Iron overload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance

World Journal of Gastroenterology

Volumn 13, Issue 35, 2007, Pages 4699-4706

  Kohgo, Yutaka ^a   Ikuta, Katsuya ^a   Ohtake, Takaaki ^a   Torimoto, Yoshihiro ^a   Kato, Junji ^a  

^a ASAHIKAWA MEDICAL COLLEGE   (Japan)

Author keywords

Alcohol; Chronic hepatic C; Cofactors; Hepatocellular carcinoma; Insulin resistance; Iron overload; Non alcoholic steatohepatitis

Indexed keywords

ALPHA INTERFERON; HEPCIDIN; RIBAVIRIN;

ALCOHOL CONSUMPTION; ALCOHOL LIVER DISEASE; ARTICLE; DIET RESTRICTION; HEPATITIS C; HUMAN; INSULIN RESISTANCE; IRON ABSORPTION; IRON METABOLISM; IRON OVERLOAD; LIVER CELL CARCINOMA; LIVER DISEASE; NONALCOHOLIC FATTY LIVER; NONHUMAN; PHLEBOTOMY; PORPHYRIA CUTANEA TARDA; RISK FACTOR;

EID: 34648813431     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v13.i35.4699     Document Type: Article

References (84)

1. Alla V, Bonkovsky HL. Iron in nonhemochromatotic liver disorders. Semin Liver Dis 2005; 25: 461-472
2. Chitturi S, George J. Interaction of iron, insulin resistance, and nonalcoholic steatohepatitis. Curr Gastroenterol Rep 2003; 5: 18-25
3. Ortiz V, Berenguer M, Rayon JM, Carrasco D, Berenguer J. Contribution of obesity to hepatitis C-related fibrosis progression. Am J Gastroenterol 2002; 97: 2408-2414
4. Barton JC, EdwardsCQ. Hemochromatosis. Cambridge University Press, 2000: 435-467
5. Cohen AR. New advances in iron chelation therapy. Hematology Am Soc Hematol Educ Program 2006; 42-47
6. Kono S, Suzuki H, Takahashi K, Takahashi Y, Shirakawa K, Murakawa Y, Yamaguchi S, Miyajima H. Hepatic iron overload associated with a decreased serum ceruloplasmin level in a novel clinical type of aceruloplasminemia. Gastroenterology 2006; 131: 240-245
7. Powell LW. Normal human iron storage and its relation to ethanol consumption. Australas Ann Med 1966; 15: 110-115
8. Kohgo Y, Ohtake T, Ikuta K, Suzuki Y, Hosoki Y, Saito H, Kato J. Iron accumulation in alcoholic liver diseases. Alcohol Clin Exp Res 2005; 29: 189S-193S
9. Takada A, Takase S, Tsutsumi M. Characteristic features of alcoholic liver disease in Japan: a review. Gastroenterol Jpn 1993; 28: 137-148
10. Bacon BR, Britton RS. The pathology of hepatic iron overload: a free radical - mediated process? Hepatology 1990; 11: 127-137
11. Uchida K, Szweda LI, Chae HZ, Stadtman ER. Immunochemical detection of 4-hydroxynonenal protein adducts in oxidized hepatocytes. Proc Natl Acad Sci USA 1993; 90: 8742-8746
12. Niemela O. Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress. Front Biosci 1999; 4: D506-D513
13. Pietrangelo A, Gualdi R, Casalgrandi G, Geerts A, De Bleser P, Montosi G, Ventura E. Enhanced hepatic collagen type I mRNA expression into fat-storing cells in a rodent model of hemochromatosis. Hepatology 1994; 19: 714-721
14. Ohhira M, Ohtake T, Matsumoto A, Saito H, Ikuta K, Fujimoto Y, Ono M, Toyokuni S, Kohgo Y. Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases. Alcohol Clin Exp Res 1998; 22: 145S-149S
15. Shaw S, Jayatilleke E. The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. Life Sci 1992; 50: 2045-2052
16. Kurose I, Higuchi H, Kato S, Miura S, Ishii H. Ethanol-induced oxidative stress in the liver. Alcohol Clin Exp Res 1996; 20: 77A-85A
17. Tsukamoto H, Horne W, Kamimura S, Niemela O, Parkkila S, Yla-Herttuala S, Brittenham GM. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest 1995; 96: 620-630
18. Xiong S, She H, Sung CK, Tsukamoto H. Iron-dependent activation of NF-kappaB in Kupffer cells: a priming mechanism for alcoholic liver disease. Alcohol 2003; 30: 107-113
19. French SW. Intragastric ethanol infusion model for cellular and molecular studies of alcoholic liver disease. J Biomed Sci 2001; 8: 20-27
20. Fujimoto M, Uemura M, Nakatani Y, Tsujita S, Hoppo K, Tamagawa T, Kitano H, Kikukawa M, Ann T, Ishii Y, Kojima H, Sakurai S, Tanaka R, Namisaki T, Noguchi R, Higashino T, Kikuchi E, Nishimura K, Takaya A, Fukui H. Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: relation to severity of liver disturbance. Alcohol Clin Exp Res 2000; 24: 48S-54S
21. Hirayama M, Kohgo Y, Kondo H, Shintani N, Fujikawa K, Sasaki K, Kato J, Niitsu Y. Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron. Hepatology 1993; 18: 874-880
22. Kobune M, Kohgo Y, Kato J, Miyazaki E, Niitsu Y. Interleukin-6 enhances hepatic transferrin uptake and ferritin expression in rats. Hepatology 1994; 19: 1468-1475
23. Ganz T. Hepcidin - a peptide hormone at the interface of innate immunity and iron metabolism. Curr Top Microbiol Immunol 2006; 306: 183-198
24. Ikuta K, Zak O, Aisen P. Recycling, degradation and sensitivity to the synergistic anion of transferrin in the receptor-independent route of iron uptake by human hepatoma (HuH-7) cells. Int J Biochem Cell Biol 2004; 36: 340-352
25. Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR. Pathophysiology of hereditary hemochromatosis. Semin Liver Dis 2005; 25: 411-419
26. Wallace DF, Summerville L, Lusby PE, Subramaniam VN. First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin. Gut 2005; 54: 980-986
27. Breuer W, Hershko C, Cabantchik ZI. The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci 2000; 23: 185-192
28. Suzuki Y, Saito H, Suzuki M, Hosoki Y, Sakurai S, Fujimoto Y, Kohgo Y. Up-regulation of transferrin receptor expression in hepatocytes by habitual alcohol drinking is implicated in hepatic iron overload in alcoholic liver disease. Alcohol Clin Exp Res 2002; 26: 26S-31S
29. Suzuki M, Fujimoto Y, Suzuki Y, Hosoki Y, Saito H, Nakayama K, Ohtake T, Kohgo Y. Induction of transferrin receptor by ethanol in rat primary hepatocyte culture. Alcohol Clin Exp Res 2004; 28: 98S-105S
30. Shindo M, Torimoto Y, Saito H, Motomura W, Ikuta K, Sato K, Fujimoto Y, Kohgo Y. Functional role of DMT1 in transferrin-independent iron uptake by human hepatocyte and hepatocellular carcinoma cell, HLF. Hepatol Res 2006; 35: 152-162
31. Ponka P, Lok CN. The transferrin receptor: role in health and disease. Int J Biochem Cell Biol 1999; 31: 1111-1137
32. Mullner EW, Kuhn LC. A stem-loop in the 3′ untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell 1988; 53: 815-825
33. Hentze MW, Kuhn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci USA 1996; 93: 8175-8182
34. Li CJ, Nanji AA, Siakotos AN, Lin RC. Acetaldehyde-modified and 4-hydroxynonenal-modified proteins in the livers of rats with alcoholic Liver disease. Hepatology 1997; 26: 650-657
35. Cairo G, Pietrangelo A. Nitric-oxide-mediated activation of iron-regulatory protein controls hepatic iron metabolism during acute inflammation. Eur J Biochem 1995; 232: 358-363
36. Philpott CC, Haile D, Rouault TA, Klausner RD. Modification of a free Fe-S cluster cysteine residue in the active iron-responsive element-binding protein prevents RNA binding. J Biol Chem 1993; 268: 17655-17658
37. Duane P, Raja KB, Simpson RJ, Peters TJ. Intestinal iron absorption in chronic alcoholics. Alcohol Alcohol 1992; 27: 539-544
38. Kulaksiz H, Gehrke SG, Janetzko A, Rost D, Bruckner T, Kallinowski B, Stremmel W. Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut 2004; 53: 735-743
39. Bridle K, Cheung TK, Murphy T, Walters M, Anderson G, Crawford DG, Fletcher LM. Hepcidin is down-regulated in alcoholic liver injury: implications for the pathogenesis of alcoholic liver disease. Alcohol Clin Exp Res 2006; 30: 106-112
40. Ohtake T, Saito H, Hosoki Y, Inoue M, Miyoshi S, Suzuki Y, Fujimoto Y, Kohgo Y. Hepcidin is down-regulated in alcohol loading. Alcohol Clin Exp Res 2007; 31: S2-S8
41. Harrison-Findik DD, Schafer D, Klein E, Timchenko NA, Kulaksiz H, Clemens D, Fein E, Andriopoulos B, Pantopoulos K, Gollan J. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. J Biol Chem 2006; 281: 22974-22982
42. http://www.healthyarkansas.com/services/C_Training/edu/Glossary/ default.htm
43. Shan Y, Lambrecht RW, Bonkovsky HL. Association of hepatitis C virus infection with serum iron status: analysis of data from the third National Health and Nutrition Examination Survey. Clin Infect Dis 2005; 40: 834-841
44. Farinati F, Cardin R, De Maria N, Della Libera G, Marafin C, Lecis E, Burra P, Floreani A, Cecchetto A, Naccarato R. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol 1995; 22: 449-456
45. Hayashi H, Takikawa T, Nishimura N, Yano M, Isomura T, Sakamoto N. Improvement of serum aminotransferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron. Am J Gastroenterol 1994; 89: 986-988
46. Yano M, Hayashi H, Yoshioka K, Kohgo Y, Saito H, Niitsu Y, Kato J, Iino S, Yotsuyanagi H, Kobayashi Y, Kawamura K, Kakumu S, Kaito M, Ikoma J, Wakusawa S, Okanoue T, Sumida Y, Kimura F, Kajiwara E, Sata M, Ogata K. A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan. J Gastroenterol 2004; 39: 570-574
47. Van Thiel DH, Friedlander L, Fagiuoli S, Wright HI, Irish W, Gavaler JS. Response to interferon alpha therapy is influenced by the iron content of the liver. J Hepatol 1994; 20: 410-415
48. Fontana RJ, Israel J, LeClair P, Banner BF, Tortorelli K, Grace N, Levine RA, Fiarman G, Thiim M, Tavill AS, Bonkovsky HL. Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial. Hepatology 2000; 31: 730-736
49. Di Bona D, Cippitelli M, Fionda C, Camma C, Licata A, Santoni A, Craxi A. Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway. J Hepatol 2006; 45: 271-279
50. Kohgo Y, Torimoto Y, Kato J. Transferrin receptor in tissue and serum: updated clinical significance of soluble receptor. Int J Hematol 2002; 76: 213-218
51. Mozer-Lisewska I, Mania A, Kowala-Piaskowska A, Figlerowicz M, Sluzewski W. Alterations of soluble transferrin receptor level in children with chronic hepatitis C during treatment with recombinant interferon-alpha and ribavirin. Hepatol Res 2005; 33: 19-23
52. Bonkovsky HL, Naishadham D, Lambrecht RW, Chung RT, Hoefs JC, Nash SR, Rogers TE, Banner BF, Sterling RK, Donovan JA, Fontana RJ, Di Bisceglie AM, Ghany MG, Morishima C. Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C. Gastroenterology 2006; 131: 1440-1451
53. Piperno A, Sampietro M, D'Alba R, Roffi L, Fargion S, Parma S. Nicoli C, Corbetta N, Pozzi M, Arosio V, Boari G, Fiorelli G. Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C. Liver 1996; 16: 248-254
54. Guyader D, Boucher E, Andre P, Even C, Cottereau J, Bianchi A, Gasser P, Mendler MH, Deugnier Y, Brissot P. A pilot study of iron depletion as adjuvant therapy in chronic hepatitis C patients not responding to interferon. Am J Gastroenterol 1999; 94: 1696-1698
55. Theurl I, Zoller H, Obrist P, Datz C, Bachmann F, Elliott RM, Weiss G. Iron regulates hepatitis C virus translation via stimulation of expression of translation initiation factor 3. J Infect Dis 2004; 190: 819-825
56. Xiong S, She H, Takeuchi H, Han B, Engelhardt JF, Barton CH, Zandi E, Giulivi C, Tsukamoto H. Signaling role of intracellular iron in NF-kappaB activation. J Biol Chem 2003; 278: 17646-17654
57. Saito H, Fujimoto Y, Ohtake T, Suzuki Y, Sakurai S, Hosoki Y, Ikuta K, Torimoto Y, Kohgo Y. Up-regulation of transferrin receptor 1 in chronic hepatitis C: Implication in excess hepatic iron accumulation. Hepatol Res 2005; 31: 203-210
58. Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med 2006; 57: 331-347
59. Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, Gombart AF, Koeffler HP. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J Biol Chem 1999; 274: 20826-20832
60. Kawabata H, Fleming RE, Gui D, Moon SY, Saitoh T, O'Kelly J, Umehara Y, Wano Y, Said JW, Koeffler HP. Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 2005; 105: 376-381
61. Takeo M, Kobayashi Y, Fujita N, Urawa N, Iwasa M, Horiike S, Tanaka H, Kaito M, Adachi Y. Upregulation of transferrin receptor 2 and ferroportin 1 mRNA in the liver of patients with chronic hepatitis C. J Gastroenterol Hepatol 2005; 20: 562-569
62. Mifuji R, Kobayashi Y, Ma N, Qiang QL, Urawa N, Horiike S, Iwasa M, Kaito M, Malavasi F, Adachi Y. Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C. J Gastroenterol Hepatol 2006; 21: 144-151
63. Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005; 102: 1906-1910
64. Inamura J, Ikuta K, Jimbo J, Shindo M, Sato K, Torimoto Y, Kohgo Y. Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines. Hepatol Res 2005; 33: 198-205
65. Aoki CA, Rossaro L, Ramsamooj R, Brandhagen D, Burritt MF, Bowlus CL. Liver hepcidin mRNA correlates with iron stores, but not inflammation, in patients with chronic hepatitis C. J Clin Gastroenterol 2005; 39: 71-74
66. Nagashima M, Kudo M, Chung H, Ishikawa E, Hagiwara S, Nakatani T, Dote K. Regulatory failure of serum prohepcidin levels in patients with hepatitis C. Hepatol Res 2006; 36: 288-293
67. Kato J, Kohgo Y, Sugawara N, Katsuki S, Shintani N, Fujikawa K, Miyazaki E, Kobune M, Takeichi N, Niitsu Y. Abnormal hepatic iron accumulation in LEC rats. Jpn J Cancer Res 1993; 84: 219-222
68. Kato J, Kobune M, Kohgo Y, Sugawara N, Hisai H, Nakamura T, Sakamaki S, Sawada N, Niitsu Y. Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats. J Clin Invest 1996; 98: 923-929
69. Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998; 4: 1065-1067
70. Furutani T, Hino K, Okuda M, Gondo T, Nishina S, Kitase A, Korenaga M, Xiao SY, Weinman SA, Lemon SM, Sakaida I, Okita K. Hepatic iron overload induces hepatocellular carcinoma in transgenic mice expressing the hepatitis C virus polyprotein. Gastroenterology 2006; 130: 2087-2098
71. Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, Banner BF. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 421-429
72. Harrison SA, Kadakia S, Lang KA, Schenker S. Nonalcoholic steatohepatitis: what we know in the new millennium. Am J Gastroenterol 2002; 97: 2714-2724
73. Washington K, Wright K, Shyr Y, Hunter EB, Olson S, Raiford DS. Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver. Hum Pathol 2000; 31: 822-828
74. George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, Jazwinska EC, Powell LW. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114: 311-318
75. Nakashima T, Sumida Y, Furutani M, Hirohama A, Okita M, Mitsuyoshi H, Itoh Y, Okanoue T. Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis. Hepatol Res 2005; 33: 135-137
76. Konishi M, Iwasa M, Araki J, Kobayashi Y, Katsuki A, Sumida Y, Nakagawa N, Kojima Y, Watanabe S, Adachi Y, Kaito M. Increased lipid peroxidation in patients with non-alcoholic fatty liver disease and chronic hepatitis C as measured by the plasma level of 8-isoprostane. J Gastroenterol Hepatol 2006; 21: 1821-1825
77. Malaguarnera L, Madeddu R, Palio E, Arena N, Malaguarnera M. Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients. J Hepatol 2005; 42: 585-591
78. Piperno A, Vergani A, Salvioni A, Trombini P, Vigano M, Riva A, Zoppo A, Boari G, Mancia G. Effects of venesections and restricted diet in patients with the insulin-resistance hepatic iron overload syndrome. Liver Int 2004; 24: 471-476
79. Yamamoto M, Iwasa M, Iwata K, Kaito M, Sugimoto R, Urawa N, Mifuji R, Konishi M, Kobayashi Y, Adachi Y. Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2007; 22: 498-503
80. Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, Taioli E, Valenti L, Fiorelli G. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 2448-2455
81. Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B, Iannelli A, Staccini-Myx A, Casanova D, Ben Amor I, Saint-Paul MC, Huet PM, Sadoul JL, Gugenheim J, Srai SK, Tran A, Le Marchand-Brustel Y. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006; 131: 788-796
82. Sumida Y, Kanemasa K, Fukumoto K, Yoshida N, Sakai K, Nakashima T, Okanoue T. Effect of iron reduction by phlebotomy in Japanese patients with nonalcoholic steatohepatitis: A pilot study. Hepatol Res 2006; 36: 315-321
83. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134-140
84. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 2005; 54: 533-539