Стеатогепатиты смешанного генеза: больше вопросов, чем ответов (Часть 1)
- Авторы: Райхельсон К.Л.1, Кондрашина Э.А.1, Пазенко Е.В.1
-
Учреждения:
- Научно-клинический и образовательный центр гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет»
- Выпуск: Том 92, № 12 (2020)
- Страницы: 91-96
- Раздел: Статьи
- URL: https://journals.rcsi.science/0040-3660/article/view/60262
- DOI: https://doi.org/10.26442/00403660.2020.12.200470
- ID: 60262
Цитировать
Полный текст
Аннотация
Термин «стеатогепатит» (СГ) применяется для гетерогенной группы заболеваний различной этиологии, характеризующихся сходной морфологической картиной. Ранее диагноз неалкогольной жировой болезни печени подразумевал исключение других причин СГ, в последние годы предполагается возможность комбинации различных этиологических вариантов СГ. В обзоре рассмотрены терминологические, эпидемиологические и патогенетические аспекты наиболее частого сочетания – метаболического и алкогольного генеза, вопросы взаимного влияния этиопатогенетических факторов и выявления преобладающего процесса. Подробно обсуждаются вопросы существующей и перспективной патогенетической и симптоматической терапии. Основой лечения СГ является устранение известных причинных факторов и модификация образа жизни, в терапии в настоящее время следует использовать препараты, доказавшие эффективность при отдельных вариантах СГ, и симптоматическую терапию.
Полный текст
Открыть статью на сайте журналаОб авторах
Карина Леонидовна Райхельсон
Научно-клинический и образовательный центр гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет»
Автор, ответственный за переписку.
Email: kraikhelson@mail.ru
ORCID iD: 0000-0002-8821-6142
д.м.н., проф.
Россия, Санкт-ПетербургЭлина Александровна Кондрашина
Научно-клинический и образовательный центр гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет»
Email: kraikhelson@mail.ru
ORCID iD: 0000-0002-0142-0264
к.м.н., доц.
Россия, Санкт-ПетербургЕкатерина Владимировна Пазенко
Научно-клинический и образовательный центр гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет»
Email: kraikhelson@mail.ru
ORCID iD: 0000-0002-7590-8932
мл. науч. сотр.
Россия, Санкт-ПетербургСписок литературы
- EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004
- Pimpin L, Cortez-Pinto H, Negro F, et al. Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies. J Hepatol. 2016;69(3):718-35. doi: 10.1016/j.jhep.2018.05.011
- Wandji LCN, Gnemmi V, Mathurin P, Louvet A. Combined alcoholic and non-alcoholic steatohepatitis. JHEP Reports.2020;2(3):100101. doi: 10.1016/j.jhepr.2020.100101
- Francque S, Vonghia L. Pharmacological Treatment for Non-alcoholic Fatty Liver Disease. Adv Ther. 2019;36:1052-74. doi: 10.1007/s12325-019-00898-6
- 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. doi: 10.1002/hep.28431
- Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434-8.
- Powell EE, Cooksley WG, Hanson R, et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 1990;11:74-80.
- Eslam M, Sanya AJ, George J. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158(7):1999-2014. doi: 10.1053/j.gastro.2019.11.312
- Becker U, Deis A, Sorensen TI, et al. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23(5):1025-29. doi: 10.1002/hep.510230513
- Boyle M, Masson S, Anstee QM. The bidirectional impacts of alcohol consumption and the metabolic syndrome: Cofactors for progressive fatty liver disease. J Hepatol. 2018;68(2):251-67. doi: 10.1016/j.jhep.2017.11.006
- Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000;132(2):112-7. doi: 10.7326/0003-4819-132-2-200001180-00004
- Маевская М.В., Бакулин И.Г., Чирков А.А. и др. Злопотребление алкоголем среди пациентов гастроэнтерологического профиля. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2016;26(4):24-35 [Maevskaja MV, Bakulin IG, Chirkov AA, et al. Alcohol abuse among gastroenterological patients. Rus J Gastroenterol Hepatol Coloproctol. 2016;26(4):24-35 (In Russ.)]. doi: 10.22416/1382-4376-2016-26-4-24-35
- Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7(3):e001324. doi: 10.1371/journal.pgen.1001324
- Chamorro AJ, Torres JL, Mirón-Canelo JA, et al. Systematic review with meta-analysis: the I148M variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis. Aliment Pharmacol Ther. 2014;40(6):571-81. doi: 10.1111/apt.12890
- Yang E, Trepo P, Nahon Q, et al. PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases. Int J Cancer. 2019;144(3):533-44. doi: 10.1002/ijc.31910
- Buch S, Stickel F, Trepo E, et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet. 2015;47(12):1443-8. doi: 10.1038/ng.3417
- Nassir F, Rector S, Hammoud GM, Ibdah JA. Pathogenesis and prevention of hepatic steatosis. J Gastroenterol Hepatol. 2015;11(3):167-75.
- Ji C, Chan С, Kaplowitz N. Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murne intragastric ethanol feeding model. J Hepatol. 2006;45(5):717-24. doi: 10.1016/j.jhep.2006.05.009
- Kohjima M, Higuchi N, Kato M, et al. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008;21(4):507-11.
- You M, Matsumoto M, Pacold CM, et al. The role of AMP-activated protein kinase in the action of ethanol in the liver. Gastroenterology. 2004;127(6):1798-808. doi: 10.1053/j.gastro.2004.09.049
- Adolph TE, Grander C, Grabherr F, Tilg H. Adipokines and non-alcoholic fatty liver disease: multiple interactions. Int J Mol Sci. 2017;18(8):1649. doi: 10.3390/ijms18081649
- Tang H, Sebastian BM, Axhemi A, et al. Ethanol-induced oxidative stress via the CYP2E1 pathway disrupts adiponectin secretion from adipocytes. Alcohol Clin Exp Res. 2012;36(2):214-22. doi: 10.1111/j.1530-0277.2011.01607.x
- Greuter T, Gores GJ, Shah VH. Therapeutic opportunities for alcoholic steatohepatitis and nonalcoholic steatohepatitis: exploiting similarities and differences in pathogenesis. JCI Insight. 2017;2(17):e95354. doi: 10.1172/jci.insight.95354
- Bashiardes S, Shapiro H, Rozin S, et al. Molecular Metabolism Non-alcoholic fatty liver and the gut microbiota. Mol Metabol. 2016;5(9):782-94. doi: 10.1016/j.molmet.2016.06.003
- Stärkel P, Leclercq S, de Timary P, Schnabl B. Intestinal dysbiosis and permeability: The yin and yang in alcohol dependence and alcoholic liver disease. Rev Clin Sci. 2018;132(2):199-212. doi: 10.1042/CS20171055
- Rivera CA, Adegboyega P, van Rooijen N, et al. Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. J Hepatol. 2007;47(4):571-79. doi: 10.1016/j.jhep.2007.04.019
- Petrasek J, Csak T, Ganz M, Szabo G. Differences in innate immune signaling between alcoholic and non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2013;28(1):93-8. doi: 10.1111/jgh.12020
- Younossi ZM, Stepanova M, Ong J, et al. Effects of alcohol consumption and metabolic syndrome on mortality in patients with nonalcoholic and alcohol-related fatty liver disease. Clin Gastroenterol Hepatol. 2019;17(8):1625-33. doi: 10.1016/j.cgh.2018.11.033
- Ekstedt M, Franzén LE, Holmqvist M, et al. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2009;44(3):366-74. doi: 10.1080/00365520802555991
- Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: Predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121:91-100. doi: 10.1053/gast.2001.25540
- Dunn W, Sanyal AJ, Brunt EM, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol. 2012;57:384-91. doi: 10.1016/j.jhep.2012.03.024
- Hagstrom H, Nasr P, Ekstedt M, et al. Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2017;52:159-65. doi: 10.1080/00365521.2016.1239759
- Sookoian S, Castaño GO, Pirola CJ. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals. Gut. 2014;63(3):530-2. doi: 10.7717/peerj.2633
- Sookoian S, Flichman D, Castaño GO, Pirola CJ. Mendelian randomisation suggests no beneficial effect of moderate alcohol consumption on the severity of nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2016;44(11-12):1224-34. doi: 10.1111/apt.13828
- Cao G, Tingzhuang Yi, Liu Q, et al. Alcohol consumption and risk of fatty liver disease: a meta-analysis. PeerJ. 2016;4:e2633. doi: 10.7717/peerj.2633
- Ajmera VH, Terrault NA, Harrison SA. Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review. Hepatology. 2017;65(6):2090-9. doi: 10.1002/hep.29055
- Ahmed A, James E. Rohrer Patterns of alcohol drinking and its association with obesity: data from the third national health and nutrition examination survey, 1988–1994. BMC Public Health. 2005;5:126. doi: 10.1186/1471-2458-5-126
- Moriya A, Iwasaki Y, Ohguchi S, et al. Roles of alcohol drinking pattern in fatty liver in Japanese women. Hepatol Int. 2013;7(3):859-68. doi: 10.1016/j.jhep.2014.11.025
- Yamada K, Mizukoshi E, Seike T, et al. Light alcohol consumption has the potential to suppress hepatocellular injury and liver fibrosis in non-alcoholic fatty liver disease. Plos One. 2018;13(1):e0191026. doi: 10.1371/journal.pone.0191026
- Baur A, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337-42. doi: 10.1038/nature05354
- Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. Hepatology. 2008;47(6):1947-54. doi: 10.1002/hep.22292
- Ajmera V, Belt P, Wilson LA, et al. Nonalcoholic Steatohepatitis Clinical Research Network Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is Associated With Less Improvement in Histologic Steatosis and Steatohepatitis. Clin Gastroenterol Hepatol. 2018;16(9):1511-20.e5. doi: 10.1016/j.cgh.2018.01.026
- Mulazzani L, Alvisi M, Goio E, et al. Moderate alcohol consumption is associated with higher gradeof liver fibrosis in patients with non-alcoholic fatty liver disease. Abstract book NAFLD summit 2019. Summit 2019, 26–28 September 2019, Seville, Spain. 2019:94. Accessed September 6, 2020. https://www.easl.eu/nafld2019/wp-content/uploads/2019/09/NAFLD-Summit-2019-Abstract-book.pdf
- Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51(6):1972-8. doi: 10.1002/hep.23527
- Åberg F, Puukka P, Salomaa V, et al. Risks of Light and Moderate Alcohol Use in Fatty Liver Disease: Follow-Up of Population Cohorts. Hepatology. 2020;71(3):835-48. doi: 10.1002/hep.30864
- Loomba CR, Yang HI, Su J, et al. Synergism between obesity and alcohol in increasing the risk of hepatocellular carcinoma: a prospective cohort stud. Am J Epidemiol. 2013;177(4):333-42. doi: 10.1093/aje/kws252
- Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT alcohol consumption questions (AUDIT-C): An effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol use disorders identification test. Arch Intern Med. 1998;158(16):1789-95. doi: 10.1001/archinte.158.16.1789
- Wang J, Li P, Jiang Z, et al. Diagnostic value of alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index combined with γ-glutamyl transferase in differentiating ALD and NAFLD. Korean J Intern Med. 2016;31(3):479-87. doi: 10.3904/kjim.2015.253
- Sorbi D, Boynton J, Lindor KD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating non-alcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol. 1999;94:1018. doi: 10.1111/j.1572-0241.1999.01006.x
- Dunn W, Angulo P, Sanderson S, et al. Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology. 2006;131(4):1057-63. doi: 10.1053/j.gastro.2006.08.020
- Ивашкин В.Т., Маевская М.В., Павлов Ч.С. и др. Клинические рекомендации Российского общества по изучению печени по ведению взрослых пациентов с алкогольной болезнью печени. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2017;27(6):20-40 [Ivashkin VT, Mayevskaya MV, Pavlov ChS, et al. Management of adult patients with alcoholic liver disease: clinical guidelines of the Russian Scientific Liver Society. Rus J Gastroenterol, Hepatol, Coloproctol. 2017;27(6):20-40 (In Russ.)]. doi: 10.22416/1382-4376-2017-27-6-20-40
- Клинические рекомендации: алкогольная болезнь печени у взрослых. Терапия. 2020;4:10-35 [Clinical recommendations: alcoholic liver disease in adult. Therapy. 2020;4:10-35 (In Russ.)]. doi: 10.18565/therapy.2020.4.10–35
- 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
- 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 VT, Maevskaja MV, Pavlov ChS, et al. Clinical guidelines for the diagnosis and treatment of non-alcoholic fatty liver disease of the Russian Society for the Study of the Liver and the Russian Gastroenterological Association. Rus J Gastroenterol Hepatol Coloproctol. 2016;2:24-42 (In Russ.)]. doi: 10.22416/1382-4376-2016-26-2-24-42
- Alkhouri N, Scott A. An update on the pharmacological treatment of nonalcoholic fatty liver disease: beyond lifestyle modifications. Clin Liver Dis. 2018;11(4):82-6. doi: 10.1002/cld.708
- Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367-78. doi: 10.1053/j.gastro.2015.04.005
- Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012;57(1):157-66. doi: 10.1016/j.jhep.2012.02.023
- Kistler KD, Brunt EM, Clark JM, et al. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol. 2011;106(3):460-8. doi: 10.1038/ajg.2010.488
- Gepner Y, Shelef I, Komy O, et al. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. 2019;71(2):379-88. doi: 10.1016/j.jhep.2019.04.013
- Chalasani N, Younossi Z, Lavine JE, e al. Nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases. Hepatology. 2018;67(1):328-57. doi: 10.1002/hep.29367
- Burton R, Sheron N. No level of alcohol consumption improves health. Lancet. 2018;392(10152):987-88. doi: 10.1016/S0140-6736(18)31571-X
- 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
- Liu Y-L, Patman GL, Leathart JBS, et al. Carriage of the PNPLA3 rs738409 polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2017;61:75-81. doi: 10.1016/j.jhep.2014.02.030
- 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. doi: 10.1056/NEJMoa0907929
- Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305:1659-68. doi: 10.1001/jama.2011.520
- Pydyn N, Miękus K, Jura J, Kotlinowski J. New therapeutic strategies in nonalcoholic fatty liver disease: a focus on promising drugs for nonalcoholic steatohepatitis. Pharmacol Rep. 2020;72:1-12. doi: 10.1007/s43440-019-00020-1
- Francque S, Vonghia L. Pharmacological Treatment for Non-alcoholic Fatty Liver Disease. Adv Ther. 2019;36:1052-74. doi: 10.1007/s12325-019-00898-6
- Younossi ZM. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019;394(10215):2184-96. doi: 10.1016/S0140-6736(19)33041-7
- Harrison SA, Goodman Z, Jabbar A, et al. A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis. J Hepatol. 2020;72(5):816-27. doi: 10.1016/j.jhep.2019.11.024
- GENFIT: Announces Results from Interim Analysis of RESOLVE-IT Phase 3 Trial of Elafibranor in Adults with NASH and Fibrosis. May 11, 2020. Accessed September 6, 2020. https://ir.genfit.com/news-releases/news-release-details/genfit-announces-results-interim-analysis-resolve-it-phase-3
- Harrison SA, Wai-Sun Wong V, Okanoue T, et al. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials. J Hepatol. 2020;73(1):26-39. doi: 10.1016/j.jhep.2020.02.027
- 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
- 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;30:1081-9. doi: 10.1016/s0168-8278(99)80263-3
- Elliott C, Frith J, Day CP, et al. 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
- Assimakopoulos K, Karaivazoglou K, Tsermpini EE, et al. Quality of life in patients with nonalcoholic fatty liver disease: A systematic review. J Psychosom Res. 2018;112:73-80. doi: 10.1016/j.jpsychores.2018.07.004
- Райхельсон К.Л., Кондрашина Э.А. Адеметионин в лечении повышенной утомляемости/слабости при заболеваниях печени: систематический обзор. Терапевтический архив. 2019;91(2):134-42 [Raikhelson KL, Kondrashina EA. Ademethionine in the treatment of fatigue in liver diseases: a systematic review. Therapeutic Archive. 2019;91(2):134-42 (In Russ.)]. doi: 10.26442/00403660.2019.02.000130
- Noureddin M, Sander-Struckmeier S, Mato JM. Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. World J Hepatol. 2020;12(2):46-63. doi: 10.4254/wjh.v12.i2.46
- Saigal S, Kapoor D, Roy DS. Ademetionine in patients with liver disease: a review. Int J Res Res Med Sci. 2019;7(6):2482-93: doi: 10.18203/2320-6012.ijrms20192550
- Noureddin M, Mato JM, Lu SC. Nonalcoholic fatty liver disease: Update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp Biol Med (Maywood). 2015;240(6):809-20. doi: 10.1177/1535370215579161
- Mato JM, Martinez-Chantar ML, Shelly CL. S-adenosylmethionine metabolism and liver disease. Ann Hepatol. 2013;12(2):183-9.
- Anstee QM, Day CP. S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J Hepatol. 2012;57(5):1097-109. doi: 10.1016/j.jhep.2012.04.041
- Fiorelli G. S-Adenosylmethionine in the treatment of intrahepatic cholestasis of chronic liver disease: a field trial. Curr Ther Res. 1999;60:335-48. doi: 10.1016/S0011-393X(99)80010-1
- Барановский А.Ю., Райхельсон К.Л., Марченко Н.В. Применение S-аденозилметионина (Гептрала®) в терапии больных неалкогольным стеатогепатитом. Клин. перспективы гастроэнтерологии, гепатологии. 2010;9(1):3-10 [Baranovsky AY, Raykhelson KL, Marchenko NV. S-adenosylmethionine (Heptral®) in treatment of patients with non-alcoholic steatohepatitis. Klin. perspektivy gastroenterologii, gepatologii. 2010;9(1):3-10 (In Russ.)].
- Virukalpattigopalratnam MP, Singh T, Ravishankar AC. Heptral® (Ademetionine) in intrahepatic cholestasis due to chronic non-alcoholic liver disease: subgroup analysis of results of a multicentre observational study in India. J Clin Exp Hepatol. 2014;4(Suppl. 2):S33. doi: 10.1016/j.jceh.2014.02.071
- Boming L. Observation of efficacy of ademetionine for treating non-alcoholic fatty liver disease. Chin J Hepatol. 2011;16(4):350-1.