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Принципы лечения различных форм алкогольной болезни печени
Райхельсон К.Л., Кондрашина Э.А., Пазенко Е.В. Принципы лечения различных форм алкогольной болезни печени. Терапевтический архив. 2023;95(2):187–192. DOI: 10.26442/00403660.2023.02.202071
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
© ООО «КОНСИЛИУМ МЕДИКУМ», 2023 г.
________________________________________________
Raikhelson KL, Kondrashina EA, Pazenko EV. Principles of treatment of different forms of alcoholic liver disease: A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(2):187–192. DOI: 10.26442/00403660.2023.02.202071
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Аннотация
В обзоре рассмотрены принципы лечения различных форм алкогольной болезни печени с точки зрения доказательной базы и клинических рекомендаций. Основной терапией тяжелого алкогольного гепатита являются системные глюкокортикостероиды. Их влияние на выживаемость увеличивается при добавлении антиоксидантов (N-ацетилцистеина, адеметионина). Доказано влияние адеметионина на продолжительность жизни пациентов с алкогольным циррозом классов А и В по Чайлд–Пью. Лечение легких форм алкогольной болезни печени недостаточно разработано, доказательная база у большинства используемых препаратов скромна.
Ключевые слова: алкогольная болезнь печени, алкогольный гепатит, цирроз печени, глюкокортикостероиды, адеметионин, N-ацетилцистеин
Ключевые слова: алкогольная болезнь печени, алкогольный гепатит, цирроз печени, глюкокортикостероиды, адеметионин, N-ацетилцистеин
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The review considers the principles of treatment of various forms of alcoholic liver disease from the point of view of the evidence base and clinical recommendations. The main therapy for severe alcoholic hepatitis is systemic glucocorticosteroids, their effect on survival is increased by the addition of antioxidants (N-acetylcysteine, ademethionine). The effect of ademetionine on the life expectancy of patients with alcoholic cirrhosis of Child–Pugh class A and B has been proven. The treatment of patients with mild forms of alcoholic liver disease is not well developed, and the evidence base for most of the drugs used is modest.
Keywords: alcoholic liver disease, alcoholic hepatitis, liver cirrhosis, glucocorticosteroids, ademetionine, N-acetylcysteine
Полный текст
Список литературы
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5. Rehm J, Shield KD. Global Burden of Alcohol Use Disorders and Alcohol Liver Disease. Biomedicines. 2019;7(4):99. DOI:10.3390/biomedicines7040099
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7. Ritchie H, Roser M. Alcohol Consumption. Our World in Data Published online at OurWorldInData.org. 2018. Available at: https://ourworldindata.org/alcohol-consumption. Accessed: 10.01.2023.
8. Crabb DW, Bataller R, Chalasani NP, et al. Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia. Gastroenterology. 2016;150(4):785-90. DOI:10.1053/j.gastro.2016.02.042
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13. Maddrey WC, Boitnott JK, Bedine MS, et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75:193-9.
14. Louvet A, Naveau S, Abdelnour M, et al. The Lille model a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45(6):1348-54. DOI:10.1002/hep.21607
15. Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619-28. DOI:10.1056/NEJMoa1412278
16. Mathurin P, Mendenhall CL, Carithers RL Jr., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36(4):480-7. DOI:10.1016/s0168-8278(01)00289-6
17. Phillips M, Curtis H, Portmann B, et al. Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis – a randomised clinical trial. J Hepatol. 2006;44(4):784-90. DOI:10.1016/j.jhep.2005.11.039
18. Pavlov CS, Varganova DL, Casazza G, et al. Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev. 2019:4(4):CD001511. DOI:10.1002/14651858.CD001511.pub4
19. Arab JP, Díaz LA, Baeza N, et al. Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study. J Hepatol. 2021;75(5):1026-33. DOI:10.1016/j.jhep.2021.06.019
20. Komkova II, Tkachenko PE, Maevskaya MV, Ivashkin VT. Budesonide in Severe Alcoholic Hepatitis: Results of the Original Research. Am J Clin Med Res. 2016;4(1):7-10. DOI:10.12691/ajcmr-4-1-2
21. Whitfield K, Rambaldi A, Wetterslev J, Gluud C. Pentoxifylline for alcoholic hepatitis. Cochrane Database Syst Rev. 2009;7(4):CD007339. DOI:10.1002/14651858.CD007339.pub2
22. Medina J, Moreno-Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs. 2005;65(17):2445-61. DOI:10.2165/00003495-200565170-00003
23. Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365(19):1781-9. DOI:10.1056/NEJMoa1101214
24. Lavekar A, Deepak S, Aradya V, et al. A Randomised Double-Blind Trial of Pentoxifylline Alone versus Pentoxifylline Plus N Acetyl Cysteine in the Treatment of Severe Alcoholic Hepatitis in a Tertiary Care Hospital in Mysore, Karnataka. J Evid Based Med Healthc. 2021;8(8):399-404. DOI:10.18410/jebmh/2021/78
25. King AL, Mantena SK, Andringa KK, et al. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease. Redox Biol. 2016;9:188-97. DOI:10.1016/j.redox.2016.08.005
26. Lieber CS. S-Adenosyl-L-methionine and alcoholic liver disease in animal models: implications for early intervention in human beings. Alcohol. 2002;27(3):173-7.
DOI:10.1016/s0741-8329(02)00230-6
27. Tkachenko P, Maevskaya M, Pavlov A, et al. Prednisolone plus S-adenosil-L-methionine in severe alcoholic hepatitis. Hepatol Int. 2016;10(6):983-7. DOI:10.1007/s12072-016-9751-4
28. Singh V, Sharma AK, Narasimhan RL, et al. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized pilot study/Virendra Singh et al. Am J Gastroenterol. 2014;109(9):1417-23. DOI:10.1038/ajg.2014.154
29. Simko V, Michael S, Prego V. Ursodeoxycholic therapy in chronic liver disease: a meta-analysis in primary biliary cirrhosis and in chronic hepatitis. Am J Gastroenterol. 1994;89(3):392-8.
30. Евдокимова А.Г., Томова А.В., Терещенко О.И., и др. Клиническая эффективность блокатора бета- и альфа-рецепторов карведилола и орнитина-аспартата у больных ИБС с ХСН в сочетании с алкогольной болезнью печени. Экспериментальная и клиническая гастроэнтерология. 2016;6:42-7 [Evdokimova AG, Tomova AV, Tereshchenko OI, et al. Clinical efficacy of the receptor beta and alpha blockers – carvedilol and ornithine-aspartate in patients with CHD and CHF combined with alcoholic liver disease. Experimental and Clinical Gastroenterology. 2016;6:42-7 (in Russian)].
31. Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand J Gastroenterol. 1989;24(4):407-15. DOI:10.3109/00365528909093067
32. Loguercio C, Nardi G, Argenzio F, et al. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol Alcohol. 1994;29(5):597-604.
33. Le MD, Enbom E, Traum PK, et al. Alcoholic liver disease patients treated with S-adenosyl-L-methionine: an in-depth look at liver morphologic data comparing pre and post treatment liver biopsies. Exp Mol Pathol. 2013;95(2):187-91. DOI:10.1016/j.yexmp.2013.07.003
34. Medici V, Virata MC, Peerson JM, et al. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcohol Clin Exp Res. 2011;35(11):1960-5. DOI:10.1111/j.1530-0277.2011.01547.x
35. Ivashkin VT, Maevskaya MV, Kobalava ZD, et al. Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease. Minerva Gastroenterol Dietol. 2018;64(3):208-19. DOI:10.23736/S1121-421X.18.02461-3
36. Choudhuri G, Singh T. Heptral® (Ademetionine) in patients with chronic alcoholic liver disease: Results of a multicentre observational study in Indian patients. Int J Res Health Sci. 2014;2(3):831-41.
37. Горбаков В.В., Галик В.П., Кириллов С.М. Опыт применения гептрала в лечении диффузных заболеваний печени. Терапевтический архив. 1998;70(10):82-6 [Gorbakov VV, Galik VP, Kirillov SM. Experience in heptral treatment of diffuse liver diseases. Terapevticheskii arkhiv (Ter. Arkh.). 1998;70(10):82-6 (in Russian)].
38. Голованова Е.В. Опыт применения отечественного гепатопротектора Гептор (адеметионин) у больных алкогольной болезнью печени. Фарматека. 2010:12;94-9 [Golovanova EV. Experience in the use of domestic hepatoprotector Heptor (ademetionine) in patients with alcoholic liver disease. Pharmateka. 2010:12;94-9 (in Russian)].
39. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII – Renewing consensus in portal hypertension. J Hepatol. 2021;76(4):959-74. DOI:10.1016/j.jhep.2021.12.022
40. Berzigotti A, Tsochatzis E, Boursier J, et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatology. 2021;75(3):659-89. DOI:10.1016/j.jhep.2021.05.025
41. Mato JM, Cámara J, Fernández de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30(6):1081-9. DOI:10.1016/s0168-8278(99)80263-3
42. Lee TD, Sadda MR, Mendler MH, et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res. 2004;28(1):173-81. DOI:10.1097/01.ALC.0000108654.77178.03
43. Lackner C, Spindelboeck W, Haybaeck J. Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease. Hepatol. 2017;66(3): 610-8. DOI:10.1016/j.jhep.2016.11.011
2. Маев И.В., Абдурахманов Д.Т., Андреев Д.Н., Дичева Д.Т. Алкогольная болезнь печени: современное состояние проблемы. Терапевтический архив. 2014;86(4):108-16 [Maev IV, Abdurakhmanov DT, Andreev DN, Dicheva DT. Alcoholic liver disease: State-of-the-art. Terapevticheskii Arkhiv (Ter. Arkh.). 2014;86(4):108-16 (in Russian)].
3. WHO. Alcohol. Available at: https://www.who.int/news-room/fact-sheets/detail/alcohol. Accessed: 12.12.2022.
4. Mellinger JL. Epidemiology of Alcohol Use and Alcoholic Liver Disease. Clin Liver Dis (Hoboken). 2019;13(5):136-9. DOI:10.1002/cld.806
5. Rehm J, Shield KD. Global Burden of Alcohol Use Disorders and Alcohol Liver Disease. Biomedicines. 2019;7(4):99. DOI:10.3390/biomedicines7040099
6. White AM, Castle IJP, Powell PA, et al. Alcohol-Related Deaths During the COVID-19 Pandemic. JAMA. 2022;327(17):1704-6. DOI:10.1001/jama.2022.4308
7. Ritchie H, Roser M. Alcohol Consumption. Our World in Data Published online at OurWorldInData.org. 2018. Available at: https://ourworldindata.org/alcohol-consumption. Accessed: 10.01.2023.
8. Crabb DW, Bataller R, Chalasani NP, et al. Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia. Gastroenterology. 2016;150(4):785-90. DOI:10.1053/j.gastro.2016.02.042
9. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol. 2018;69(1):154-81. DOI:10.1016/j.jhep.2018.03.018
10. Singal AK, Bataller R, Ahn J, et al. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol. 2018;113(2):175-94. DOI:10.1038/ajg.2017.469
11. Arab JP, Roblero JP, Altamirano J, et al. Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH). Ann Hepatol. 2019;18(3):518-35. DOI:10.1016/j.aohep.2019.04.005
12. Louvet A, Trabut JB, Moreno C, et al. Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines. Liver Int. 2022;42(6):1330-43. DOI:10.1111/liv.15221
13. Maddrey WC, Boitnott JK, Bedine MS, et al. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75:193-9.
14. Louvet A, Naveau S, Abdelnour M, et al. The Lille model a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45(6):1348-54. DOI:10.1002/hep.21607
15. Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619-28. DOI:10.1056/NEJMoa1412278
16. Mathurin P, Mendenhall CL, Carithers RL Jr., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36(4):480-7. DOI:10.1016/s0168-8278(01)00289-6
17. Phillips M, Curtis H, Portmann B, et al. Antioxidants versus corticosteroids in the treatment of severe alcoholic hepatitis – a randomised clinical trial. J Hepatol. 2006;44(4):784-90. DOI:10.1016/j.jhep.2005.11.039
18. Pavlov CS, Varganova DL, Casazza G, et al. Glucocorticosteroids for people with alcoholic hepatitis. Cochrane Database Syst Rev. 2019:4(4):CD001511. DOI:10.1002/14651858.CD001511.pub4
19. Arab JP, Díaz LA, Baeza N, et al. Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study. J Hepatol. 2021;75(5):1026-33. DOI:10.1016/j.jhep.2021.06.019
20. Komkova II, Tkachenko PE, Maevskaya MV, Ivashkin VT. Budesonide in Severe Alcoholic Hepatitis: Results of the Original Research. Am J Clin Med Res. 2016;4(1):7-10. DOI:10.12691/ajcmr-4-1-2
21. Whitfield K, Rambaldi A, Wetterslev J, Gluud C. Pentoxifylline for alcoholic hepatitis. Cochrane Database Syst Rev. 2009;7(4):CD007339. DOI:10.1002/14651858.CD007339.pub2
22. Medina J, Moreno-Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs. 2005;65(17):2445-61. DOI:10.2165/00003495-200565170-00003
23. Nguyen-Khac E, Thevenot T, Piquet MA, et al. Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. N Engl J Med. 2011;365(19):1781-9. DOI:10.1056/NEJMoa1101214
24. Lavekar A, Deepak S, Aradya V, et al. A Randomised Double-Blind Trial of Pentoxifylline Alone versus Pentoxifylline Plus N Acetyl Cysteine in the Treatment of Severe Alcoholic Hepatitis in a Tertiary Care Hospital in Mysore, Karnataka. J Evid Based Med Healthc. 2021;8(8):399-404. DOI:10.18410/jebmh/2021/78
25. King AL, Mantena SK, Andringa KK, et al. The methyl donor S-adenosylmethionine prevents liver hypoxia and dysregulation of mitochondrial bioenergetic function in a rat model of alcohol-induced fatty liver disease. Redox Biol. 2016;9:188-97. DOI:10.1016/j.redox.2016.08.005
26. Lieber CS. S-Adenosyl-L-methionine and alcoholic liver disease in animal models: implications for early intervention in human beings. Alcohol. 2002;27(3):173-7.
DOI:10.1016/s0741-8329(02)00230-6
27. Tkachenko P, Maevskaya M, Pavlov A, et al. Prednisolone plus S-adenosil-L-methionine in severe alcoholic hepatitis. Hepatol Int. 2016;10(6):983-7. DOI:10.1007/s12072-016-9751-4
28. Singh V, Sharma AK, Narasimhan RL, et al. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized pilot study/Virendra Singh et al. Am J Gastroenterol. 2014;109(9):1417-23. DOI:10.1038/ajg.2014.154
29. Simko V, Michael S, Prego V. Ursodeoxycholic therapy in chronic liver disease: a meta-analysis in primary biliary cirrhosis and in chronic hepatitis. Am J Gastroenterol. 1994;89(3):392-8.
30. Евдокимова А.Г., Томова А.В., Терещенко О.И., и др. Клиническая эффективность блокатора бета- и альфа-рецепторов карведилола и орнитина-аспартата у больных ИБС с ХСН в сочетании с алкогольной болезнью печени. Экспериментальная и клиническая гастроэнтерология. 2016;6:42-7 [Evdokimova AG, Tomova AV, Tereshchenko OI, et al. Clinical efficacy of the receptor beta and alpha blockers – carvedilol and ornithine-aspartate in patients with CHD and CHF combined with alcoholic liver disease. Experimental and Clinical Gastroenterology. 2016;6:42-7 (in Russian)].
31. Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand J Gastroenterol. 1989;24(4):407-15. DOI:10.3109/00365528909093067
32. Loguercio C, Nardi G, Argenzio F, et al. Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease. Alcohol Alcohol. 1994;29(5):597-604.
33. Le MD, Enbom E, Traum PK, et al. Alcoholic liver disease patients treated with S-adenosyl-L-methionine: an in-depth look at liver morphologic data comparing pre and post treatment liver biopsies. Exp Mol Pathol. 2013;95(2):187-91. DOI:10.1016/j.yexmp.2013.07.003
34. Medici V, Virata MC, Peerson JM, et al. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcohol Clin Exp Res. 2011;35(11):1960-5. DOI:10.1111/j.1530-0277.2011.01547.x
35. Ivashkin VT, Maevskaya MV, Kobalava ZD, et al. Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease. Minerva Gastroenterol Dietol. 2018;64(3):208-19. DOI:10.23736/S1121-421X.18.02461-3
36. Choudhuri G, Singh T. Heptral® (Ademetionine) in patients with chronic alcoholic liver disease: Results of a multicentre observational study in Indian patients. Int J Res Health Sci. 2014;2(3):831-41.
37. Горбаков В.В., Галик В.П., Кириллов С.М. Опыт применения гептрала в лечении диффузных заболеваний печени. Терапевтический архив. 1998;70(10):82-6 [Gorbakov VV, Galik VP, Kirillov SM. Experience in heptral treatment of diffuse liver diseases. Terapevticheskii arkhiv (Ter. Arkh.). 1998;70(10):82-6 (in Russian)].
38. Голованова Е.В. Опыт применения отечественного гепатопротектора Гептор (адеметионин) у больных алкогольной болезнью печени. Фарматека. 2010:12;94-9 [Golovanova EV. Experience in the use of domestic hepatoprotector Heptor (ademetionine) in patients with alcoholic liver disease. Pharmateka. 2010:12;94-9 (in Russian)].
39. de Franchis R, Bosch J, Garcia-Tsao G, et al. Baveno VII – Renewing consensus in portal hypertension. J Hepatol. 2021;76(4):959-74. DOI:10.1016/j.jhep.2021.12.022
40. Berzigotti A, Tsochatzis E, Boursier J, et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J Hepatology. 2021;75(3):659-89. DOI:10.1016/j.jhep.2021.05.025
41. Mato JM, Cámara J, Fernández de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999;30(6):1081-9. DOI:10.1016/s0168-8278(99)80263-3
42. Lee TD, Sadda MR, Mendler MH, et al. Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res. 2004;28(1):173-81. DOI:10.1097/01.ALC.0000108654.77178.03
43. Lackner C, Spindelboeck W, Haybaeck J. Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease. Hepatol. 2017;66(3): 610-8. DOI:10.1016/j.jhep.2016.11.011
________________________________________________
1. Ministry of Health of the Russian Federation. Alcoholic liver disease (ALD) in adults. Clinical guidelines. Available at: https://cr.minzdrav.gov.ru/recomend/711_1. Accessed: 10.01.2023 (in Russian).
2. Маев И.В., Абдурахманов Д.Т., Андреев Д.Н., Дичева Д.Т. Алкогольная болезнь печени: современное состояние проблемы. Терапевтический архив. 2014;86(4):108-16 [Maev IV, Abdurakhmanov DT, Andreev DN, Dicheva DT. Alcoholic liver disease: State-of-the-art. Terapevticheskii Arkhiv (Ter. Arkh.). 2014;86(4):108-16 (in Russian)].
3. WHO. Alcohol. Available at: https://www.who.int/news-room/fact-sheets/detail/alcohol. Accessed: 12.12.2022.
4. Mellinger JL. Epidemiology of Alcohol Use and Alcoholic Liver Disease. Clin Liver Dis (Hoboken). 2019;13(5):136-9. DOI:10.1002/cld.806
5. Rehm J, Shield KD. Global Burden of Alcohol Use Disorders and Alcohol Liver Disease. Biomedicines. 2019;7(4):99. DOI:10.3390/biomedicines7040099
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Авторы
К.Л. Райхельсон, Э.А. Кондрашина, Е.В. Пазенко*
ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
*kaboi@rambler.ru
ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
*kaboi@rambler.ru
________________________________________________
Karina L. Raikhelson, Elina A. Kondrashina, Ekaterina V. Pazenko*
Saint Petersburg State University, Saint Petersburg, Russia
*kaboi@rambler.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.