Disorders of iron overload

MacSween's Pathology of the Liver

Volumn , Issue , 2012, Pages 261-292

  Paterson, Alan C ^a   Pietrangelo, Antonello ^b  

^a Ampath Trust   (South Africa)

^b UNIVERSITY OF MODENA AND REGGIO EMILIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84882851401     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-7020-3398-8.00005-2     Document Type: Chapter

References (331)

1. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class 1-like gene is mutated in patients with hereditary HC. Nat Genet 1996, 13:399-408.
2. Cook JD, Barry WE, Hershko C, et al. Iron kinetics with emphasis on iron overload. Am J Pathol 1973, 72:337-343.
3. Andrews NC Disorders of iron metabolism. N Engl J Med 1999, 341:1986-1995.
4. Conrad ME, Umbreit JN Pathways of iron absorption. Blood Cells Mol Dis 2002, 29:336-355.
5. Fleming RE Advances in understanding the molecular basis for the regulation of dietary iron absorption. Gastroenterol 2005, 21:201-206.
6. Roy CN, Enns CA Iron homeostasis: new tales from the crypt. Blood 2000, 96:4020-4027.
7. McKie AT, Latunde-Dada GO, Miret S, et al. Molecular evidence for the role of a ferric reductase in iron transport. Biochem Soc Trans 2002, 30:722-724.
8. Grushin H, Mackenzie B, Berger UV, et al. Cloning and characterisation of a mammalian proton-coupled metal-iron transporter. Nature 1997, 388:482-488.
9. Uc A, Stokes JB, Britigan BE Haem transport exhibits polarity in Caco-2 cells: evidence for an active and membrane protein-mediated process. Am J Physiol Gastrointest Liver Physiol 2004, 287:G1150-G1157.
10. Quigley JG, Yang Z, Worthington MT, et al. Identification of a human haem exporter that is essential for erythropoiesis. Cell 2004, 118:757-766.
11. Umbreit JN, Conrad ME, Moore EG, et al. Iron absorption and cellular transport: the mobilferrin/paraferritin paradigm. Semin Hematol 1998, 35:13-26.
12. Aboud S, Haile DJ A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 2000, 275:19906-19912.
13. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 2000, 403:776-781.
14. McKie AT, Marciani P, Rolfs A, et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000, 5:299-309.
15. Andrews NC Molecular control of iron metabolism. Best Prac Res Clin Haemol 2005, 18:159-169.
16. Vulpe CD, Kuo YM, Murphy TL, et al. Hephaestin, a caeruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999, 21:195-199.
17. Harris ZL, Durley AP, Man TK, et al. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci USA 1999, 96:10812-10817.
18. Heeney MM, Andrews NC Iron homeostasis and inherited iron overload disorders: an overview. Hematol Oncol Clin North Am 2004, 18:1-20.
19. Cheng Y, Zak O, Alsen P, et al. Structure of the transferrin receptor - transferrin complex. Cell 2004, 116:565-576.
20. Hagar W, Theil E, Vichinsky EP Diseases of iron metabolism. Ped Clin N Am 2002, 49:893-909.
21. Glockner G, Scherer S, Schattevoy R, et al. Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes. Genome Res 1998, 8:1060-1073.
22. Kawabata H, Yang R, Hirama T, et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 1999, 274:20826-20832.
23. Kawabata H, Germain RS, Vuong PT, et al. Transferrin receptor 2-alpha supports cell growth in both iron-chelated cultured cells and in vivo. J Biol Chem 1999, 275:1668-16625.
24. Griffiths WJ, Cox TM Co-localization of the mammalian HC gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells. J Histochem Cytochem 2003, 51:613-624.
25. West AP, Bennett MJ, Sellers VM, et al. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary HC protein HFE. J Biol Chem 2000, 275:38135-38138.
26. Goswami T, Andrews NC Hereditary HC protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem 2006, 281:28494-28498.
27. Chen J, Chloupková M, Gao J, et al. HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1-HFE interactions. J Biol Chem 2007, 282:36862-36870.
28. Waheed A, Britton RS, Grubb JH, et al. HFE association with transferrin receptor 2 increases cellular uptake of transferrin-bound iron. Arch Biochem Biophys 2008, 474:193-197.
29. Levy JE, Jin O, Fujiwara Y, et al. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet 1999, 21:396-399.
30. Fleming RE, Ahmann JR, Migas MC, et al. Targeted mutagenesis of the murine transferrin receptor-2 gene produces HC. Proc Natl Acad Sci USA 2002, 99:10653-10658.
31. Bratosin D, Mazurier J, Tissier JP, et al. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. A review. Biochimie 1998, 80:173-195.
32. Knutson MD, Vafa MR, Haile DJ, et al. Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages. Blood 2003, 102:4191-4197.
33. Thiel E Ferritin: at the crossroads of iron and oxygen metabolism. J Nutr 2003, 133:1549S-1553S.
34. Hentze MW, Muckenthaler M, Andrews NC Balancing acts: molecular control of iron metabolism. Cell 2004, 117:285-297.
35. Rouault TA Post-transcriptional regulation of human iron metabolism by iron regulatory proteins. Blood Cell Mol Dis 2002, 29:309-314.
36. Beutler E 'Pumping' iron: the proteins. Science 2004, 306:2051-2053.
37. Salahudeen AA, Thompson JW, Ruiz JC, et al. An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science 2009, 326:722-726.
38. Vashisht AA, Zumbrennen KB, Huang X, et al. Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science 2009, 326:718-721.
39. Finch C Regulators of iron balance in humans. Blood 1994, 84:1697-1702.
40. Andrews NC Iron metabolism: iron deficiency and iron overload. Ann Rev Genom and Hum Genet 2000, 1:75-98.
41. Krause A, Neitz S, Magert HJ, et al. LEAP-1, a novel highly disulphide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000, 480:147-150.
42. Park CH, Valore EV, Waring AJ, et al. Hepcidin, a urinary antimicrobial protein synthesized by the liver. J Biol Chem 2001, 276:7806-7810.
43. Vecchi C, Montosi G, Zhang K, et al. ER stress controls iron metabolism through induction of hepcidin. Science 2009, 325:877-880.
44. Hunter HN, Fulton GB, Ganz T, et al. The solution structure of hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary HC. J Biol Chem 2002, 277:37597-37603.
45. Nemeth E, Valore EV, Territo M, et al. Hepcidin, a putative mediator of anemia of inflammation is a type II acute-phase protein. Blood 2002, 101:2461-2463.
46. Lee P, Peng H, Gelbart T, et al. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005, 102:1906-1910.
47. Pigeon C, Ilyin G, Courselaud B, et al. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001, 276:7811-7819.
48. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in Upstream Stimulator 2 (USF2) knockout mice. Proc Natl Acad Sci USA 2001, 98:8780-8785.
49. Nicolas G, Bennoun M, Porteu A, et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002, 99:4596-4601.
50. Papanikolaou G, Tzilianos M, Christakis JI, et al. Hepcidin in iron overload disorders. Blood 2005, 105:4103-4105.
51. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulated cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004, 306:2090-2093.
52. Wang RH, Li C, Xu X, et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2005, 2:399-409.
53. Babitt JL, Huang FW, Wrighting DM, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 2006, 38:531-539.
54. Babitt JL, Huang FW, Xia Y, et al. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest 2007, 117:1933-1939.
55. Yu PB, Hong CC, Sachidanandan C, et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 2008, 4:33-41.
56. Andriopoulos B, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 2009, 41:482-487.
57. Meynard D, Kautz L, Darnaud V, et al. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 2009, 41:478-481.
58. McCord JM Iron, free radicals, and oxidative injury. Semin Haematol 1998, 35:5-12.
59. Papanikolaou G, Pantopolous K Iron metabolism and toxicity. Toxicol Appl Pharm 2005, 202:199-211.
60. Pietrangelo A Hemochromatosis: an endocrine liver disease. Hepatology 2007, 46:1291-1301.
61. Adams PC Hemochromatosis. Clin Liv Dis 2004, 8:735-753.
62. Hemochromatosis. Online Mendelian Inheritance in Man database Available at, Accessed August 2010. http://www.ncbi.nlm.nih.gov/omim.
63. Pietrangelo A, Caleffi A, Henrion J, et al. Juvenile HC associated with pathogenic mutations of adult HC genes. Gastroenterology 2005, 128:470-479.
64. Pietrangelo A Hereditary HC - a new look at an old disease. N Engl J Med 2004, 350:2383-2397.
65. Trousseau A Glycosurie: diabete sucre. Clinique medicale de l'Hotel-Dieu de Paris 1865, 663-698. editors, J.-B. Bailliere, Paris.
66. Troisier M Diabète sucré. Bull Soc Anat Paris 1871, 44:231-235.
67. von Recklinghausen FD Uber Haemochromatose. Tageblatt Versammlung Dtsche Naturforscher Arzte Heidelberg 1889, 62:324-325.
68. Reuben A Landmarks in Hepatology: praise ye the god of iron. Hepatology 2004, 40:1231-1234.
69. Sheldon JH Haemochromatosis. The Bradshaw lecture. Lancet 1934, 2:1031-1036.
70. Simon M, Bourel M, Fauchet R, et al. Association of HLA A3 and HLAB14 antigens with idiopathic HC. Gut 1976, 17:332-334.
71. Simon M, Alexandre JL, Bourel M, et al. Heredity of idiopathic HC: a study of 106 families. Clin Genet 1977, 11:327-341.
72. de Sousa M, Reimao R, Lacerda R, et al. Iron overload in beta 2-microglobulin-deficient mice. Immunol Lett 1994, 39:105-111.
73. Santos M, Schilham MW, Rademakers LH, et al. Defective iron homeostasis in beta2-microglobulin knockout mice recapitulates hereditary HC in man. J Exp Med 1996, 184:1975-1985.
74. Xhou XY, Tomatsu S, Fleming RE, et al. HFE knockout produces mouse model of hereditary HC. Proc Natl Acad Sci USA 1998, 95:2492-2497.
75. Levy JE, Montross LK, Cohen DE, et al. The C282 mutation causing hereditary HC does not produce a null allele. Blood 1999, 94:9-11.
76. Pietrangelo A, Montosi G, Totaro A, et al. Hereditary HC in adults without pathogenic mutations in the HC gene. N Engl J Med 1999, 341:725-732.
77. Montosi G, Donovan A, Totaro A, et al. Autosomal-dominant HC is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest 2001, 108:619-623.
78. Camaschella C, Roetto A, Calì A, et al. The gene TFR2 is mutated in a new type of HC mapping to 7q22. Nat Genet 2000, 25:14-15.
79. Roetto A, Papanikolaou G, Politou M, et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile HC. Nat Genet 2003, 33:21-22.
80. Papanikolaou G, Samuels ME, Ludwig EH, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile HC. Nat Genet 2004, 36:77-82.
81. Lamon JM, Marynick SP, Rosenblatt R, Donnelly S Idiopathic HC in a young female: a case study and review of the syndrome in young people. Gastroenterology 1979, 76:178-183.
82. Finch SC, Finch CA Idiopathic HC, an iron storage disease. Medicine (Baltimore) 1955, 34:381-430.
83. Camaschella C, Roetto A, Cicilano M, et al. Juvenile and adult HC are distinct genetic disorders. Eur J Hum Genet 1997, 5:371-375.
84. Roetto A, Totaro A, Gazzola M, et al. Juvenile HC locus maps to chromosome 1q. Am J Hum Genet 1999, 64:1388-1393.
85. Daraio F, Ryan E, Gleeson A, et al. Juvenile HC due to G320V/Q116X compound heterozygosity of hemojuvelin in an Irish patient. Blood, Cells Mol Dis 2005, 35:174-176.
86. Gehrke SG, Pietrangelo A, Kascak M, et al. HJV gene mutations in European patients with juvenile HC. Clin Genet 2005, 67:425-438.
87. Roetto A, Daraio F, Poporato P, et al. Screening hepcidin for mutations in juvenile HC: identification of a new mutation (C70R). Blood 2004, 103:2407-2409.
88. Biassiotto G, Roetto A, Daraio F, et al. Identification of new mutations of hepcidin and hemojuvelin in patients with HFE C282Y allele. Blood Cells Mol Dis 2004, 33:338-343.
89. Jacolot S, Le Gac G, Scotet V, et al. HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype. Blood 2004, 103:2835-2840.
90. Le Gac G, Scotet V, Ka C, et al. The recently identified type 2A juvenile HC gene (HJV), a second candidate modifier of the C282Y homozygous phenotype. Hum Mol Gen 2004, 13:1913-1918.
91. Holmstrom P, Marmur J, Eggertsen G, et al. Mild iron overload in patients carrying the HFE S65C gene mutation: a retrospective study in patients with suspected iron overload and healthy controls. Gut 2002, 51:723-730.
92. Mura COR, Ferec C HFE mutation analysis in HC probands: evidence of S65C implication in mild form of HC. Blood 1999, 711:2502-2505.
93. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ Global prevalence of putative HC mutations. J Med Genet 1997, 34:275-278.
94. Lucotte G Celtic origin of the C282Y mutation of HC. Blood 1998, 24:433-438.
95. Distante S, Robson KJH, Graham-Campbell J, et al. The origin and spread of the HFE-C282Y HC mutation. Hum Genet 2004, 115:269-279.
96. Gochee PA, Powell LW, Cullen DJ, et al. A population-based study of the biochemical and clinical expression of the H63D HC mutation. Gastroenterology 2002, 122:646-651.
97. Rossi E, Olynyk JK, Cullen DJ, et al. Compound heterozygous HC genotype predicts increased iron and erythrocyte indices in women. Clin Chem 2000, 46:162-166.
98. Lim EM, Rossi E, De Boer WB, et al. Hepatic iron loading in patients with compound heterozygous HFE mutations. Liver Int 2004, 24:631-636.
99. Walsh A, Dixon JL, Ramm GA, et al. The clinical relevance of compound heterozygosity for the C282Y and H63D substitutions in HC. Clin Gastroenterol Hepatol 2006, 4:1403-1410.
100. Camaschella C Why do humans need two types of transferrin receptor? Lessons from a rare genetic disorder. Haematologica 2005, 90:296.
101. Mattman A, Huntsman D, Lockitch G, et al. Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood 2002, 100:1075-1077.
102. Camaschella C, Fargion S, Sampietro M, et al. Inherited HFE-unrelated HC in Italian families. Hepatology 1999, 29:1563-1564.
103. Roetto A, Totaro A, Piperno A, et al. New mutations inactivating transferrin receptor 2 in HC type 3. Blood 2001, 97:2555-2560.
104. Girelli D, Roetto A, Daraio F, et al. Clinical and pathologic findings in HC type 3 due to a novel mutation in transferrin receptor 2 gene. Gastroenterology 2002, 122:1295-1302.
105. Hattori A, Wakusawa S, Hayashi H, et al. AVAQ 594-597 deletion of the TfR2 gene in a Japanese family with HC. Hepatol Res 2003, 26:154-156.
106. Koyama Wakusawa S, Hayashi H, et al. Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with HC. Haematologica 2005, 90:302-307.
107. Beutler L, Beutler E Hematologically important mutations: iron storage diseases. Blood Cell Mol Dis 2004, 33:40-44.
108. Lanzara C, Roetto A, Daraio F, et al. Spectrum of hemojuvelin gene mutations in 1q-linked juvenile HC. Blood 2004, 103:4317-4321.
109. Pietrangelo A The ferroportin disease. Blood Cells Mol Dis 2004, 32:131-138.
110. Njajou N, Vaessen M, Joosse B, et al. mutation in SLC11A3 is associated with autosomal dominant HC. Nat Genet 2001, 28:213-214.
111. Wallace DF, Clark RM, Harley HAJ, Subramaniam VN Autosomal dominant iron overload due to a novel mutation of ferroportin1 associated with parenchymal iron loading and cirrhosis. J Hepatol 2004, 40:710-713.
112. Sham RL, Pradyumna D, Phatak PD, et al. Autosomal dominant hereditary HC associated with a novel ferroportin mutation and unique clinical features. Blood Cells Mol Dis 2005, 34:157-161.
113. Corradini E, Garuti C, Montosi G, et al. Bone morphogenetic protein signaling is impaired in an HFE knockout mouse model of HC. Gastroenterology 2009, 137:1489-1497.
114. Kautz L, Meynard D, Besson-Fournier C, et al. BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression. Blood 2009, 114:2515-2520.
115. Wallace DF, Summerville L, Crampton EM, et al. Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload. Hepatology 2009, 50:1992-2000.
116. Adams P, Brissot P, Powell LW International consensus conference on HC. J Hepatol 2000, 33:487-496.
117. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005, 352:1769-1778.
118. Beutler E, Felitti VJ, Koziol JA, et al. Penetrance of the 845G to A (C282Y) HFE hereditary HC mutation in the USA. Lancet 2002, 359:211-218.
119. Fleming RE, Britton RS, Waheed A, et al. Pathogenesis of hereditary HC. Clin Liv Dis 2004, 8:755-773.
120. Brittenham GM, Farrell DE, Harris JW, et al. Magnetic-susceptibility measurement of human iron stores. N Engl J Med 1982, 307:1671-1675.
121. Pietrangelo A Non-invasive assessment of hepatic iron overload: are we finally there?. J Hepatol 2005, 42:153-154.
122. St.Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005, 105:855-861.
123. Deugnier YM, Charalambous P, Le Quilleuc D, et al. Preneoplastic significance of hepatic iron-free foci in genetic HC: a study of 185 patients. Hepatology 1993, 18:1363-1369.
124. Adams PC, Barton JC How I treat HC. Blood 2010, 116:317-325.
125. Fargion S, Fracanzani AL, Piperno A, et al. Prognostic factors for HCC in genetic HC. Hepatology 1994, 20:1426-1431.
126. Kowdley KV Iron, HC, and HCC. Gastroenterology 2004, 127:S79-S86.
127. Bomford A, Williams R Long term results of venesection therapy in idiopathic HC. Q J Med 1976, 45:611-623.
128. Niederau C, Fischer R, Purschel A, et al. Long-term survival in patients with hereditary HC. Gastroenterology 1996, 110:1107-1119.
129. Waalen J, Nordestgaard BG, Beutler E The penetrance of hereditary HC. Best Pract Res Clin Haem 2005, 18:203-220.
130. Nemeth E, Roetto A, Garozzo G, et al. Hepcidin is decreased in TFR2 HC. Blood 2005, 105:1803-1806.
131. Cox TM, Halsall DJ Hemochromatosis - neonatal and young subjects. Blood Cells Mol Dis 2002, 29:411-417.
132. Filali M, Le Jeunne C, Durand E, et al. Juvenile HC HJV-related revealed by cardiac shock. Blood Cells Mol Dis 2004, 33:120-124.
133. Kelly AL, Rhodes DA, Roland JM, et al. Hereditary juvenile HC: a genetically herogeneous life-threatening iron storage disease. Q J Med 1998, 91:607-618.
134. De Domenico I, Ward DM, Nemeth E, et al. The molecular basis of ferroportin-linked HC. Proc Natl Acad Sci USA 2005, 102:8955-8960.
135. Eason RJ, Adams PC, Aston CE, Searle J Familial iron overload with possible autosomal dominance. Aust NZ Med J 1990, 20:226-230.
136. Arden KE, Wallace DF, Dixon DL, et al. A novel mutation in ferroportin1 is associated with HC in a Solomon Islands patient. Gut 2003, 52:1215-1217.
137. Rivard SR, Lanzara C, Grimard D, et al. Autosomal dominant reticuloendothelial iron overload (HFE type 4) due to a new missense mutation in the ferroportin 1 gene (SLC11A3) in a large French-Canadian family. Haematologica 2003, 88:824-826.
138. Viprakasit V, Merryweather-Clarke A, Chinthammitr Y, et al. Molecular diagnosis of the first ferroportin mutation (C326Y) in the far east causing a dominant form of inherited iron overload (abstract). Blood 2004, 104:3204.
139. Aguilar-Martinez P, Schved JF, Brissot P The evaluation of hyperferritinemia: an updated strategy based on advances in detecting genetic abnormalities. Am J Gastroenterol 2005, 100:1185-1194.
140. Allerson CR, Cazzola M, Rouault TA Clinical severity and thermodynamic effects of iron-responsive element mutations in Hereditary Hyperferritinemia-Cataract Syndrome. J Biol Chem 1999, 274:26439-26447.
141. Beaumont C, Leneuve P, Devaux I, et al. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat Genet 1995, 11:444-446.
142. Kato J, Fujikawa K, Kanda M, et al. A mutation in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J Hum Genet 2001, 69:191-197.
143. Ferreira C, Santambrogio P, Martin ME, et al. H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. Blood 2001, 98:525-532.
144. Siah CW, Trinder D, Olynyk JK Iron overload. Clin Chim Acta 2005, 358:24-36.
145. Heilmeyer L, Keller W, Vivell O, et al. Die kongenitale Atransferrinämie. Schweiz Med Wochenschr 1961, 91:1203.
146. Beutler E, Gelbart T, Lee P, et al. Molecular characterization of a case of atransferrinemia. Blood 2000, 96:4071-4074.
147. Knisely AB, Gelbart T, Beutler E Molecular characterization of a third case of human atransferrinaemia (letter). Blood 2004, 104:2607.
148. Hayashi A, Wada Y, Suzuki T, Shimizu A Studies on familial hypotransferrinemia: a unique clinical course and molecular pathology. Am J Hum Genet 1993, 53:201-213.
149. Trenor CC, Campagna DR, Sellers VM, et al. The molecular defect in hypotransferrinemic mice. Blood 2000, 96:1113-1118.
150. Royle NJ, Irwin DM, Koschinsky ML, et al. Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-3q24, respectively. Somat Cell Mol Genet 1998, 13:285-292.
151. Harris ZL, Takahashi Y, Miyajima H, et al. Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci USA 1995, 92.
152. Yoshida K, Furihata K, Takeda S, et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 1995, 9:267-272.
153. Hellman NE, Schaefer M, Gehrke S, et al. Hepatic iron overload in aceruloplasminemia. Gut 2000, 47:858-860.
154. Bosio S, De Gobbi M, Roetto A, et al. Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations. Blood 2002, 100:2246-2248.
155. Hellman NE, Kono S, Miyajima H, Gitlin JD Biochemical analysis of a missense mutation in aceruloplasminemia. J Biol Chem 2002, 277:1375-1380.
156. Hardy L, Hansen JL, Kushner JP, Knisely AS Neonatal HC: genetic analysis of transferrin-receptor, H-apoferritin, and L-apoferritin loci and of the human leukocyte antigen class 1 region. Am J Pathol 1990, 137:149-153.
157. Murray KF, Kowdley KV Neonatal HC. Pediatrics 2001, 108:960-964.
158. Knisely AS, Mieli-Vergani G, Whitington PF Neonatal HC. Gastroenterol Clin North Am 2003, 32:877-889.
159. Kelly AL, Lunt PW, Rodrigues F, et al. Classification and genetic features of neonatal HC: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. J Med Genet 2001, 38:599-610.
160. Flynn DM, Mohan N, McKiernan P, et al. Progress in treatment and outcome for children with neonatal HC. Arch Dis Child Fetal Neonatal Ed 2003, 88:124-127.
161. Whitington PF, Hibbard JU High-dose immunoglobulin during pregnancy for recurrent neonatal HC. Lancet 2004, 364:1690-1698.
162. Knisely AS, O'Shea PA, Stocks JF, Dimmick JE Oropharyngeal and upper respiratory gland mucosal-gland siderosis in neonatal HC: an approach to biopsy diagnosis. J Pediatr 1988, 113:871-874.
163. Andrews NC, Anupindi S, Badizadegan K Case records of the Massachusetts General Hospital. Case 21-2005. A four-week-old male infant with jaundice and thrombocytopenia. N Engl J Med 2005, 353:189-198.
164. Oddone M, Bellini C, Bonacci W, et al. Diagnosis of neonatal HC with MR imaging and duplex Doppler sonography. Eur Radiol 1999, 9:1882-1885.
165. Bellini C, Mazzella M, Scopesi F, Serra G Spontaneous recovery in neonatal HC. J Hepatol 2004, 41:882-883.
166. Inui A, Fujisawa T, Kubo T, et al. A case of neonatal HC-like liver failure with spontaneous remission. J Pediatr Gastroenterol Nutr 2005, 40:374-377.
167. Sigurdsson L, Reyes J, Kocoshis SA, et al. Neonatal HC: outcomes of pharmacologic and surgical therapies. J Pediatr Gastroenterol Nutr 1998, 26:85-89.
168. Egawa H, Bergquist W, Garcia-Kennedy R, et al. Rapid development of hepatocellular siderosis after transplantation for neonatal HC. Transplantation 1996, 62:1511-1513.
169. Whitington PF, Kelly S Outcome of pregnancies at risk for neonatal HC is improved by treatment with IVIG. Pediatrics 2008, 121:e1615-e1621.
170. Rand EB, Karpen SJ, Kelly S, et al. Treatment of neonatal HC with exchange transfusuon and intravenous immunoglobulin. J Pediatr 2009, 155:566-571.
171. Pan X, Kelly S, Melin-Aldana H, et al. Novel mechanism of fetal hepatocyte injury in congenital alloimmune hepatitis involves the terminal complelement cascade. Hepatology 2010, 51:2061-2068.
172. Knisely AS, Vergani D 'Neonatal hepatitis': a re-vision. Hepatology 2010, 51:1888-1890.
173. Dehner LP, Snover DC, Sharp HL, et al. Hereditary tyrosinemia type I (chronic form): pathologic findings in the liver. Hum Pathol 1989, 20:149-159.
174. Danks DM, Tippett P, Adams C, et al. Cerebro-hepato-renal syndrome of Zellweger: a report of eight cases with comments upon the incidence, the liver lesion, and a fault of pipecolic acid metabolism. J Pediatr 1975, 86:382-387.
175. Sharma R, Hudak ML, Perszyk AA, et al. Perinatal lethal form of Gaucher's disease presenting with hemosiderosis. Am J Perinatol 2000, 17:201-206.
176. Gurakan B, Ozbek N, Varan B, et al. Fatal acidosis in a neonate with Pearson syndrome. Turk J Pediatr 1999, 41:361-364.
177. Bioulac-Sage P, Parrot-Roulaud F, Mazat JP, et al. Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation deficiency): a light and electron microscopic study of the liver. Hepatology 1993, 18:839-846.
178. Gordeuk VR, McLaren CE, MacPhail AP, et al. Associations of iron overload in Africa with HCC and tuberculosis: Strachan's 1929 thesis revisited. Blood 1996, 87:3470-3476.
179. MacPhail AP, Simon MO, Torrance JD, et al. Changing patterns of dietary iron overload in black South Africans. Am J Clin Nutr 1979, 32:1272-1278.
180. Friedman BM, Baynes RD, Bothwell TH, et al. Dietary iron overload in southern African rural blacks. S Afr Med J 1990, 78:301-305.
181. Gordeuk VR African iron overload. Semin Hematol 2002, 39:263-269.
182. Gordeuk VR, Boyd RD, Brittenham GM Dietary iron overload persists in rural sub-Saharan Africa. Lancet 1986, 1:1310-1313.
183. Walker ARP, Arvidsson UB Iron overload in the South African Bantu. Trop Roy Soc Trop Med Hyg 1953, 47:536-548.
184. Bothwell TH, Bradlow BA Siderosis in the Bantu. A combined histopathological and chemical study. Arch Path 1960, 70:279-292.
185. Bothwell TH, Seftel H, Jacobs P, et al. Iron overload in Bantu subjects. Studies on the availability of iron in Bantu beer. Am J Clin Nutrit 1964, 14:47-51.
186. Moyo VM, Gangaidzo IT, Gomo ZA, et al. Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe. Blood 1997, 89:2159-2166.
187. Gordeuk V, Mukiibi J, Hasstedt SJ, et al. Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 1992, 326:95-100.
188. Moyo VM, Mandishona E, Hasstedt SJ, et al. Evidence of genetic transmission in African iron overload. Blood 1998, 91:1076-1082.
189. McNamara L, MacPhail AP, Gordeuk VR, et al. Is there a link between African iron overload and the described mutations of the hereditary HC gene?. Br J Haematol 1998, 102:1176-1178.
190. Wurapa RK, Gordeuk VR, Brittenham GM, et al. Primary iron overload in African Americans. Am J Med 1996, 101:9-18.
191. Beutler E, Barton JC, Felitti VJ, et al. Ferroportin 1 (SCL40A1) variant associated with iron overload in African-Americans. Blood Cells Mol Dis 2003, 31:305-309.
192. Gordeuk VR, Caleffi A, Corradini E, et al. Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells Mol Dis 2003, 31:299-304.
193. McNamara L, Gordeuk VR, MacPhail AP Ferroportin (Q248H) mutations in African families with dietary iron overload. J Gastroenterol Nutr 2005, 20:1855-1858.
194. Bothwell TH, Isaacson C Siderosis in the bantu. A comparison of incidence in males and females. Br Med J 1962, 1:522-524.
195. Isaacson C, Seftel HC, Keeley KJ, Bothwell TH Siderosis in the Bantu: The relationship between iron overload and cirrhosis. J Lab Clin Med 1962, 58:845-853.
196. Seftel HC, Keeley KJ, Isaacson C, Bothwell TH Siderosis in the Bantu: The clinical incidence of HC in diabetic subjects. J Lab Clin Med 1961, 58:837-844.
197. Seftel HC, Malkin C, Schmaman A, et al. Osteoporosis, scurvy and siderosis in Johannesburg Bantu. Br Med J 1966, 1:642-646.
198. Wapnick AA, Lynch SR, Seftel HC, et al. The effect of siderosis and ascorbic acid depletion on bone metabolism with special reference to osteoporosis in the Bantu. Br J Nutr 1971, 25:367-376.
199. Bothwell TH, Abrahams C, Bradlow BA, Charlton RW Idiopathic and Bantu HC. Arch Pathol 1965, 79:163-168.
200. Paterson AC, MacPhail AP, Goedeuk VR African iron overload revisited: histology in relation to measurements of iron status (abstract). Hepatology 1999, 30(suppl):382A.
201. MacPhail AP, Mandishona EM, Bloom PD, et al. Measurements of iron status and survival in African iron overload. S Afr Med J 1999, 89:966-972.
202. Mandishona E, MacPhail PA, Gordeuk VR, et al. Dietary iron overload as a risk factor for HCC in Black Africans. Hepatology 1998, 27:1563-1566.
203. Mims MP, Guan Y, Pospisilova D, et al. Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood 2005, 105:1337-1342.
204. Huang FW, Pinkus JL, Pinkus GS, et al. A mouse model of juvenile HC. J Clin Invest 2005, 115:2187-2191.
205. Pietrangelo A Non-HFE HC. Hepatology 2004, 39:21-29.
206. Lo L, Singer ST Thalassemia: current approach to an old disease. Pediatr Clin N Am 2002, 49:1165-1191.
207. Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferroxamine in preventing complications of iron overload in patients with thalassaemia major. N Engl J Med 1994, 331:567-573.
208. Modell B, Khan M, Darlison M Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 2000, 355:2051-2052.
209. Martins R, Picanco I, Fonseca A, et al. The role of HFE mutations on iron metabolism in beta-thalassemia carriers. J Hum Genet 2004, 49:651-655.
210. Origa R, Gakanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 2007, 92:583-588.
211. Nemeth E Targetting the hepcidin-ferroportin axis in the diagnosis and treatment of anemias. Adv Hematol 2010, 2010:750643.
212. Camberlein E, Zanninelli G, Detivaud L, et al. Anemia in β-thalassemiapatients targets hepatic hepcidin transacript levels independently of iron metabolism genes controlling hepcidin expression. Haematologica 2008, 93:111-115.
213. De Franceschi L, Daraio F, Filippini A, et al. Liver expression of hepcidin and other iron genes in two mouse models of beta-thalassemia. Haematologica 2006, 91:1336-1342.
214. Longo F, Zecchina G, Sbaiz L, et al. The influence of HC mutations on iron overload of thalassemia major. Haematologica 1999, 84:799-803.
215. Riva A, Mariani R, Bovo G, et al. Type 3 HC and beta-thalassemia trait. J Haematol 2004, 72:370-374.
216. Camaschella C Understanding iron homeostasis through genetic analysis of HC and related disorders. Blood 2005, 106:3710-3717.
217. Mancuso A, Sciarrino E, Renda MC, Maggio A A prospective study of HCC incidence in thalassemia. Hemoglobin 2006, 30:119-124.
218. Levi S, Corsi B, Bosisio M, et al. A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem 2001, 276:24437-24440.
219. Roy CN, Andrews NC Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum Mol Genet 2001, 10:2181-2186.
220. Napier I, Ponka P, Richardson DR Iron trafficking in the mitochondrion: novel pathways revealed by disease. Blood 2005, 105:1867-1874.
221. Online Mendelian Inheritance in Man, OMIM, X linked sideroblastic anemia, MIM ID #300751. 2000. McKusick Nathans Institute for Genetic Medicine, Baltimore, MD.
222. Peto TE, Pippard MJ, Weatherall DJ Iron overload in mild sideroblastic anaemias. Lancet 1983, 1:375-378.
223. Barron R, Grace ND, Sherwood G, Powell LW Iron overload complicating sideroblastic anemia - is the gene for HC responsible?. Gastroenterology 1989, 96:1204-1206.
224. Beris P, Samii K, Darbellay R, et al. Iron overload in patients with sideroblastic anaemia is not related to the presence of the HC Cys282Tyr and His63Asp mutations. Br J Haematol 1999, 104:97-99.
225. Cuijpers ML, Raymakers RA, Mackenzie MA, et al. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome. Br J Haematol 2010, 49:322-333.
226. Chemmanur AT, Bonkovsky HL Hepatic porphyrias: diagnosis and management. Clin Liver Dis 2004, 8:807-838.
227. Mehrany K, Drage LA, Brandhagen DJ, Pittelkow MR Association of porphyria cutanea tarda with hereditary HC. J Am Acad Dermatol 2004, 51:205-211.
228. Sampietro M, Fiorelli G, Fargion S Iron overload in porphyria cutanea tarda. Haematologica 1999, 84:248-253.
229. Bonkovsky HL, Poh-Fitzpatrick M, Pimstone N, et al. Porphyria cutanea tarda, hepatitis C, and HFE gene mutations in North America. Hepatology 1998, 21:1661-1669.
230. Ajioka RS, Phillips JD, Weiss RB, et al. Down-regulation of hepcidin in porphyria cutanea tarda. Blood 2008, 112:4723-4728.
231. Walker AP, Partridge J, Srai SK, Dooley JS Hepcidin: what every gastroenterologist should know. Gut 2004, 53:624-627.
232. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004, 113:1271-1276.
233. Rivera S, Liu L, Nemeth E, et al. Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. Blood 2005, 105:1797-1802.
234. Cheng PP, Jiao XY, Wang XH, et al. Hepcidin in anemia of chronic disease and concomitant iron deficiency anemia. Clin Exp Med 2010 May 25.
235. Ludwig J, Hashimoto E, Porayko MK, et al. Hemosiderosis in cirrhosis: a study of 447 native livers. Gastroenterology 1997, 112:882-888.
236. Pietrangelo A Iron in NASH, chronic liver diseases and HCC: how much iron is too much?. J Hepatol 2009, 50:249-251.
237. Bonkovsky HL, Banner BF, Rothman AL Iron and chronic viral hepatitis. Hepatology 1997, 25:759-768.
238. Uraz S, Aygun C, Sonsuz A, Ozbay G Serum iron levels and hepatic iron overload in nonalcoholic steatohepatitis and chronic viral hepatitis. Dig Dis Sci 2005, 50:964-969.
239. Mah YH, Kao JH, Liu CJ, et al. Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan. Liver Int 2005, 25:214-219.
240. Di Bisceglie AM, Axiotis CA, Hoofnagle JH, Bacon BR Measurements of iron status in patients with chronic hepatitis. Gastroenterology 1992, 102:2108-2113.
241. Cotler SJ, Bronner MP, Press RD, et al. End-stage liver disease without HC associated with elevated hepatic iron index. J Hepatol 1998, 29:257-262.
242. Hezode C, Cazeneuve C, Coue O, et al. Liver iron accumulation in patients with chronic active hepatitis C: prevalence and role of hemachromatosis gene mutations and relationships with hepatic histological lesions. J Hepatol 1999, 31:979-984.
243. Bonkovsky HL, Lambrecht RW, Shan Y Iron as a co-morbid factor in nonhaemochromatotic liver disease. Alcohol 2003, 30:137-144.
244. Eisenbach C, Gehrke SG, Stremmel W Iron, the HFE gene, and hepatitis C. Clin Liver Dis 2004, 8:775-785.
245. Kato J, Kobune M, Nakamura T, et al. Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. Cancer Res 2001, 61:8697-8702.
246. Yano M, Hayashi H, Wakusawa S, et al. Long term effects of phlebotomy on biochemical and histological parameters of chronic hepatitis C. Am J Gastroenterol 2002, 97:133-137.
247. Kakizaki S, Takagi H, Horiguchi N, et al. Iron enhances hepatitis C virus replication in cultured hepatocytes. Liver 2000, 20:125-128.
248. Aoki CA, Rossaro L, Ramsamooj R, et al. Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 2005, 39:71-74.
249. Girelli D, Pasino M, Goodnough JB, et al. Reduced serum hepcidin levels in chronic hepatitis C. J Hepatol 2009, 51:845-852.
250. Miura K, Taura K, Kodama Y, et al. Hepatitis C virus-induced oxidative stress suppresses hepcidin expresion through increased histone deactylase activity. Hepatology 2008, 48:1420-1429.
251. Vidali M, Tripodi MF, Ivaldi A, et al. Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C. J Hepatol 2008, 48:399-406.
252. Tung BY, Emond MJ, Bronner MP, et al. Hepatitis C, iron status, and disease severity: relationship with HFE mutations. Gastroenterology 2003, 124:318-326.
253. Valenti L, Pulixi EA, Arosio P, et al. Relative contributions of iron genes, dysmetabolism, and hepatitis C virus (HCV) in the pathogenesis of altered ironmetabolism in chronic HCV hepatitis. Haematologia 2007, 92:1037-1042.
254. Bataller R, North KE, Brenner DA Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal. Hepatology 2003, 37:493-503.
255. Gilbert A, Grenet A Cirrhose alcoolique hypertrophique pigmentaire. Compte Rendus Soc de Biol 1896, 10:1078-1081.
256. Conrad ME, Berman A, Brosby WH Iron kinetics in Laennec's cirrhosis. Gastroenterology 1962, 43:386-390.
257. Sabesin SM, Thomas LB Parenchymal siderosis in patients with preexisting portal cirrhosis. A pathological entity simulating idiopathic and transfusional HC. Gastroenterology 1964, 46:477-485.
258. MacDonald RA Primary HC: inherited or acquired?. Prog Hematol 1966, 5:324-353.
259. Bassett ML, Halliday JW, Powell LW Value of hepatic iron measurements in early HC and determination of the critical iron level associated with fibrosis. Hepatology 1986, 6:24-29.
260. Powell LW Iron storage in relatives of patients with HC and in relatives of patients with alcoholic cirrhosis and haemosiderosis. A comparative study of 27 families. Q J Med 1965, 34:427-442.
261. Fletcher LM, Dixon JL, Purdie DM, et al. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary HC: quantifying the risk. Gastroenterology 2002, 122:281-289.
262. Fletcher LM, Powell LW Hemochromatosis and alcoholic liver disease. Alcohol 2003, 30:131-136.
263. Ioannou GN, Dominitz JA, Weiss NS, et al. The effect of alcohol consumption on the prevalence of iron overload, irondeficiency, and iron deficiency anemia. Gastroenterogy 2004, 126:1293-1301.
264. Arteel GE Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 2003, 124:778-790.
265. Tavill AS, Qadri AM Alcohol and iron. Semin Liv Dis 2004, 24:317-325.
266. Pietrangelo A Iron-induced oxidant stress in alcoholic liver fibrogenesis. Alcohol 2003, 30:121-129.
267. Ohtake T, Saito H, Hosoki Y, et al. Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 2007, 31(1 Suppl):S2-S8.
268. Harrison-Findik DD Is the iron regulatory hormone hepacidin a risk factor for alcoholic liver disease?. World J Gastroenterol 2009, 15:1186-1193.
269. Swanson CA Iron intake and regulation: implications for iron deficiency and iron overload. Alcohol 2003, 30:99-102.
270. Ludwig J, Yiggiano TR, McGill DB, Ott BJ Nonalcoholic steatohepatitis. Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980, 55:434-438.
271. 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.
272. Bonkovsky H, Jawaid Q, Tortorelli K, 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.
273. Valenti L, Dongiovanni P, Fracanzani AL, et al. Increased susceptibility to nonalcoholic fatty liver disease in heterozygotes for the mutation responsible for hereditary HC. Dig Liv Dis 2003, 35:172-178.
274. Younossi ZM, Gramlich T, Bacon BR, et al. Hepatic iron and nonalcoholic fatty liver disease. Hepatology 1999, 30:847-850.
275. Angulo P, Keach JC, Batts KP, Lindor KD Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999, 30:1356-1362.
276. 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.
277. 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.
278. Marchesini G, Forlani G NASH: from liver diseases to metabolic disorders and back to clinical hepatology. Hepatology 2002, 35:497-499.
279. Duseja A, Das R, Nanda M, et al. Nonalcoholic steatohepatitis is neither associated with iron overload nor with HFE gene mutations. World J Gastroenterol 2005, 11:393-395.
280. Lee SH, Jeong SH, Lee D, et al. An epidemiologic study on the incidence and significance of HFE mutations in a Korean cohort with nonalcoholic fatty liver disease. J Clin Gastroenterol 2010, 44:e154-e161.
281. Raszeja-Wyszomirska J, Kurzwaski G, Lawniczak M, et al. Nonalcoholic fatty liver disease and HFE gene mutations: a study from Poland. World J Gastroenterol 2010, 16:2531-2536.
282. Weltman MD, Farrell GC, Hall P, et al. Hepatic cytochrome P450 2El is increased in patients with nonalcoholic steatohepatitis. Hepatology 1998, 27:128-133.
283. Valenti L, Fracanzani AL, Bugianesi E, et al. HFE phenotype, parenchymal Iron accumulation and liver fibrosis In patients with nonalcoholic fatty liver disease. Gastroenterology 2010, 138:905-912.
284. Brandhagen DJ, Alvarez W, Therneau M, et al. Iron overload in cirrhosis; HFE genotypes and outcome after liver transplantation. Hepatology 2000, 31:456-460.
285. Walker NM, Stuart KA, Ryan RJ, et al. Serum ferriting concentration predicts mortality in patients awaiting liver transplantation. Hepatology 2010, 51:1683-1691.
286. Fenton H, Torbenson M, Vivekanandan P, et al. Marked iron accumulation in liver explants in the absence of major gene defects of hereditary hemochromatosis: a risk factor for cardiac failure. Transplantation 2009, 187(8):1256-1260.
287. Ko C, Siddaiah N, Berger J, et al. Prevalence of hepatic Iron overload and association with hepatocellular carncer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry. Liver Int 2007, 27:1394-1401.
288. Brodanova M, Hoenig V Iron metabolism in patients with porta-caval shunts. Scand J Gastroenterol 1966, 1:167-172.
289. Conn HO Portacaval anastomosis and hepatic hemosiderin deposition: a prospective, controlled investigation. Gastroenterology 1972, 62:61-72.
290. Adams PC, Bradley C, Frei JV Hepatic iron and zinc concentrations after portacaval shunting for nonalcoholic cirrhosis. Hepatology 1994, 19:101-105.
291. Niederau C, Fischer R, Sonnenberg A, et al. Survival and causes of death in cirrhotic and noncirrhotic patients with primary HC. N Engl J Med 1985, 313:1256-1262.
292. Bradbear RA, Bain C, Siskind V, et al. Cohort study of internal malignancy in genetic HC and other chronic nonalcoholic liver diseases. J Natl Cancer Inst 1985, 75:81-84.
293. Adams PC Hepatocellular carcinoma in hereditary HC. Can J Gastorenterol 1993, 7:37-41.
294. Hsing AW, McLaughlin JK, Olsen JH, et al. Cancer risk following primary HC: a population-based cohort study in Denmark. Int J Cancer 1995, 60:160-162.
295. Fargion S, Mandelli C, Piperno A, et al. Survival and prognostic factors in 212 Italian patients with genetic HC. Hepatology 1992, 15:655-659.
296. Fracanzani AL, Conte D, Fraquelli M, et al. Increased cancer risk in a cohort of 230 patients with hereditary HC in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology 2001, 33:647-651.
297. Goh J, Callagy G, McEntee G, et al. Hepatocellular carcinoma arising in the absence of cirrhosis in genetic HC: three case reports and review of literature. Eur J Gastroenterol Hepatol 1999, 11:915-919.
298. Britto MR, Thomas LA, Balaratnam N, et al. Hepatocellular carcinoma arising in non-cirrhotic liver in genetic HC. Scand J Gastroenterol 2000, 35:889-893.
299. Morcos M, Dubois S, Bralet MP, et al. Primary carcinoma in genetic HC reveals a broad genetic spectrum. Am J Clin Pathol 2001, 116:738-843.
300. Blumberg RS, Chopra S, Ibrahim R, et al. Primary HCC in idiopathic HC after reversal of cirrhosis. Gastroenterology 1988, 95:1399-1402.
301. Deugnier YM, Guyader D, Crantock L, et al. Primary liver cancer in genetic HC: a clinical, pathological and pathogenetic study of 54 cases. Gastroenterology 1993, 104:228-234.
302. Deugnier Y Iron and liver cancer. Alcohol 2003, 30:145-150.
303. Linet MS, Gridley G, Nyren O, et al. Primary liver cancer, other malignancies, and mortality risks following porphyria: a cohort study in Denmark and Sweden. Am J Epidemiol 1999, 149:1010-1015.
304. Starley BQ, Calcaqno CJ, Harrison SA Nonalcoholic fatty liver disease and hepatocellular carcionoma: a weighty connection. Hepatology 2010, 51:1820-1832.
305. Sorrrentino P, D'Angelo S, Ferbo U, et al. Liver iron excess in patients with HCC developed on non-alcoholic steato-hepatitis. J Hepatol 2009, 50:351-357.
306. Higginson J Primary carcinoma of the liver in Africa. Br J Cancer 1956, 10:609-622.
307. Moyo VM, Makunike R, Gangaidzo IT, et al. African iron overload and HCC. Eur J Hematol 1998, 60:28-34.
308. Toyokuni S Iron-induced carcinogenesis: the role of redox regulation. Free Radic Biol Med 1996, 20:553-566.
309. Smith PG, Yeoh GCT Chronic iron overload in rats induces oval cells in the liver. Am J Pathol 1996, 149:389-398.
310. Pigeon C, Turlin B, Iancu TC, et al. Carbonyl-iron supplementation induces hepatocyte nuclear changes in BALB/CJ male mice. J Hepatol 1999, 30:926-934.
311. Rothenberg BE, Voland JR β2 Knockout mice develop parenchymal iron overload: a putative role for class I genes of the major histocompatibility complex in iron metabolism. Proc Natl Acad Sci USA 1996, 93:1529-1534.
312. Deugnier Y, Loréal O, Turlin B, et al. Liver pathology in genetic HC: a review of 135 homozygous patients and their bioclinical correlations. Gastroenterology 1992, 102:2050-2059.
313. Williams G, Yamamoto R Absence of stainable iron from preneoplastic and neoplastic lesions in rat liver with 8-hydroxyquinolone-induced siderosis. J Natl Cancer Inst 1972, 49:685-692.
314. Asare G, Paterson AC, Kew MC, et al. Development of iron free foci and HCC in the absence of cirrhosis in rats fed a diet high in iron. J Clin Pathol 2006, 208:82-90.
315. Stål P, Hultcrantz R, Moller L, Eriksson LC The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. Hepatology 1995, 21:521-528.
316. Turlin B, Deugnier Y Evaluation and interpretation of iron in the liver. Sem Diagn Pathol 1998, 15:237-245.
317. Harrison SA, Bacon BR Relation of HC with HCC: epidemiology, natural history, pathophysiology, screening, treatment, and prevention. Med Clin N Am 2005, 89:391-409.
318. Kew MC Hepatic iron overload and HCC. Cancer Lett 2009, 286:38-43.
319. Crawford DHG, Fletcher LM, Hubscher SG, et al. Patient and graft survival after liver transplantation for hereditary HC: implications for pathogenesis. Hepatology 2004, 39:1655-1662.
320. Dar FS, Faraj W, Zaman MB, et al. Outcome of liver transplantation in hereditary HC. Transpl Int 2009, 22:717-724.
321. Parolin MB, Batts KP, Weisner RH, et al. Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis. Liver Transpl 2002, 8:331-339.
322. Guyader D, Jacquelinet C, Moirand R, et al. Noninvasive prediction of fibrosis in C282Y homozygous HC. Gastroenterology 1998, 115:929-936.
323. Turlin B, Deugnier Y Iron overload disorders. Clin Liv Dis 2002, 6:481-496.
324. Scheuer PJ, Williams R, Muir A Hepatic pathology in relatives of patients with HC. J Pathol Bacteriol 1962, 84:53-64.
325. Brissot P, Bourel M, Herry D, et al. Asessment of liver iron content in 271 patients: reevaluation of direct and indirect methods. Gastroenterology 1981, 80:557-565.
326. Rappaport AM, Borowy ZI, Lougheed WM, Lotto WN Subdivision of hexagonal liver lobules into a structural and functional unit. Role in hepatic physiology and pathology. Anat Rec 1954, 119:11-34.
327. Deugnier YM, Turlin B, Powell LW, et al. Differentiation between heterozygotes and homozygotes HC by means of a histological hepatic iron index: a study of 192 cases. Hepatology 1993, 17:30-34.
328. Deugnier Y, Turlin B Pathology of hepatic iron overload. World J Gastroenterol 2007, 13:4755-4760.
329. Adams PC, Bradley C, Henderson AR Evaluation of the hepatic iron index as criterion for genetic HC a diagnostic criterion for genetic HC. J Lab Clin Med 1997, 130:509-514.
330. Deugnier Y, Turlin B, le Quilleuc D A reappraisal of hepatic siderosis in patients with end-stage cirrhosis: practical implications for the diagnosis of HC. Am J Surg Pathol 1997, 21. 699-675.
331. Sorrentino D, D'Angelo S, Ferbo U, et al. Liver iron excess in patients with HCC developed on non-alcoholic steatohepatitis. J Hepatol 2009, 50:351-357.