Адеметионин в лечении повышенной утомляемости/слабости при заболеваниях печени: систематический обзор
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Raikhelson K.L., Kondrashina E.A. Аdеmethionine in the treatment of fatigue in liver diseases: a systematic review. Therapeutic Archive. 2019; 91 (2): 8–142. DOI: 10.26442/00403660.2019.02.000130
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Цель исследования. Систематизация опубликованных данных по лечению гепатогенной слабости адеметионином.
Материалы и методы. Проведен поиск по базам PubMed, EMBASE, Embase®, Medline®, eLIBRARY.ru работ, опубликованных в 1952–2018 гг.
Результаты и обсуждение. Выявлено 16 работ, посвященных применению адеметионина при заболеваниях печени и оценивающих динамику симптома слабость, среди них одно двойное слепое рандомизированное плацебо-контролируемое исследование, три открытых рандомизированных исследования, большинство работ являлись многоцентровыми открытыми наблюдательными программами. Исследования включали 3238 пациентов (из которых 2820 вошли в окончательный анализ данных) и широкий спектр заболеваний печени: алкогольную болезнь печени, неалкогольную жировую болезнь печени, первичный билиарный холангит, первичный склерозирующий холангит, цирроз печени разного генеза, вирусные гепатиты, лекарственное поражение печени. Использовались различные дозы, пути введения адеметионина и длительность курса.
Заключение. Адеметионин, независимо от пути введения, эффективен в лечении слабости при различных заболеваниях печени, как при краткосрочном, так и при длительном применении. Следует предполагать дозозависимый эффект препарата и возможность сохранения последействия по окончании курса лечения, но это требует дальнейшего изучения в рандомизированных клинических исследованиях.
Ключевые слова: слабость, утомляемость, заболевания печени, лечение, адеметионин, S-аденозилметионин.
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Fatigue has a significant effect on the condition of patients with liver disease. Adеmethionine is considered one of the most promising drugs for its treatment.
Aim. To systematize the published data on the treatment of hepatogenic fatigue with аdеmethionine.
Materials and methods. Search was performed using databases PubMed, EMBASE, Embase®, Medline®, eLIBRARY.ru, published in 1952–2018.
Results and discussion. 16 articles were found on the use of аdеmethionine in liver diseases and the assessment of the dynamics of the symptom of fatigue, including 1 double-blind, randomized, placebo-controlled study, 3 open randomized studies; most of the works were multicenter open observation programs. The studies included 3238 patients (of which 2820 were included in the final data analysis) and a wide range of liver diseases: alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, primary sclerosing cholangitis, cirrhosis of different causes, viral hepatitis, drug-induced liver injury. Different doses, routes of administration of аdеmethionine and the duration of the course were used.
Conclusions. Ademethionine, regardless of the route of administration, is effective in the treatment of fatigue due to different liver disease in the short and long term. The dose-dependent effect of the drug and the possibility of maintaining post-effect after end of the treatment course should be assumed, but this requires further study in randomized clinical trials.
Keywords: fatigue, treatment, liver disease, ademethionine, S-adenosylmethionine.
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3. Newton J, Jones D. Managing systemic symptoms in chronic liver disease. J Hepatol. 2012;56:46-55. doi: 10.1016/s0168-8278(12)60006-3
4. Swain MG, Jones DEJ. Fatigue in chronic liver disease: New insights and therapeutic approaches. Liver Int. 2018. doi: 10.1111/liv [Epub ahead of print]. Accessed 20 October 2018. https://onlinelibrary.wiley.com/doi/full/10.1111/liv.13919
5. Swain MG. Fatigue in liver disease: Pathophysiology and clinical management. Can J Gastroenterol. 2006;20(3):181-8. doi: 10.1155/2006/624832
6. Patidar KR, Bajaj JS. Tired of Hepatitis B? Dig Dis Sci. 2016;61(4):953-4. doi: 10.1007/s10620-016-4067-8
7. Jopson L, Dyson JK, Jones DE. Understanding and Treating Fatigue in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Clin Liver Dis. 2016;20(1):131-42. doi: 10.1016/j.cld.2015.08.007
8. Elliott C, Frith J, Day CP, Jones DE, Newton JL. Functional impairment in alcoholic liver disease and non-alcoholic fatty liver disease is significant and persists over 3 years of follow-up. Dig Dis Sci. 2013;58(8):2383-91. doi: 10.1007/s10620-013-2657-2
9. Chen SS, Yu KK, Huang C, Li N, Zheng JM, Bao SX, Chen MQ, Zhang WH. The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: A retrospective cohort study. Medicine (Baltimore). 2016;95(34):e4683. doi: 10.1097/md.0000000000004683
10. Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, Powell EE. Modest weight loss and physical activity in over-weight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004;53:413-9. doi: 10.1136/gut.2003.027581
11. Melles GF, Pells G, Newton JL, Bathgate AJ, Burroughs AK, Heneghan MA, Neuberger JM, Day DB, Ducker SJ, Sandford RN, Alexander GJ, Jones DE. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58(1):273-83. doi: 10.1002/hep.26365
12. Cauch-Dudek K, Abbey S, Stewart DE, Heathcote EJ. Fatigue in primary biliary cirrhosis. Gut. 1998;43(5):705-10. doi: 10.1136/gut.43.5.705
13. Jones DE. Fatigue in cholestatic liver disease: Is it all in the mind? J Hepatol. 2007;46:992-4. doi: 10.1016/j.jhep.2007.03.006
14. Newton JL, Jones DEJ, Henderson E, Kane L, Wilton K, Burt AD, Day CP. Fatigue in non-alcoholic fatty liver disease is severe and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut. 2008;57:807-13. doi: 10.1136/gut.2007.139303
15. Newton JL. Systemic Symptoms in Non-Alcoholic Fatty Liver Disease. Dig Dis. 2010;28:214-9. doi: 10.1159/000282089
16. Jones DE, Bhala N, Burt J, Goldblatt J, Prince MI, Newton JL. Four year follow up of fatigue in a geographically defined primary biliary cirrhosis patient cohort. Gut. 2006;55(4):536-41. doi: 10.1136/gut.2005.080317
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ФГБОУ ВО «Санкт-Петербургский государственный университет», Санкт-Петербург, Россия
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K.L. Raikhelson, E.A. Kondrashina
Saint-Petersburg State University, Saint Petersburg, Russia