vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v20i3/2275vsp-2667Research ArticleОБМЕН ОПЫТОМEXCHANGE OF EXPERIENCEСтеатогепатит у детей с ожирениемSteatohepatitis in Children with Obesityhttps://orcid.org/0000-0002-3896-3297ЗвягинА. А.ZvyaginAlexander A.

Звягин Александр Алексеевич, доктор медицинских наук, профессор кафедры госпитальной и поликлинической педиатрии

394036, Воронеж, ул. Студенческая, д. 10

Voronezh

zvaygaa@mail.ruhttps://orcid.org/0000-0001-6471-8730ФатееваН. Ю.FateevaNatalya Yu.

Воронеж

Voronezh

https://orcid.org/0000-0002-1352-7026ЧубаровТ. В.ChubarovTimofey V.

Воронеж

Voronezh

https://orcid.org/0000-0002-3917-0395ЖдановаО. А.ZhdanovaOlga A.

Воронеж

Voronezh

Воронежский государственный медицинский университет им. Н.Н. БурденкоРоссияBurdenko Voronezh State Medical UniversityRussian FederationВоронежский государственный медицинский университет им. Н.Н. БурденкоРоссияN.N. Burdenko Voronezh State Medical UniversityRussian Federation202114072021203238244Copyright © Звягин А.А., Фатеева Н.Ю., Чубаров Т.В., Жданова О.А., 20212021Звягин А.А., Фатеева Н.Ю., Чубаров Т.В., Жданова О.А.Zvyagin A.A., Fateeva N.Y., Chubarov T.V., Zhdanova O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/2667

В статье обсуждаются вопросы развития, диагностики и терапии стеатогепатита у детей. Стеатогепатит является одной из форм неалкогольной жировой болезни печени, диагностируемой у 12–26% детей с ожирением. В числе патогенетических факторов определены оксидативный стресс, генетическая предрасположенность, нарушения микробиоты, дефицит витамина D. Приведены сведения по алгоритму диагностики в соответствии с рекомендациями Евро пейского и Северо-Американского обществ детских гастроэнтерологов, гепатологов и нутрициологов. Дана характеристика инструментальным методам диагностики стеатогепатита (биопсия, ультразвук, магнитно-резонансная и компьютерная томография, эластография, биохимические тесты), определены показания для их применения в детском возрасте. Приводятся данные по лечению стеатогепатита, которое включает диету и физическую активность, а также обсуждаются возможности применения у детей гепатопротекторов (урсодезоксихолевой кислоты, эссенциальных фосфолипидов) и биологически активных веществ. 

The article discusses the issues of steatohepatitis development, diagnosis, and management in children. Steatohepatitis is one of the forms of non-alcoholic fatty liver disease diagnosed in 12–26% of children with obesity. The major pathogenetic factors are the following: oxidative stress, genetic predisposition, microbiota disorders, vitamin D deficiency. The information on the diagnostic algorithm is presented in accordance with the guidelines of the European and North American Societies of Pediatric Gastroenterologists, Hepatologists and Nutritionists. The characteristics of instrumental methods of steatohepatitis diagnostics (biopsy, ultrasound, magnetic resonance and computed tomography, elastography, biochemical tests) are given, as well as indications for their use in children are determined. The data on steatohepatitis management (including diet and physical activity) is presented. The use of hepatoprotective agents (ursodeoxycholic acid, essential phospholipids) and biologically active substances in children is discussed. 

стеатогепатитнеалкогольная жировая болезнь печенидетиожирениедиагностикалечениеsteatohepatitisnon-alcoholic fatty liver diseasechildrenobesitydiagnosismanagementНе указанNot specifiedReferencesVos MB, Abrams SH, Barlow SE, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64(2):319–334. doi: 10.1097/MPG.0000000000001482Vos MB, Abrams SH, Barlow SE, et al. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017;64(2):319–334. doi: 10.1097/MPG.0000000000001482Sahota AK, Shapiro WL, Newton KP, et al. Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009–2018. Pediatrics. 2020;146(6):e20200771. doi: 10.1542/peds.2020-0771Sahota AK, Shapiro WL, Newton KP, et al. Incidence of Nonalcoholic Fatty Liver Disease in Children: 2009–2018. Pediatrics. 2020;146(6):e20200771. doi: 10.1542/peds.2020-0771Рекомендации по диагностике, лечению и профилактике ожирения у детей и подростков. — М.: Практика; 2015. — С. 19.Rekomendatsii po diagnostike, lecheniyu i profilaktike ozhireniya u detei i podrostkov. Moscow: Praktika; 2015. p. 19. (In Russ).Vajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54(5):700–713. doi: 10.1097/MPG.0b013e318252a13fVajro P, Lenta S, Socha P, et al. Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2012;54(5):700–713. doi: 10.1097/MPG.0b013e318252a13fRito AI, Buoncristiano M, Spinelli A, et al. Association between Characteristics at Birth, Breastfeeding and Obesity in 22 Countries: The WHO European Childhood Obesity Surveillance Initiative — COSI 2015/2017. Obes Facts. 2019;12(2):226–243. doi: 10.1159/000500425Rito AI, Buoncristiano M, Spinelli A, et al. Association between Characteristics at Birth, Breastfeeding and Obesity in 22 Countries: The WHO European Childhood Obesity Surveillance Initiative — COSI 2015/2017. Obes Facts. 2019;12(2):226–243. doi: 10.1159/000500425Намазова-Баранова Л.С., Елецкая К.А., Кайтукова Е.В., Макарова С.Г. Оценка физического развития детей среднего и старшего школьного возраста: анализ результатов одномоментного исследования // Педиатрическая фармакология. — 2018. — Т. 15. — № 4. — С. 333–342. doi: 10.15690/pf.v15i4.1948Namazova-Baranova LS, Yeletskaya KA, K aytukova EV, Маkarova SG. Evaluation of the Physical Development of Children of Secondary School Age: an Analysis of the Results of a Cross-Sectional Study. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2018;15(4):333–342. (In Russ). doi: 10.15690/pf.v15i4.1948Mapping the health system response to childhood obesity in the WHO European Region. An overview and country perspectives. Copenhagen: World Health Organization Regional Office for Europe; 2019. 4 p. Available online: https://www.euro.who.int/__data/assets/pdf_file/0019/401176/Childhood-obesity-web.pdf. Accessed on June 23, 2021.Mapping the health system response to childhood obesity in the WHO European Region. An overview and country perspectives. Copenhagen: World Health Organization Regional Office for Europe; 2019. 4 p. Available online: https://www.euro.who.int/__data/assets/pdf_file/0019/401176/Childhood-obesity-web.pdf. Accessed on June 23, 2021.Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017;15(1):45. doi: 10.1186/s12916-017-0806-8Neuschwander-Tetri BA. Non-alcoholic fatty liver disease. BMC Med. 2017;15(1):45. doi: 10.1186/s12916-017-0806-8Ling JR, Zhang YJ, Zhang ZH, et. al. Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease. Zhonghua Er Ke Za Zhi. 2018;56(11):850–855. doi: 10.3760/cma.j.issn.0578-1310.2018.11.011Ling JR, Zhang YJ, Zhang ZH, et. al. Specific changes of intestinal microflora in children with nonalcoholic fatty liver disease. Zhonghua Er Ke Za Zhi. 2018;56(11):850–855. doi: 10.3760/cma.j.issn.0578-1310.2018.11.011Yang F, Dai Y, Min C, Li X. Neonatal overfeeding induced glucocorticoid overexposure accelerates hepatic lipogenesis in male rats. Nutr Metab (Lond). 2018;15:30 doi: 10.1186/s12986-018-0272-0Yang F, Dai Y, Min C, Li X. Neonatal overfeeding induced glucocorticoid overexposure accelerates hepatic lipogenesis in male rats. Nutr Metab (Lond). 2018;15:30 doi: 10.1186/s12986-018-0272-0Flisiak-Jackiewicz M, Lebensztejn DM. Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children. Clin Exp Hepatol. 2019;5(1):11–21. doi: 10.5114/ceh.2019.83152Flisiak-Jackiewicz M, Lebensztejn DM. Update on pathogenesis, diagnostics and therapy of nonalcoholic fatty liver disease in children. Clin Exp Hepatol. 2019;5(1):11–21. doi: 10.5114/ceh.2019.83152Богомолов П.О., Кокина К.Ю., Майоров А.Ю., Мишина Е.Е. Генетические аспекты неалкогольной жировой болезни печени // Вопросы современной педиатрии. — 2018. — Т. 17. — № 6. — С. 442–448. doi: 10.15690/vsp.v17i6.1974Bogomolov PO, Kokina KYu, Mayorov AYu, Mishina EE. Genetic Aspects of Non-Alcoholic Fatty Liver Disease. Voprosy sovremennoi pediatrii — Current Pediatrics. 2018;17(6):442–448. (In Russ). doi: 10.15690/vsp.v17i6.1974Nikolaou N, Gathercole L, Marchand L, et al. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease. Metabolism. 2019;99:67–80. doi: 10.1016/j.metabol.2019.153947Nikolaou N, Gathercole L, Marchand L, et al. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease. Metabolism. 2019;99:67–80. doi: 10.1016/j.metabol.2019.153947Wang X, Zhou Y, Zhang M, et al. The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China. Genes Dis. 2018;6(1):88–95. doi: 10.1016/j.gendis.2018.07.003Wang X, Zhou Y, Zhang M, et al. The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing, China. Genes Dis. 2018;6(1):88–95. doi: 10.1016/j.gendis.2018.07.003Kong M, Longdong Zhu, Bai L, et al. Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model. Am J Physiol Gastrointest Liver Physiol. 2014;307(9):G883–G893. doi: 10.1152/ajpgi.00427.2013Kong M, Longdong Zhu, Bai L, et al. Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model. Am J Physiol Gastrointest Liver Physiol. 2014;307(9):G883–G893. doi: 10.1152/ajpgi.00427.2013Cimini FA, Barchetta I, Carotti S, et al. Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease. World J Gastroenterol. 2017;23(19):3407–3417. doi: 10.3748/wjg.v23.i19.3407Cimini FA, Barchetta I, Carotti S, et al. Relationship between adipose tissue dysfunction, vitamin D deficiency and the pathogenesis of non-alcoholic fatty liver disease. World J Gastroenterol. 2017;23(19):3407–3417. doi: 10.3748/wjg.v23.i19.3407Yodoshi, T, Orkin S, Arce-Clachar AC, et al. Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease. Eur J Clin Nutr. 2020;74(3): 427–435. doi: 10.1038/s41430-019-0493-yYodoshi, T, Orkin S, Arce-Clachar AC, et al. Vitamin D deficiency: prevalence and association with liver disease severity in pediatric nonalcoholic fatty liver disease. Eur J Clin Nutr. 2020;74(3): 427–435. doi: 10.1038/s41430-019-0493-ySchwimmer JB, Newton KP, Awai HI, et al. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38(10):1267–1277. doi: 10.1111/apt.12518Schwimmer JB, Newton KP, Awai HI, et al. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013;38(10):1267–1277. doi: 10.1111/apt.12518Chen J, Chen J, Fu H, et al. Hypoxia exacerbates non-alcoholic fatty liver disease via HIF-2α/PPARα pathway. Am J Physiol Endocrinol Metab. 2019;317(4):E710–E722. doi: 10.1152/ajpendo.00052.2019Chen J, Chen J, Fu H, et al. Hypoxia exacerbates non-alcoholic fatty liver disease via HIF-2α/PPARα pathway. Am J Physiol Endocrinol Metab. 2019;317(4):E710–E722. doi: 10.1152/ajpendo.00052.2019Elkabany ZA, Hamza RT, Ismail EAR, et al. Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: relation to transient elastography with controlled attenuation parameter. Eur J Gastroenterol Hepatol. 2020;32(8):1008–1016. doi: 10.1097/MEG.0000000000001608Elkabany ZA, Hamza RT, Ismail EAR, et al. Serum visfatin level as a noninvasive marker for nonalcoholic fatty liver disease in children and adolescents with obesity: relation to transient elastography with controlled attenuation parameter. Eur J Gastroenterol Hepatol. 2020;32(8):1008–1016. doi: 10.1097/MEG.0000000000001608Wen H, Wang HJ, Dong B, Ma J. Relationship between serum visfatin level and children and adolescent obesity and non-alcoholic fatty liver disease. Zhonghua Liu Xing Bing Xue Za Zhi. 2012;33(3):269–272.Wen H, Wang HJ, Dong B, Ma J. Relationship between serum visfatin level and children and adolescent obesity and non-alcoholic fatty liver disease. Zhonghua Liu Xing Bing Xue Za Zhi. 2012;33(3):269–272.Cura-Esquivel I, Cordero-Pérez P, Torres-González L, Muñoz-Espinosa LE. Acute phase markers in obese children and adolescents with metabolic disorders. Arch Argent Pediatr. 2018;116(4): 275–282. doi: 10.5546/aap.2018.eng.275Cura-Esquivel I, Cordero-Pérez P, Torres-González L, Muñoz-Espinosa LE. Acute phase markers in obese children and adolescents with metabolic disorders. Arch Argent Pediatr. 2018;116(4): 275–282. doi: 10.5546/aap.2018.eng.275Hua M, Huang J-L, Hu C-C, et al. Including Fibroblast Growth Factor-21 in Combined Biomarker Panels Improves Predictions of Liver Steatosis Severity in Children. Front Pediatr. 2019;7:420. doi: 10.3389/fped.2019.00420Hua M, Huang J-L, Hu C-C, et al. Including Fibroblast Growth Factor-21 in Combined Biomarker Panels Improves Predictions of Liver Steatosis Severity in Children. Front Pediatr. 2019;7:420. doi: 10.3389/fped.2019.00420Aksoy GK, Artan R, Aksoy C, et al. Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in Children. Pediatr Gastroenterol Hepatol Nutr. 2019;22(5):470–478. doi: 10.5223/pghn.2019.22.5.470Aksoy GK, Artan R, Aksoy C, et al. Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in Children. Pediatr Gastroenterol Hepatol Nutr. 2019;22(5):470–478. doi: 10.5223/pghn.2019.22.5.470Mann JP, Raponi M, Nobili V. Clinical implications of understanding the association between oxidative stress and pediatric NAFLD. Expert Rev Gastroenterol Hepatol. 2017;11(4):371–382. doi: 10.1080/17474124.2017.1291340Mann JP, Raponi M, Nobili V. Clinical implications of understanding the association between oxidative stress and pediatric NAFLD. Expert Rev Gastroenterol Hepatol. 2017;11(4):371–382. doi: 10.1080/17474124.2017.1291340Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: cytokine–adipokine interplay and regulation of insulin resistance. Gastroenterology. 2006;131(3):934–945. doi: 10.1053/j.gastro.2006.05.054Tilg H, Hotamisligil GS. Nonalcoholic fatty liver disease: cytokine–adipokine interplay and regulation of insulin resistance. Gastroenterology. 2006;131(3):934–945. doi: 10.1053/j.gastro.2006.05.054Ballestri S, Lonardo A, Romagnoli D, et al. Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver Int. 2012;32(8): 1242–1252. doi: 10.1111/j.1478-3231.2012.02804.xBallestri S, Lonardo A, Romagnoli D, et al. Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver Int. 2012;32(8): 1242–1252. doi: 10.1111/j.1478-3231.2012.02804.xLiu H, Yang MC, Su YT, et al. Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease. Front Pediatr. 2019;6:416. doi: 10.3389/fped.2018.00416Liu H, Yang MC, Su YT, et al. Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease. Front Pediatr. 2019;6:416. doi: 10.3389/fped.2018.00416Kwon YD, Ko KO, Lim JW, et al. Usefulness of Transient Elastography for Non-Invasive Diagnosis of Liver Fibrosis in Pediatric Non-Alcoholic Steatohepatitis. J Korean Med Sci. 2019;34(23):e165. doi: 10.3346/jkms.2019.34.e165Kwon YD, Ko KO, Lim JW, et al. Usefulness of Transient Elastography for Non-Invasive Diagnosis of Liver Fibrosis in Pediatric Non-Alcoholic Steatohepatitis. J Korean Med Sci. 2019;34(23):e165. doi: 10.3346/jkms.2019.34.e165Bedossa P. Current histological classification of NAFLD: strength and limitations. Hepatol Int. 2013;7(2):765–770. doi: 10.1007/s12072-013-9446-zBedossa P. Current histological classification of NAFLD: strength and limitations. Hepatol Int. 2013;7(2):765–770. doi: 10.1007/s12072-013-9446-zPoynard T, Lassailly G, Diaz E, et al. Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data. PLoS One. 2012;7(3):e30325. doi: 10.1371/journal.pone.0030325Poynard T, Lassailly G, Diaz E, et al. Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data. PLoS One. 2012;7(3):e30325. doi: 10.1371/journal.pone.0030325Lin HZ, Yang SQ, Chuckaree C, et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med. 2000;6(9): 998–1003. doi: 10.1038/79697Lin HZ, Yang SQ, Chuckaree C, et al. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med. 2000;6(9): 998–1003. doi: 10.1038/79697Bugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100(5):1082–1090. doi: 10.1111/j.1572-0241.2005.41583.xBugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100(5):1082–1090. doi: 10.1111/j.1572-0241.2005.41583.xLavine 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(16):1659–1668. doi: 10.1001/jama.2011.520Lavine 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(16):1659–1668. doi: 10.1001/jama.2011.520Ratziu V, de Ledinghen V, Oberti F, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54(5):1011–1019. doi: 10.1016/j.jhep.2010.08.030Ratziu V, de Ledinghen V, Oberti F, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol. 2011;54(5):1011–1019. doi: 10.1016/j.jhep.2010.08.030Рейзис А.Р. Неалкогольная жировая болезнь печени в свете проблемы гепатитов невыясненной этиологии у детей и подростков // РМЖ. — 2019. — № 7. — С. 26–29.Reyzis AR. Non-alcoholic fatty liver disease — a new view of the hepatitis problem of unknown etiology in children and adolescents. RMJ. 2019;(7):26–29. (In Russ).Dufour JF, Oneta CM, Gonvers JJ, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12): 1537–1543. doi: 10.1016/j.cgh.2006.09.025Dufour JF, Oneta CM, Gonvers JJ, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006;4(12): 1537–1543. doi: 10.1016/j.cgh.2006.09.025Казюлин А.Н. Место урсодезоксихолевой кислоты в терапии неалкогольной жировой болезни печени на разных стадиях заболевания: стеатоз, стеатогепатит, фиброз/цирроз // РМЖ. — 2017. — № 17. — С. 1248–1257.Kazyulin AN. Place of ursodeoxycholic acid in the therapy of non-alcoholic fatty liver disease at different stages: steatosis, steatohepatitis, fibrosis/ cirrhosis. RMJ. 2017;(17):1248–1257. (In Russ).Caro-Sabido EA, Larrosa-Haro A. Efficacy of dietary intervention and physical activity in children and adolescents with nonalcoholic fatty liver disease associated with obesity: A scoping review. Rev Gastroenterol Mex. 2019;84(2):185–194. doi: 10.1016/j.rgmx.2019.02.001Caro-Sabido EA, Larrosa-Haro A. Efficacy of dietary intervention and physical activity in children and adolescents with nonalcoholic fatty liver disease associated with obesity: A scoping review. Rev Gastroenterol Mex. 2019;84(2):185–194. doi: 10.1016/j.rgmx.2019.02.001Pervez MA, Khan DA, Ijaz A, Khan S. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol. 2018;29(2):170–176. doi: 10.5152/tjg.2018.17297Pervez MA, Khan DA, Ijaz A, Khan S. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease. Turk J Gastroenterol. 2018;29(2):170–176. doi: 10.5152/tjg.2018.17297Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52(6):740–743. doi: 10.1097/MPG.0b013e31821f9b85Vajro P, Mandato C, Licenziati MR, et al. Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease. J Pediatr Gastroenterol Nutr. 2011;52(6):740–743. doi: 10.1097/MPG.0b013e31821f9b85Eslamparast T, Poustchi H, Zamani F, et al. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr. 2014; 99(3):535–542. doi: 10.3945/ajcn.113.068890Eslamparast T, Poustchi H, Zamani F, et al. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Am J Clin Nutr. 2014; 99(3):535–542. doi: 10.3945/ajcn.113.068890Павловская Е.В., Строкова Т.В., Багаева М.Э. и др. Эффективность пробиотиков в лечении неалкогольной жировой болезни печени у детей с ожирением // РМЖ. — 2020. — № 2. — С. 7–10.Pavlovskaya EV, Strokova TV, Bagaieva ME, et al. Probiotics efficacy in the treatment of non-alcoholic fatty liver disease in children with obesity. RMJ. 2020;(2):7–10. (In Russ).Spahis S, Alvarez F, Ahmed N, Dubois J, et al. Non-alcoholic fatty liver disease severity and metabolic complications in obese children: impact of omega-3 fatty acids. J Nutr Biochem. 2018;58:28–36. doi: 10.1016/j.jnutbio.2018.03.025Spahis S, Alvarez F, Ahmed N, Dubois J, et al. Non-alcoholic fatty liver disease severity and metabolic complications in obese children: impact of omega-3 fatty acids. J Nutr Biochem. 2018;58:28–36. doi: 10.1016/j.jnutbio.2018.03.025

The authors declare that there are no conflicts of interest present.