Диагностика и лечение неалкогольной жировой болезни печени: обзор Европейских рекомендаций 2016 года

1. Маев И.В., Андреев Д.Н., Дичева Д.Т., Кузнецова Е.И. Неалкогольная жировая болезнь печени: пособие для врачей. М.: Прима Принт, 2017. / Maev I.V., Andreev D.N., Dicheva D.T., Kuznetsova E.I. Nealkogol'naia zhirovaia bolezn' pecheni: posobie dlia vrachei. M.: Prima Print, 2017. [in Russian]
2. Torres DM, Harrison SA. Nonalcoholic Fatty Liver Disease. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Edited by M Feldman, LS Friedman, LJ Brandt. 10th ed. 2015.
3. Setiawan VW, Stram DO, Porcel J et al. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort. Hepatology 2016; 64 (6): 1969–77.
4. Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (1): 73–84.
5. Ивашкин В.Т., Драпкина О.М., Маев И.В. и др. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в РФ: результаты исследования DIREG 2. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2015; 6: 31–41. / Ivashkin V.T., Drapkina O.M., Maev I.V. i dr. Rasprostranennost' nealkogol'noi zhirovoi bolezni pecheni u patsientov ambulatorno-poliklinicheskoi praktiki v RF: rezul'taty issledovaniia DIREG 2. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2015; 6: 31–41. [in Russian]
6. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents 1998–1994 to 2007–2001. J Pediatr 2013; 162: 496–500.
7. Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol 2016; 22 (36): 8078–93.
8. European Association for the Study of the Liver (EASL). European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64 (6): 1388–402.
9. Маев И.В., Кучерявый Ю.А., Андреев Д.Н. Ожирение и коморбидность: пособие для врачей. М.: Прима Принт, 2016. / Maev I.V., Kucheriavyi Iu.A., Andreev D.N. Ozhirenie i komorbidnost': posobie dlia vrachei. M.: Prima Print, 2016. [in Russian]
10. Маев И.В., Андреев Д.Н. Неалкогольная жировая болезнь печени: механизмы развития, клинические формы и медикаментозная коррекция. Гастроэнтерология (прил. к журн. Consilium Medicum). 2012; 2: 36–9. / Maev I.V., Andreev D.N. Nealkogol'naia zhirovaia bolezn' pecheni: mekhanizmy razvitiia, klinicheskie formy i medikamentoznaia korrektsiia. Gastroenterology (Suppl. Consilium Medicum). 2012; 2: 36–9. [in Russian]
11. Маев И.В., Кузнецова Е.И., Андреев Д.Н., Дичева Д.Т. Современные и перспективные подходы к диагностике неалкогольной жировой болезни печени. Consilium Medicum. 2015; 17 (8): 20–7. / Maev I.V., Kuznetsova E.I., Andreev D.N., Dicheva D.T. Current and future approaches to the diagnosis of non-alcoholic fatty liver disease. Consilium Medicum. 2015; 17 (8): 20–27. [in Russian]
12. Lazo, M, Clark, JM. The epidemiology of nonalcoholic fatty liver disease: A global perspective. Semin Liver Dis 2008; 28: 339–50.
13. Choudhury J, Sanyal AJ. Clinical aspects of fatty liver disease. Semin Liver Dis 2004; 24: 349–62.
14. Маев И.В., Абдурахманов Д.Т., Андреев Д.Н., Дичева Д.Т. Алкогольная болезнь печени. М.: Форте Принт, 2014. / Maev I.V., Abdurakhmanov D.T., Andreev D.N., Dicheva D.T. Alkogol'naia bolezn' pecheni. M.: Forte Print, 2014. [in Russian]
15. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatology 2013; 58: 1007–19.
16. Saadeh S, Younossi ZM, Remer EM et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745–50.
17. Mayo Clinic gastroenterology and hepatology board review. Editor-in-chief SC Hauser; associate editors AS Oxentenko, W Sanchez. 5th edition. 2015.
18. 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.
19. Mazhar SM, Shiehmorteza M, Sirlin CB. Noninvasive assessment of hepatic steatosis. Clin Gastroenterol Hepatol 2009; 7: 135–40.
20. Kotronen A, Peltonen M, Hakkarainen A et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology 2009; 137: 865–72.
21. Lee JH, Kim D, Kim HJ et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 2010; 42 (7): 503–8.
22. Carey E, Carey WD. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete? Cleve Clin J Med 2010;77 (8): 519–27.
23. Dyson JK, Anstee QM, McPherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Front Gastroenterol 2014; 5 (3): 211–8.
24. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol 2008; 7 (4): 350–7.
25. Angulo P, Hui JM, Marchesini G et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45 (4): 846–54.
26. Shah AG, Lydecker A, Murray K et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7 (10): 1104–12.
27. McPherson S, Anstee QM, Henderson E et al. Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol 2013; 25: 652–8.
28. Андреев Д.Н., Дичева Д.Т., Кузнецова Е.И., Маев И.В. Неалкогольная жировая болезнь печени: лечение с позиций доказательной медицины. Лечащий врач. 2017; 2: 12–8. / Andreev D.N., Dicheva D.T., Kuznetsova E.I., Maev I.V. Nealkogol'naia zhirovaia bolezn' pecheni: lechenie s pozitsii dokazatel'noi meditsiny. Lechashchii vrach. 2017; 2: 12–8. [in Russian]
29. Ивашкин В.Т., Маевская М.В., Павлов Ч.С. и др. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2016; 2: 24–42. / Ivashkin V.T., Maevskaia M.V., Pavlov Ch.S. i dr. Klinicheskie rekomendatsii po diagnostike i lecheniiu nealkogol'noi zhirovoi bolezni pecheni Rossiiskogo obshchestva po izucheniiu pecheni i Rossiiskoi gastroenterologicheskoi assotsiatsii. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2016; 2: 24–42. [in Russian]
30. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009; 49: 80–6.
31. Promrat K, Kleiner DE, Niemeier HM et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51: 121–9.
32. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L et al. Weight loss via lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015; 149: 367–78.
33. Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012; 55: 885–904.
34. Glass LM, Dickson RC, Anderson JC et al. Total body weight loss of 10% is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci 2015; 60: 1024–30.
35. Professional Practice Committee for the Standards of Medical Care in Diabetes-2016. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39: S47–S51.
36. Fan JG, Cao HX. Role of diet and nutritional management in nonalcoholic fatty liver disease. J Gastroenterol Hepatol 2013; 28: 81–7.
37. Hannah WN Jr, Harrison SA. Lifestyle and Dietary Interventions in the Management of Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2016; 61(5): 1365–74.
38. Ismail I, Keating SE, Baker MK, Johnson NA. A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat. Obes Rev 2012; 13 (1): 68–91.
39. Houghton D, Thoma C, Hallsworth K et al. Exercise Reduces Liver Lipids and Visceral Adiposity in Patients With Nonalcoholic Steatohepatitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol 2017; 15 (1): 96–102.e3.
40. Sanyal AJ, Chalasani N, Kowdley KV et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis N Engl J Med 2010; 362 (18): 1675–85.
41. Belfort R, Harrison SA, Brown K et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297–307.
42. Ratziu V, Giral P, Jacqueminet S et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008; 135: 100–10.
43. Aithal GP, Thomas JA, Kaye PV et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1176–84.
44. Cusi K, Orsak B, Bril F et al. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial. Ann Intern Med 2016; 165 (5): 305–15.
45. Harrison SA, Torgenson S, Hayashi P et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003; 98: 2485–490.
46. Miller ER 3rd, Pastor-Barriuso R, Dalal D et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37–46.
47. Lippman SM, Klein EA, Goodman PJ et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301: 39–51.
48. Schurks M, Glynn RJ, Rist PM et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 2010; 341: c5702.
49. Xiang Z, Chen YP, Ma KF et al. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol 2013; 13: 140.
50. Marik PE, Varon J. Omega-3 supplements and the risk of cardiovascular events: A systematic review. Clin Card 2009; 32: 365–72.

________________________________________________

1. Maev I.V., Andreev D.N., Dicheva D.T., Kuznetsova E.I. Nealkogol'naia zhirovaia bolezn' pecheni: posobie dlia vrachei. M.: Prima Print, 2017. [in Russian]
2. Torres DM, Harrison SA. Nonalcoholic Fatty Liver Disease. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Edited by M Feldman, LS Friedman, LJ Brandt. 10th ed. 2015.
3. Setiawan VW, Stram DO, Porcel J et al. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort. Hepatology 2016; 64 (6): 1969–77.
4. Younossi ZM, Koenig AB, Abdelatif D et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (1): 73–84.
5. Ivashkin V.T., Drapkina O.M., Maev I.V. i dr. Rasprostranennost' nealkogol'noi zhirovoi bolezni pecheni u patsientov ambulatorno-poliklinicheskoi praktiki v RF: rezul'taty issledovaniia DIREG 2. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2015; 6: 31–41. [in Russian]
6. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents 1998–1994 to 2007–2001. J Pediatr 2013; 162: 496–500.
7. Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol 2016; 22 (36): 8078–93.
8. European Association for the Study of the Liver (EASL). European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64 (6): 1388–402.
9. Maev I.V., Kucheriavyi Iu.A., Andreev D.N. Ozhirenie i komorbidnost': posobie dlia vrachei. M.: Prima Print, 2016. [in Russian]
10. Maev I.V., Andreev D.N. Nealkogol'naia zhirovaia bolezn' pecheni: mekhanizmy razvitiia, klinicheskie formy i medikamentoznaia korrektsiia. Gastroenterology (Suppl. Consilium Medicum). 2012; 2: 36–9. [in Russian]
11. Maev I.V., Kuznetsova E.I., Andreev D.N., Dicheva D.T. Current and future approaches to the diagnosis of non-alcoholic fatty liver disease. Consilium Medicum. 2015; 17 (8): 20–27. [in Russian]
12. Lazo, M, Clark, JM. The epidemiology of nonalcoholic fatty liver disease: A global perspective. Semin Liver Dis 2008; 28: 339–50.
13. Choudhury J, Sanyal AJ. Clinical aspects of fatty liver disease. Semin Liver Dis 2004; 24: 349–62.
14. Maev I.V., Abdurakhmanov D.T., Andreev D.N., Dicheva D.T. Alkogol'naia bolezn' pecheni. M.: Forte Print, 2014. [in Russian]
15. Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatology 2013; 58: 1007–19.
16. Saadeh S, Younossi ZM, Remer EM et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 745–50.
17. Mayo Clinic gastroenterology and hepatology board review. Editor-in-chief SC Hauser; associate editors AS Oxentenko, W Sanchez. 5th edition. 2015.
18. 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.
19. Mazhar SM, Shiehmorteza M, Sirlin CB. Noninvasive assessment of hepatic steatosis. Clin Gastroenterol Hepatol 2009; 7: 135–40.
20. Kotronen A, Peltonen M, Hakkarainen A et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology 2009; 137: 865–72.
21. Lee JH, Kim D, Kim HJ et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 2010; 42 (7): 503–8.
22. Carey E, Carey WD. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete? Cleve Clin J Med 2010;77 (8): 519–27.
23. Dyson JK, Anstee QM, McPherson S. Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging. Front Gastroenterol 2014; 5 (3): 211–8.
24. Loaeza-del-Castillo A, Paz-Pineda F, Oviedo-Cárdenas E et al. AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis. Ann Hepatol 2008; 7 (4): 350–7.
25. Angulo P, Hui JM, Marchesini G et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45 (4): 846–54.
26. Shah AG, Lydecker A, Murray K et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7 (10): 1104–12.
27. McPherson S, Anstee QM, Henderson E et al. Are simple noninvasive scoring systems for fibrosis reliable in patients with NAFLD and normal ALT levels? Eur J Gastroenterol Hepatol 2013; 25: 652–8.
28. Andreev D.N., Dicheva D.T., Kuznetsova E.I., Maev I.V. Nealkogol'naia zhirovaia bolezn' pecheni: lechenie s pozitsii dokazatel'noi meditsiny. Lechashchii vrach. 2017; 2: 12–8. [in Russian]
29. Ivashkin V.T., Maevskaia M.V., Pavlov Ch.S. i dr. Klinicheskie rekomendatsii po diagnostike i lecheniiu nealkogol'noi zhirovoi bolezni pecheni Rossiiskogo obshchestva po izucheniiu pecheni i Rossiiskoi gastroenterologicheskoi assotsiatsii. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2016; 2: 24–42. [in Russian]
30. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009; 49: 80–6.
31. Promrat K, Kleiner DE, Niemeier HM et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51: 121–9.
32. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L et al. Weight loss via lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015; 149: 367–78.
33. Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012; 55: 885–904.
34. Glass LM, Dickson RC, Anderson JC et al. Total body weight loss of 10% is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci 2015; 60: 1024–30.
35. Professional Practice Committee for the Standards of Medical Care in Diabetes-2016. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39: S47–S51.
36. Fan JG, Cao HX. Role of diet and nutritional management in nonalcoholic fatty liver disease. J Gastroenterol Hepatol 2013; 28: 81–7.
37. Hannah WN Jr, Harrison SA. Lifestyle and Dietary Interventions in the Management of Nonalcoholic Fatty Liver Disease. Dig Dis Sci 2016; 61(5): 1365–74.
38. Ismail I, Keating SE, Baker MK, Johnson NA. A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat. Obes Rev 2012; 13 (1): 68–91.
39. Houghton D, Thoma C, Hallsworth K et al. Exercise Reduces Liver Lipids and Visceral Adiposity in Patients With Nonalcoholic Steatohepatitis in a Randomized Controlled Trial. Clin Gastroenterol Hepatol 2017; 15 (1): 96–102.e3.
40. Sanyal AJ, Chalasani N, Kowdley KV et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis N Engl J Med 2010; 362 (18): 1675–85.
41. Belfort R, Harrison SA, Brown K et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297–307.
42. Ratziu V, Giral P, Jacqueminet S et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008; 135: 100–10.
43. Aithal GP, Thomas JA, Kaye PV et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1176–84.
44. Cusi K, Orsak B, Bril F et al. Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial. Ann Intern Med 2016; 165 (5): 305–15.
45. Harrison SA, Torgenson S, Hayashi P et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003; 98: 2485–490.
46. Miller ER 3rd, Pastor-Barriuso R, Dalal D et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37–46.
47. Lippman SM, Klein EA, Goodman PJ et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301: 39–51.
48. Schurks M, Glynn RJ, Rist PM et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 2010; 341: c5702.
49. Xiang Z, Chen YP, Ma KF et al. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol 2013; 13: 140.
50. Marik PE, Varon J. Omega-3 supplements and the risk of cardiovascular events: A systematic review. Clin Card 2009; 32: 365–72.

Д.Н.Андреев*, И.В.Маев, Д.Т.Дичева, Е.И.Кузнецова

ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И.Евдокимова» Минздрава России. 127473, Россия, Москва, ул. Делегатская, д. 20, стр. 1
dna-mit8@mail.ru

________________________________________________

D.N.Andreev*, I.V.Maev, D.T.Dicheva, E.I.Kuznetsova

A.I.Evdokimov Moscow University State of Medicine and Dentistry of the Ministry of Health of the Russian Federation. 127473, Russian Federation, Moscow, ul. Delegatskaia, d. 20, str. 1
*dna-mit8@mail.ru