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Неалкогольная жировая болезнь печени и сахарный диабет типа 2
Неалкогольная жировая болезнь печени и сахарный диабет типа 2
Родионова С.В., Звенигородская Л.А., Бирюкова Е.В. Неалкогольная жировая болезнь печени и сахарный диабет типа 2. Consilium Medicum. 2016; 18 (8): 46–50. DOI: 10.26442/2075-1753_2016.8.46-50
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Аннотация
Сахарный диабет типа 2 (СД 2) часто сочетается с неалкогольной жировой болезнью печени (НАЖБП). Сочетание СД 2 и НАЖБП связано с высоким риском развития цирроза печени и гепатоцеллюлярной карциномы у данных больных. Все аспекты патогенеза НАЖБП до конца неизвестны, но ключевая роль отводится инсулинорезистентности. Новый класс пероральных сахароснижающих препаратов – ингибиторы натрий-глюкозного котранспортера 2-го типа (ингибиторы SGLT2) – снижают уровень гликемии независимым от инсулина способом. Ингибиторы SGLT2 приводят к уменьшению массы тела, следовательно, снижению инсулинорезистентности, гиперинсулинемии, а также нормализации синтеза глюкозы и ее утилизации в печени. Данный класс сахароснижающих препаратов может оказывать положительное влияние на НАЖБП и быть использован для лечения у пациентов с сочетанием СД 2 и НАЖБП.
Ключевые слова: неалкогольная жировая болезнь печени, неалкогольный стетогепатит, сахарный диабет типа 2, инсулинорезистентность.
Ключевые слова: неалкогольная жировая болезнь печени, неалкогольный стетогепатит, сахарный диабет типа 2, инсулинорезистентность.
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Diabetes mellitus type 2 (DM 2) is often associated with non-alcoholic fatty liver disease (NAFLD). The combination of type 2 diabetes and NAFLD is associated with a high risk of developing liver cirrhosis and hepatocellular carcinoma in patients with data. All aspects of the pathogenesis of NAFLD is unknown until the end, but a key role for insulin resistance. A new class of oral antidiabetic drugs – inhibitors of sodium-glucose cotransporter type 2 (inhibitors of SGLT2) – reduce the level of blood glucose independent of insulin manner. SGLT2 inhibitors lead to a decrease in body weight, thereby reducing insulin resistance, hyperinsulinemia, and glucose normalization synthesis and its utilization in the liver. This class of antidiabetic drugs may have positive effects on NAFLD and be used to treat patients with a combination of type 2 diabetes and NAFLD.
Key words: non-alcoholic fatty liver disease, non-alcoholic stetogepatit, type 2 diabetes mellitus, insulin resistance.
Key words: non-alcoholic fatty liver disease, non-alcoholic stetogepatit, type 2 diabetes mellitus, insulin resistance.
Полный текст
Список литературы
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28. InvokanaTM [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; March 2013.
29. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986; 292: 13–5.
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31. Fierbinteanu-Braticevici C, Dina I, Petrisor A et al. Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis. World J Gastroenterol 2010; 16: 4784–91.
32. Lamos EM, Younk LM, Davis SN. Canagliflozin, an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Exp Opin Drug Metab Toxicol 2013; 9 (6): 763–75.
33. Kleiner DE, Brunt EM, Van Natta M et al. Clinical research network. Design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 4: 1313–21.
34. Ratziu V, Bellentani S, Cortez-Pinto H et al. A position statement on NAFLD/NASH based on the EASL 2009 Special Conference. J Hepatol 2010; 53: 372–84.
35. Weyer C, Funahashi T, Tanaka S et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–5.
36. Ratziu V. Current and future insulin sensitizers in the treatment of NASH. EASL 2015, Vienna. http://ilc-congress.eu/pgc/ILC2015-PGC-Book.pdf
37. Trappoliere M, Caligiuri A, Schmid M. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol 2009; 50 (6): 1102–11.
38. Li Y, Liu L, Wang B et al. Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomed Rep 2013; 1 (1): 57–64.
39. Loomba R, Lutchman G, Kleiner DE et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alim Pharmacol Ther 2009; 29 (2): 172–82.
40. Haukeland JW, Konopski Z, Eggesbø HB et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 2009; 44 (7): 853–60.
41. Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol 2009; 46 (2): 113–8.
42. Lavine JE, Schwimmer JB, Molleston JP et al. Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemporary Clinical Trials 2010; 31 (1): 62–70.
43. Krakoff J, Clark JM, Crandall JP et al. Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity 2010; 18 (9): 1762–7.
2. Egorova E.N., Zvenigorodskaia L.A., Khomeriki S.G. Kliniko-morfologicheskie osobennosti porazheniia pecheni u bol'nykh s insulinorezistentnost'iu. Avtoref dis. … kand. med. nauk. M., 2008; s. 45–6. [in Russian]
3. Lazo M, Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008; 28 (4): 339–50.
4. AGA. The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142: 1592–609.
5. Browning JD, Szczepaniak LS, Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004; 40: 1387–95.
6. Lazo M, Hernaez R, Eberhardt MS et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 2013; 178: 38–45.
7. Ivashkin V, Drapkina O. The prevalence of non-alcoholic fatty liver disease in Russian Federation. Gut 2009; 58: 1207.
8. Fan JG, Farrell GC. Epidemiology of nonalcoholic fatty liver disease in China. J Hepatol 2009; 50: 204–10.
9. Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): A «growing» problem? J Hepatol 2007; 6: 1133–42.
10. Leite NC, Salles GF, Araujo A et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 2009; 29: 113–9.
11. Prashanth M, Ganesh HK, Vima MV et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India 2009; 57: 205–10.
12. Bedogni G, Miglioli L, Masutti F, Tiribelli C. Prevalence and risk factors for non-alcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44–52.
13. Brunt EM. Nonalcoholic steatohepatiatis. Semin Liver Dis 2004; 24: 3–20.
14. Pendino G, Mariano A, Surace P et al. Prevalence and etiology of altered liver tests: a population based survey in a Mediterranean town. Hepatology 2005; 41: 1151–9.
15. Ghouri N, Preiss D, Sattar N. Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data. Hepatology 2010; 52: 1156–61.
16. Sung KC, Kim SH. Interrelationship between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes. J Clin Endocrinol Metab 2011; 96 (4): 1093–7.
17. Roma MG, Toledo FD, Boaglio AC et al. Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clin Sci (Lond) 2011; 121: 523–44.
18. Babu A. Canagliflozin for the treatment of type 2 diabetes. Drugs Today (Barc) 2013; 49 (6): 363–76.
19. Polyzos SA, Kountouras J, Zavos C. Nonalcoholic Fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 2009; 9: 299–314.
20. Donnelly KL, Smith CI et al. Sources of fatty acids storet in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343–51.
21. Nisly SA, Kolanczyk DM, Walton AM. Canagliflozin, a new sodium-glucose cotransporter 2 inhibitor, in the treatment of diabetes. Am J Health Syst Pharm 2013; 70 (4): 311–9.
22. Fedorov I.G., Nikitin I.G., Storozhakov G.I. Nealkogol'nyi steatogepatit: klinika, patogenez, diagnostika, lechenie. Consilium Medicum. 2004. [in Russian]
23. Mc Cullough AJ. The epidemiology and risk factors of NASH. Hepatology 2013; 58 (5): 1644–54.
24. Moschetta A, Modica S, Gadaleta RM. Modulation of nuclear bile acid receptor FXR activity in the gut – liver axis. Nucl Recept Signal 2010; 8: 005.
25. Bedossa P. Current histological classification of NAFLD: strength and limitations. Hepatol Int 2013; 7 (Suppl. 2): S.765–70.
26. Ikura Y. Transitions of histopathologic criteria for diagnosis of nonalcoholic fatty liver disease during the last three decades. World J Hepatol 2014; 12 (6): 894–900.
27. Kleiner DE, Brunt EM, Van Natta M et al. Clinical research network. Design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313–21.
28. InvokanaTM [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; March 2013.
29. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986; 292: 13–5.
30. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatology 2013; 58: 1007–19.
31. Fierbinteanu-Braticevici C, Dina I, Petrisor A et al. Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis. World J Gastroenterol 2010; 16: 4784–91.
32. Lamos EM, Younk LM, Davis SN. Canagliflozin, an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Exp Opin Drug Metab Toxicol 2013; 9 (6): 763–75.
33. Kleiner DE, Brunt EM, Van Natta M et al. Clinical research network. Design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 4: 1313–21.
34. Ratziu V, Bellentani S, Cortez-Pinto H et al. A position statement on NAFLD/NASH based on the EASL 2009 Special Conference. J Hepatol 2010; 53: 372–84.
35. Weyer C, Funahashi T, Tanaka S et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–5.
36. Ratziu V. Current and future insulin sensitizers in the treatment of NASH. EASL 2015, Vienna. http://ilc-congress.eu/pgc/ILC2015-PGC-Book.pdf
37. Trappoliere M, Caligiuri A, Schmid M. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol 2009; 50 (6): 1102–11.
38. Li Y, Liu L, Wang B et al. Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomed Rep 2013; 1 (1): 57–64.
39. Loomba R, Lutchman G, Kleiner DE et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alim Pharmacol Ther 2009; 29 (2): 172–82.
40. Haukeland JW, Konopski Z, Eggesbø HB et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 2009; 44 (7): 853–60.
41. Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol 2009; 46 (2): 113–8.
42. Lavine JE, Schwimmer JB, Molleston JP et al. Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemporary Clinical Trials 2010; 31 (1): 62–70.
43. Krakoff J, Clark JM, Crandall JP et al. Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity 2010; 18 (9): 1762–7.
2. Егорова Е.Н., Звенигородская Л.А., Хомерики С.Г. Клинико-морфологические особенности поражения печени у больных с инсулинорезистентностью. Автореф дис. … канд. мед. наук. М., 2008; с. 45–6. / Egorova E.N., Zvenigorodskaia L.A., Khomeriki S.G. Kliniko-morfologicheskie osobennosti porazheniia pecheni u bol'nykh s insulinorezistentnost'iu. Avtoref dis. … kand. med. nauk. M., 2008; s. 45–6. [in Russian]
3. Lazo M, Clark J. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008; 28 (4): 339–50.
4. AGA. The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142: 1592–609.
5. Browning JD, Szczepaniak LS, Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology 2004; 40: 1387–95.
6. Lazo M, Hernaez R, Eberhardt MS et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 2013; 178: 38–45.
7. Ivashkin V, Drapkina O. The prevalence of non-alcoholic fatty liver disease in Russian Federation. Gut 2009; 58: 1207.
8. Fan JG, Farrell GC. Epidemiology of nonalcoholic fatty liver disease in China. J Hepatol 2009; 50: 204–10.
9. Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): A «growing» problem? J Hepatol 2007; 6: 1133–42.
10. Leite NC, Salles GF, Araujo A et al. Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 2009; 29: 113–9.
11. Prashanth M, Ganesh HK, Vima MV et al. Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. J Assoc Physicians India 2009; 57: 205–10.
12. Bedogni G, Miglioli L, Masutti F, Tiribelli C. Prevalence and risk factors for non-alcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44–52.
13. Brunt EM. Nonalcoholic steatohepatiatis. Semin Liver Dis 2004; 24: 3–20.
14. Pendino G, Mariano A, Surace P et al. Prevalence and etiology of altered liver tests: a population based survey in a Mediterranean town. Hepatology 2005; 41: 1151–9.
15. Ghouri N, Preiss D, Sattar N. Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data. Hepatology 2010; 52: 1156–61.
16. Sung KC, Kim SH. Interrelationship between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes. J Clin Endocrinol Metab 2011; 96 (4): 1093–7.
17. Roma MG, Toledo FD, Boaglio AC et al. Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications. Clin Sci (Lond) 2011; 121: 523–44.
18. Babu A. Canagliflozin for the treatment of type 2 diabetes. Drugs Today (Barc) 2013; 49 (6): 363–76.
19. Polyzos SA, Kountouras J, Zavos C. Nonalcoholic Fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 2009; 9: 299–314.
20. Donnelly KL, Smith CI et al. Sources of fatty acids storet in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343–51.
21. Nisly SA, Kolanczyk DM, Walton AM. Canagliflozin, a new sodium-glucose cotransporter 2 inhibitor, in the treatment of diabetes. Am J Health Syst Pharm 2013; 70 (4): 311–9.
22. Федоров И.Г., Никитин И.Г., Сторожаков Г.И. Неалкогольный стеатогепатит: клиника, патогенез, диагностика, лечение. Consilium Medicum. 2004. / Fedorov I.G., Nikitin I.G., Storozhakov G.I. Nealkogol'nyi steatogepatit: klinika, patogenez, diagnostika, lechenie. Consilium Medicum. 2004. [in Russian]
23. Mc Cullough AJ. The epidemiology and risk factors of NASH. Hepatology 2013; 58 (5): 1644–54.
24. Moschetta A, Modica S, Gadaleta RM. Modulation of nuclear bile acid receptor FXR activity in the gut – liver axis. Nucl Recept Signal 2010; 8: 005.
25. Bedossa P. Current histological classification of NAFLD: strength and limitations. Hepatol Int 2013; 7 (Suppl. 2): S.765–70.
26. Ikura Y. Transitions of histopathologic criteria for diagnosis of nonalcoholic fatty liver disease during the last three decades. World J Hepatol 2014; 12 (6): 894–900.
27. Kleiner DE, Brunt EM, Van Natta M et al. Clinical research network. Design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313–21.
28. InvokanaTM [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; March 2013.
29. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986; 292: 13–5.
30. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatology 2013; 58: 1007–19.
31. Fierbinteanu-Braticevici C, Dina I, Petrisor A et al. Noninvasive investigations for non alcoholic fatty liver disease and liver fibrosis. World J Gastroenterol 2010; 16: 4784–91.
32. Lamos EM, Younk LM, Davis SN. Canagliflozin, an inhibitor of sodium-glucose cotransporter 2, for the treatment of type 2 diabetes mellitus. Exp Opin Drug Metab Toxicol 2013; 9 (6): 763–75.
33. Kleiner DE, Brunt EM, Van Natta M et al. Clinical research network. Design and validation of histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 4: 1313–21.
34. Ratziu V, Bellentani S, Cortez-Pinto H et al. A position statement on NAFLD/NASH based on the EASL 2009 Special Conference. J Hepatol 2010; 53: 372–84.
35. Weyer C, Funahashi T, Tanaka S et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–5.
36. Ratziu V. Current and future insulin sensitizers in the treatment of NASH. EASL 2015, Vienna. http://ilc-congress.eu/pgc/ILC2015-PGC-Book.pdf
37. Trappoliere M, Caligiuri A, Schmid M. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol 2009; 50 (6): 1102–11.
38. Li Y, Liu L, Wang B et al. Metformin in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomed Rep 2013; 1 (1): 57–64.
39. Loomba R, Lutchman G, Kleiner DE et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Alim Pharmacol Ther 2009; 29 (2): 172–82.
40. Haukeland JW, Konopski Z, Eggesbø HB et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 2009; 44 (7): 853–60.
41. Nar A, Gedik O. The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Acta Diabetol 2009; 46 (2): 113–8.
42. Lavine JE, Schwimmer JB, Molleston JP et al. Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemporary Clinical Trials 2010; 31 (1): 62–70.
43. Krakoff J, Clark JM, Crandall JP et al. Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity 2010; 18 (9): 1762–7.
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Авторы
С.В.Родионова1, Л.А.Звенигородская*1, Е.В.Бирюкова2
1 ГБУЗ Московский клинический научный центр Департамента здравоохранения г. Москвы. 111123, Россия, Москва, ш. Энтузиастов, д. 86;
2 ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
*msll@rambler.ru
1 ГБУЗ Московский клинический научный центр Департамента здравоохранения г. Москвы. 111123, Россия, Москва, ш. Энтузиастов, д. 86;
2 ГБОУ ВПО Московский государственный медико-стоматологический университет им. А.И.Евдокимова Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
*msll@rambler.ru
________________________________________________
S.V.Rodionova1, L.A.Zvenigorodskaya*1, E.V.Biryukova2
1 Moscow Clinical Science-Practical Center of the Department of Health of Moscow. 111123, Russian Federation, Moscow, sh. Entuziastov, d. 86;
2 A.I.Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*msll@rambler.ru
1 Moscow Clinical Science-Practical Center of the Department of Health of Moscow. 111123, Russian Federation, Moscow, sh. Entuziastov, d. 86;
2 A.I.Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*msll@rambler.ru
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