand 1986;219:291-294
23. Fargion S, Bissoli F, Fracanzani AL, et al.. No association between genetic hemochromatosis and α1-antitrypsin deficiency. Hepatology 1996;24:1161-1164
24. Elzouki A-NY, Hultcrantz R, Stal P, Befrits R, Eriksson S. Increased PiZ gene frequency for α1-antitrypsin in patients with genetic haemochromatosis. Gut 1995;36:922-926
25. Rabinovitz M, Gavaler JS, Kelly RH, Van Thiel DH. Association between heterozygous α1-antitrypsin deficiency and genetic hemochromatosis. Hepatology 1992;16:145-148
26. Scheuer PJ, Williams R, Muir AR. Hepatic pathology in relatives of patients with haemochromatosis. J Pathol Bacteriol 1962;84:53-64
27. Deugnier YM, Loreal O, Turlin B, et al.. Liver pathology in genetic hemochromatosis: a review of 135 homozygous cases and their bioclinical correlations. Gastroenterology 1992;102:2050-2059
28. Diwakaran HH, Befeler AS, Britton RS, Brunt EM, Bacon BR. Accelerated hepatic fibrosis in patients with combined hereditary hemochromatosis and chronic hepatitis C infection. J Hepatol 2002;36:687-691
29. Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999;341:718-724
30. Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology 2002;122:646-651
31. Schoniger-Hekele M, Muller C, Polli C, Wrba F, Penner E, Ferenci P. Liver pathology in compound heterozygous patients for hemochromatosis mutations. Liver 2002;22:295-301
32. Pietrangelo A. Non-HFE hemochromatosis. Hepatology 2004;39:21-29
33. Pietrangelo A, Caleffi A, Henrion J, et al.. Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology 2005;128:470-479
34. Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med 2005;352:1741-1744
35. Eason RJ, Adams PC, Aston CE, Searle J. Familial iron overload with possible autosomal dominant inheritance. Aust N Z J Med 1990;20:226-230
36. Morita H, Ikeda S, Yamamoto K, et al. Hereditary ceruloplasminemia deficiency with hemochromatosis: a clinicopathological study of a Japanese family. Ann Neurol 1995;37:646-656
37. Fairbanks VT, Beutler E. Congenital atransferrinemia and idiopathic pulmonary hemosiderosis. In: Williams WJ, Beutler E, Erslev AJ, eds. Hematology. New York, NY: McGraw Hill; 1983:489-492
38. Kershisnik MM, Knisely AS, Sun C-CJ, Andrews JM, Wittwer CT. Cytomegalovirus infection, fetal liver disease, and neonatal hemochromatosis. Hum Pathol 1992;23:1075-1080
39. Adams PC, Agnew S. Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. Hepatology 1996;3:724-727
40. Jakobovits AW, Morgan MY. Hepatic siderosis in alcoholics. Dig Dis Sci 1979;24:305-310
41. 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
42. Brunt EM. Alcoholic and nonalcoholic steatohepatitis. Clin Liver Dis 2002;6:399-420
43. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis 2001;21:3-16
44. 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
45. Brunt EM, Neuschwander-Tetri BA, Oliver D, Wehmeier KR, Bacon BR. Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol 2004;35:1070-1085
46. Ferrannini E. Insulin resistance, iron, and the liver. Lancet 2000;355:2181-2182
47. George DK, Goldwurm S, MacDonald GA, et al.. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998;114:311-318
48. Bonkovsky HL, Zivny J, Tortorelli K, Liu Q, Lambrecht RW. Non-alcoholic steatohepatitis with iron: part of insulin resistance-associated hepatic iron overload? Reply. J Hepatol 2000;33:1025-1026
49. Facchini FS, Hua NW, Stoohs RA. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 2002;122:931-939
50. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30:1356-1362
51. Chitturi S, Weltman M, Farrell GC, 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
52. Bhattacharya R, Kowdley KV. Iron and HFE mutations in nonalcoholic steatohepatitis: innocent bystanders or accessories to the crime? Gastroenterology 2003;125:615-616
53. Yamauchi N, Itoh Y, Tanaka Y, 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
54. Mendler MH, Turlin B, Moirand R, et al.. Insulin resistance-associated hepatic iron overload. Gastroenterology 1999;117: 1155-1163
55. Turlin B, Mendler M-H, Moirand R, Guyader D, Guillygomarc'h A, Deugnier Y. Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients. Am J Clin Path 2001;116:263-270
56. Bardadin KA, Scheuer PJ. Endothelial cell changes in acute hepatitis: a light and electron microscopic study. J Pathol 1984;144:213-220
57. Ishak KG. Light microscopic morphology of viral hepatitis. Am J Clin Pathol 1976;65:(5 Suppl):787-827
58. Hengeveld P, Zuyderhoudt FM, Jobsis AC, van Gool J. Some aspects of iron metabolism during acute viral hepatitis. Hepatogastroenterology 1982;29:138-141
59. Kaji K, Nakanuma Y, Sasaki M, Unoura M, Kobayashi K-I, Nonomura A. Hemosiderin deposition in portal endothelial cells: a novel hepatic hemosiderosis frequent in chronic viral hepatitis B and C. Hum Pathol 1995;26:1080-1085
60. Barton AL, Banner BF, Cable EE, Bonkovsky H. Distribution of iron in the liver predicts the response of chronic hepatitis C infection to interferon therapy. Am J Clin Pathol 1995;103:419-424
61. Pianko S, McHutchison JG, Gordon SC, et al.. Hepatic iron concentration does not influence response to therapy with interferon plus ribavirin in chronic HCV infection. J Interferon Cytokine Res 2002;22:483-489
62. Bonkovsky H, Banner BF, Rothman AL. Iron and chronic viral hepatitis. Hepatology 1997;25:759-768
63. Lefkowitch JH, Yee HT, Sweeting J, Green PHR, Magun AM. Iron-rich foci in chronic viral hepatitis. Hum Pathol 1998;29:116-118
64. Fiel MI, Schiano TD, Guido M, et al.. Increased hepatic iron deposition resulting from treatment of chronic hepatitis C with ribavirin. Am J Clin Path 2000;113:35-39
65. Scheuer PJ, Lefkowitch JH. Disturbances of copper and iron metabolism. In: Scheuer PJ, Lefkowitch JH, eds. Liver Biopsy Interpretation. London, UK: WB Saunders; 2000:275-283
66. Brunt EM, Tavill AS, Bacon BR. A 49-year-old man with a1-antitrypsin deficiency and abnormal iron study results. Semin Liver Dis 1996;16:97-101
67. Graziadei IW, Joseph JJ, Wiesner RH, Therneau TM, Batts KP, Porayko MK. Increased risk of chronic liver failure in adults with heterozygous a1-antitrypsin deficiency. Hepatology 1998;28:1058-1063
68. Ludwig J, Hashimoto E, Porayko MK, Moyer TP, Baldus WP. Hemosiderosis in cirrhosis: a study of 447 native livers. Gastroenterology 1997;112:882-888
69. Deugnier Y, Turlin B, Le Quilleuc D, et al.. A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of hemochromatosis. Am J Surg Pathol 1997;21:669-675
70. Deugnier YM, Guyader D, Crantock L, et al.. Primary liver cancer in genetic hemochromatosis: a clinical, pathological and pathogenetic study of 54 cases. Gastroenterology 1993;104:228-234
71. Deugnier YM, Charalambous P, Le Quilleuc D, et al. Preneoplastic significance of hepatic iron-free foci in genetic hemochromatosis: a study of 185 patients. Hepatology 1993;18:1363-1369
72. Blumberg RS, Chopra S, Ibrahim R, et al. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. Gastroenterology 1988;95:1399-1402
73. Bottomley SS. Secondary iron overload disorders. Semin Hematol 1998;35:77-86
74. Gordeuk V, Mukabi J, Hasstedt J, et al. Iron overload in Africa: interaction between a gene and dietary iron content. N Engl J Med 1992;326:95-100
75. Mandishona E, MacPhail AP, Gordeuk VR, et al. Dietary iron overload as a risk factor for hepatocellular carcinoma in black Africans. Hepatology 1998;27:1563-1566
76. Andrews NC. Disorders of iron metabolism. N Engl J Med 1999;341:1986-1995
77. Wurapa RK, Gordeuk VR, Brittenham GM, Khiyami A, Schechter GP, Edwards CQ. Primary iron overload in African Americans. Am J Med 1996;101:9-18
78. Barton JC, Edwards CQ, Bertoli LF, Shroyer TW, Hudson SL. Iron overload in African Americans. Am J Med 1995;99:616-623
79. Brown KE, Khan CM, Zimmerman B, Brunt EM. Hepatic iron overload in blacks and whites: a comparative autopsy study. Am J Gastroenterol 2003;98:1594-1598
80. Sindram JW, Marx JJM. Localization of iron in the hepatic acini and the bile duct epithelium as a tool for estimation of liver iron overload. Ann NY Acad Sci 1988;526:361-362
81. Rowe JW, Wands JR, Mezey E, et al. Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred. Medicine 1977;56:197-211
82. Searle J, Leggett BA, Crawford DHG, Powell LW. Iron storage diseases. In: MacSween RNM, Anthony PP, Scheuer PJ, Portmann BC, Burt AD, Ishak KG, eds. Pathology of the Liver. London, UK: Churchill Livingstone; 2002:257-272
83. Brissot P, Bourel M, Herry D, et al. Assessment of liver iron content in 271 patients: a reevaluation of direct and indirect methods. Gastroenterology 1981;80:557-565
84. Olynyk J, Hall P, Sallie R, Reed W, Shilkin K, Mackinnon M. Computerized measurement of iron in liver biopsies: a comparison with biochemical iron measurement. Hepatology 1990;12:26-30