Гемохроматоз – современное состояние проблемы
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В лекции освящены основные вопросы патогенеза, диагностики и лечения гемохроматоза. Приведено собственное клиническое наблюдение.
Ключевые слова: наследственный гемохроматоз, лечение, кровопускание.
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The iron overload syndrome can be associated with various acquired states and hereditary factors. Hereditary hemochromatosis is the most common genetic disorder. Without therapeutic intervention the disease can lead to the development of life-threatening complications such as cirrhosis, hepatocellular carcinoma. The article presents data on pathogenesis, diagnosis and treatment of hereditary hemochromatosis. Own clinical observation is given.
Keywords: hereditary haemochromatosis, treatment, phlebotomy.
2. Adams P, Brissot P, Powell L.W. EASL International consensus conference on haemochromatosis. Journal of Hepatology. 2000;33:487-496. https://doi.org/10.1016/s0168-8278(01)80874-6
3. Bacon ВR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatolog. 2011; 54: 328-343. https://doi.org/10.1002/hep.24330
4. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematologica. 2009; 122: 78–86. https://doi.org/10.1159/000243791
5. Nemeth E. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004; 306: 2090-2093. https://doi.org/10.1126/science.1104742
6. Ganz T. Iron homeostasis: fitting the puzzle pieces together. Cell Metabolism. 2008; 7 (4): 288-290. https://doi.org/10.1016/j.cmet.2008.03.008
7. 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. Nature Genetics. 1996;13:399-408. https://doi.org/ 10.1038/ng0896-399
8. Bardou-Jacquet E, de Tayrac M, Mosser J, Deugnier Y. GNPAT variant associated with severe iron overload in HFE hemochromatosis. Hepatology. 2015; 62 (6): 1917-1918. https://doi.org/10.1002/hep.27854
9. Adams PC, Barton JC, McLaren GD, Acton RT, Speechley M, McLaren CE et al. Screening for iron overload: lessons from the Hemochromatosis and IRon Overload Screening (HEIRS) Study. Canadian Journal of Gastroenterolgy. 2009; 23 (11): 769-772. https://doi.org/10.1155/2009/ 839308
10. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD et al. Hemochromatosis and iron-overload screening in a racially diverse population. New England Journal of Medicine. 2005; 352(17): 1769-1778. https://doi.org/10.1056/nejmoa041534
11. Philippe MA. Role of iron in hepatic fibrosis: one piece in the puzzle. World J Gastroenterol. 2007; 13 (35):4746. https://doi.org/10.3748/ wjg.v13.i35.4746
12. Allen KJ et al. Iron-overload-related disease in HFE hereditary hemo- chromatosis. New England Journal of Medicine. 2008; 358 (21): 2293-2295. https://doi.org/10.1056/nejmc080330
13. Asberg A, Hveem K, Thorstensen K. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001;36(10):1108-1115. https://doi.org/10.1080/003655201750422747
14. Warne CD, Zaloumis SG, Bertalli NA, Delatycki MB et al. HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype-stratified cohort study of hemochromatosis in Australian women. J Gastroenterol Hepatol. 2017; 32 (4): 797-802. https://doi.org/10.1111/jgh.13621
15. Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet. 2016; 388(10045): 706-716. https://doi.org/10.1016/s0140-6736(15) 01315-x
16. Wood MJ, Crawford DHG, Wockner LF, Powell LW, Ramm GA. Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis. Liver International. 2017; 37(9): 1382-1388. https://doi.org/10.1111/liv.13395
17. Allen KJ, Gurrin LC, Constantine CC et al. Iron-overload-disease in HFE hereditary hemochromatosis. New England Journal of Medicine. 2008; 358 (21): 2293-2295. https://doi.org/10.1056/nejmc080330
18. Allen KJ et al. HFE C282Y homozygotes with serum ferritin concentrations below 1000 lg/l are et low risk of hemochromatosis. Hepatology. 2010; 52 (3): 925-933. https://doi.org/10.1002/hep.23786
19. Moretti D, van Doorn GM, Swinkels DW, Melse-Boonstra A. Relevance of dietary iron intake and bioavailability in the management of HFE hemochromatosis: a systematic review. American Journal of Clinical Nutricion. 2013; 98 (2): 468-479. https://doi.org/10.3945/ ajcn.112.048264
20. Harrison-Findik DD, Schafer D, Klein E et al. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. Journal of Biological Chemistry. 2006; 281 (32): 22974-22982. https://doi.org/10.1074/ jbc.m602098200
21. Harrison-Findik DD, Klein E, Crist C, Evans J, Timchenko N, Gollan J. Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol. Hepatology. 2007;46(6):1979-1985. https://doi.org/10.1002/hep.21895
22. Delatycki MB, Gurrin LC, Ong SY et al. Reduced mortality due to phlebotomy in moderately iron-loaded HFE haemochromatosis? The need for clinical trials. Journal of Hepatology. 2015;63(1):282-283. https://doi.org/10.1016/j.jhep.2015.03.028
23. Stefashyna O, Stern M, Infanti L, Holbro A et al. Pattern of care of blood donors with early-uncomplicated hereditary haemochromatosis in a Swiss blood donation centre. Vox Sanguinis. 2013;106(2):111-117. https://doi.org/10.1111/vox.12078
24. Phatak P, Brissot P, Wurster M et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010;52(5):1671-1779. https://doi.org/ 10.1002/hep.23879
25. Rombout-Sestrienkova E, van Kraaij MGJ, Koek GH. How we manage patients with hereditary haemochromatosis. British Journal of Haematology. 2016; 175(5): 759-770. https://doi.org/10.1111/bjh.14376
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1. EASL clinical practice guidelines for HFE hemochromatosis. Journal of Hepatology. 2010; 53: 3-22. https://doi.org/10.1016/j.jhep.2010.03.001
2. Adams P, Brissot P, Powell L.W. EASL International consensus conference on haemochromatosis. Journal of Hepatology. 2000;33:487-496. https://doi.org/10.1016/s0168-8278(01)80874-6
3. Bacon ВR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatolog. 2011; 54: 328-343. https://doi.org/10.1002/hep.24330
4. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematologica. 2009; 122: 78–86. https://doi.org/10.1159/000243791
5. Nemeth E. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004; 306: 2090-2093. https://doi.org/10.1126/science.1104742
6. Ganz T. Iron homeostasis: fitting the puzzle pieces together. Cell Metabolism. 2008; 7 (4): 288-290. https://doi.org/10.1016/j.cmet.2008.03.008
7. 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. Nature Genetics. 1996;13:399-408. https://doi.org/ 10.1038/ng0896-399
8. Bardou-Jacquet E, de Tayrac M, Mosser J, Deugnier Y. GNPAT variant associated with severe iron overload in HFE hemochromatosis. Hepatology. 2015; 62 (6): 1917-1918. https://doi.org/10.1002/hep.27854
9. Adams PC, Barton JC, McLaren GD, Acton RT, Speechley M, McLaren CE et al. Screening for iron overload: lessons from the Hemochromatosis and IRon Overload Screening (HEIRS) Study. Canadian Journal of Gastroenterolgy. 2009; 23 (11): 769-772. https://doi.org/10.1155/2009/ 839308
10. Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD et al. Hemochromatosis and iron-overload screening in a racially diverse population. New England Journal of Medicine. 2005; 352(17): 1769-1778. https://doi.org/10.1056/nejmoa041534
11. Philippe MA. Role of iron in hepatic fibrosis: one piece in the puzzle. World J Gastroenterol. 2007; 13 (35):4746. https://doi.org/10.3748/ wjg.v13.i35.4746
12. Allen KJ et al. Iron-overload-related disease in HFE hereditary hemo- chromatosis. New England Journal of Medicine. 2008; 358 (21): 2293-2295. https://doi.org/10.1056/nejmc080330
13. Asberg A, Hveem K, Thorstensen K. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001;36(10):1108-1115. https://doi.org/10.1080/003655201750422747
14. Warne CD, Zaloumis SG, Bertalli NA, Delatycki MB et al. HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype-stratified cohort study of hemochromatosis in Australian women. J Gastroenterol Hepatol. 2017; 32 (4): 797-802. https://doi.org/10.1111/jgh.13621
15. Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet. 2016; 388(10045): 706-716. https://doi.org/10.1016/s0140-6736(15) 01315-x
16. Wood MJ, Crawford DHG, Wockner LF, Powell LW, Ramm GA. Serum ferritin concentration predicts hepatic fibrosis better than hepatic iron concentration in human HFE-Haemochromatosis. Liver International. 2017; 37(9): 1382-1388. https://doi.org/10.1111/liv.13395
17. Allen KJ, Gurrin LC, Constantine CC et al. Iron-overload-disease in HFE hereditary hemochromatosis. New England Journal of Medicine. 2008; 358 (21): 2293-2295. https://doi.org/10.1056/nejmc080330
18. Allen KJ et al. HFE C282Y homozygotes with serum ferritin concentrations below 1000 lg/l are et low risk of hemochromatosis. Hepatology. 2010; 52 (3): 925-933. https://doi.org/10.1002/hep.23786
19. Moretti D, van Doorn GM, Swinkels DW, Melse-Boonstra A. Relevance of dietary iron intake and bioavailability in the management of HFE hemochromatosis: a systematic review. American Journal of Clinical Nutricion. 2013; 98 (2): 468-479. https://doi.org/10.3945/ ajcn.112.048264
20. Harrison-Findik DD, Schafer D, Klein E et al. Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression. Journal of Biological Chemistry. 2006; 281 (32): 22974-22982. https://doi.org/10.1074/ jbc.m602098200
21. Harrison-Findik DD, Klein E, Crist C, Evans J, Timchenko N, Gollan J. Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol. Hepatology. 2007;46(6):1979-1985. https://doi.org/10.1002/hep.21895
22. Delatycki MB, Gurrin LC, Ong SY et al. Reduced mortality due to phlebotomy in moderately iron-loaded HFE haemochromatosis? The need for clinical trials. Journal of Hepatology. 2015;63(1):282-283. https://doi.org/10.1016/j.jhep.2015.03.028
23. Stefashyna O, Stern M, Infanti L, Holbro A et al. Pattern of care of blood donors with early-uncomplicated hereditary haemochromatosis in a Swiss blood donation centre. Vox Sanguinis. 2013;106(2):111-117. https://doi.org/10.1111/vox.12078
24. Phatak P, Brissot P, Wurster M et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010;52(5):1671-1779. https://doi.org/ 10.1002/hep.23879
25. Rombout-Sestrienkova E, van Kraaij MGJ, Koek GH. How we manage patients with hereditary haemochromatosis. British Journal of Haematology. 2016; 175(5): 759-770. https://doi.org/10.1111/bjh.14376
1 Новосибирский государственный медицинский университет ФГБОУ ВО НГМУ Минздрава России, Новосибирск, Россия;
2 Новосибирская городская клиническая больница №2, Новосибирск, Россия
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N.B. VOLOSHINА 1, M.F. OSIPENKO 1, N.V. LITVINOVA 1, A.N.VOLOSHIN 2
1 Novosibirsk State Medical University FGBOU in the NSMU of the Ministry of Health of Russia, Russia;
2 Novosibirsk City Clinical Hospital 2, Russia