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Non-alcoholic fatty liver disease (NAFLD) is deemed to be the leading cause of chronic liver disease in children and adolescents in industrialized countries. NAFLD is associated with abdominal obesity, insulin resistance, carbohydrate intolerance and dyslipidemia; it is relative to metabolic syndrome and is its manifestation. Study data have shown that NAFLD has a higher overall mortality rate and high probability of developing cardiovascular disease, that is not dependent on the presence of classical risk factors of atherosclerosis. The monitoring of the course of the disease over the past 20 years has established a reduction in the duration of survival of patients with NAFLD compared with the expected rate in the general population, the progression of fibrosis in 80 % of cases, the development of decompensated forms of cirrhosis requires the transplantation in 6 % of patients. The tendency to progression of structural changes in the liver with the development of the terminal stages of the disease — cirrhosis and hepatocellular carcinoma, the risk of developing cardiovascular complications, possibility of preventing progredient course in timely therapeutic intervention necessitate early diagnosis of NAFLD in children.
The leading constitutional risk factors of NAFLD that could be modified in the children are obesity and insulin resistance.
The mechanism of NAFLD development and progression is a complex and multifactorial process. Nowadays there are two basic concepts that explain the pathogenesis of NAFLD — «two-hits» theory and «multiple parallel hits» theory.
NAFLD in children has no specific clinical signs and is an accidental finding among asymptomatic patients. The manifestation of the disease occurs mostly over the age of 10 years old. There are nonspecific symptoms in the clinical picture of NAFLD in children — general weakness, rapid fatigability, exhaustion. Usually, the first step in the diagnosis of the disease is detection of elevated hepatic transaminases and/or sonographic signs of steatosis by routine clinical ultrasound.
The diagnosis of NAFLD is possible in the absence of signs of liver injury of another nature, first of all autoimmune and drug-induced hepatitis.
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Brunt E.M. Pathology of nonalcoholic fatty liver disease / E.M Brunt // Rev Gastroenterol Hepatol. — 2010. — Vol. 7. — P. 195-203. Doi: 10.1038/nrgastro.2010.
Nalbantoglu I.L. Role of liver biopsy in nonalcoholic fatty liver disease / I.L. Nalbantoglu, E.M. Brunt // World J. Gastroenterol. — 2014. — Vol. 20, № 27. — P. 9026-9037. Doi: 10.3748/wjg.v20.i27.9026.21.
Von Frerichs F.T. Über den Diabetes / F.T. von Frerichs // Berlin: August Hirschwald, 1884.
Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease / Ludwig J., Viggiano T.R., McGill D.B. [et al.] // Mayo Clin Proc. — 1980. — Vol. 55, № 7. — Р. 434-438.
Steatohepatitis in obese children: a cause of chronic liver dysfunction / Moran J.R., Ghishan F.K., Halter S.A. [et al.] // Am J. Gastroenterol. — 1983. — Vol. 78, № 6. — Р. 374-377.
Non-alcoholic fatty liver disease in children: focus on nutritional interventions / Yang M., Gong S., Ye S.Q. [et al.] // Nutrients. — 2014. — Vol.6, № 11. — Р. 4691-4705. doi: 10.3390/nu6114691.
Kursawe R. Metabolic syndrome in pediatrics / R. Kursawe, N. Santoro // Adv Clin Chem. — 2014. — Vol. 65. — Р. 91-142.
Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk / L. Pacifico, V. Nobili, C. Anania [et al.] // World. J. Gastroenterol. — 2011. — Vol. 17. — P. 3082-3091.
The natural history of non-alcoholic fatty liver disease in children: a follow–up study for up to 20 years / A.E. Feldstein, P. Charatcharoenwitthaya, S. Treeprasertsuk [et al.] // Gut. — 2009. — Vol. 58. — P. 1538-1544.
Obesity and cardiovascular risk in children / B. Shashaj, M.P. Graziani, A.E. Tozzi, M. Manco // Recenti Prog Med. — 2014. — Vol. 105(12). — Р. 454-456. Doi: 10.1701/1706.18614.
Non Alcoholic Fatty Liver. Epidemiology and Natural history / M. Masarone, A. Federico, L. Abenavoli [et al.] // Rev Recent Clin Trials. — 2014. [Epub ahead of print].
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: A systematic analysis for the Global Burden of Disease Study 2013 / Ng M., Fleming T., Robinson M. [et al.] // Lancet. — 2014. — Vol. 384. — Р. 766-781. Doi: 10.1016/S0140-6736(14)60460-8.
Welsh J.A. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010 / J.A. Welsh, S. Karpen, M.B. Vos // J. Pediatr. — 2013. — Vol. 16, № 3. — Р. 496-500. Doi: 10.1016/j.jpeds.2012.08.043.
Поширеність надлишкової маси тіла та підвищеного артеріального тиску серед школярів різних регіонів України / В.Г. Майданник, М.В. Хайтович, Г.А. Павлишин, О.Г. Іванько, Ю.М. Нечитайло, В.В. Очеретько // Международный журнал педиатрии, акушерства и гинекологии. — 2013. — Vol. 3, № 1. — Р. 33-39.
Relation of risk factors between metabolic syndrome and nonalcoholic fatty liver disease in children and adolescents / Smolka V., Ehrmann J.Jr., Tkachyk O. [et al.] // Cas Lek Cesk. — 2014. — Vol. 153, № 2. — Р. 91-97.
Nonalcoholic Fatty Liver Disease: A Challenge for Pediatricians / Nobili V., Alkhouri N., Alisi A. [et al.] // JAMA Pediatr. — 2014. Doi: 10.1001/jamapediatrics.2014.2702.
Heritability of nonalcoholic fatty liver disease / J.B. Schwimmer, M.A. Celedon, J.E. Lavine [et al.] // Gastroenterology. — 2009. — Vol. 136. — P. 1585-1592.
Low birth weight and catch– up– growth associated with metabolic syndrome: a ten year systematic review / V. Nobili, A. Alisi, N. Panera [et al.] // Pediatr. Endocrinol. Rev. — 2008. — № 6. — P. 241-247.
Weight trajectories through infancy and childhood and risk of non-alcoholic fatty liver disease in adolescence: the ALSPAC study / E.L. Anderson, L.D. Howe, A. Fraser [et al.] // J. Hepatol. — 2014. — Vol. 61, № 3. — Р. 626-632. Doi: 10.1016/j.jhep.2014.04.018.
Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population / A. Franzese, P. Vajro, A.Argenziano [et al.] // Dig. Dis. Sci. — 1997. — Vol. 42. — P. 1428-1432.
Prevalence of fatty liver in children and adolescents / J.B. Schwimmer, R. Deutsch, T. Kahen [et al.] // Pediatrics. — 2006. — Vol. 118. — P. 1388-1393.
Obesity,insulin resistance, and other clinicopathologica correlates of pediatric nonalcoholic fatty liver disease / J.B. Schwimmer, R. Deutsch, J.B. Rauch [et al.] // J. Pediatr. — 2003. — Vol. 143. — P. 500-505.
Ethnicity, obesity and the metabolic syndrome: implications on assessing risk and targeting intervention / Deboer M.D. // Expert Rev. Endocrinol. Metab. — 2011. — Vol. 6, № 2. — Р. 279-289.
Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease / M.F. Abdelmalek, A. Suzuki, C. Guy [et al.] // Hepatology. — 2010. — Vol. 51. — P. 1961-1971.
Nonalcoholic fatty liver disease in children / Mencin A.A., Lavine J.E. // Curr. Opin. Clin. Nutr. Metab. Care. — 2011. — Vol. 14, № 2. — Р. 151-157.
Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity / Browning J.D., Szczepa-niak L.S., Dobbins R. [et al.] // Hepatology. — 2004. — Vol. 40. — Р. 1387-1395.
Yu-Yuan Li. Genetic and epigenetic variants influencing the development of nonalcoholic fatty liver disease / Yu-Yuan Li // World J. Gastroenterol. — 2012. — Vol. 18, № 45. — Р. 6546-6551. Doi: 10.3748/wjg.v18.i45.6546.
Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits / Speliotes E.K.,Yerges-Armstrong L.M., Wu J. // PLoS Genet. — 2011. — Vol. 7: e1001324
A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents / Santoro N., Kursawe R, D’Adamo E. [et al.] // Hepato-logy. — 2010. — Vol. 52. — Р. 1281-1290. Doi: 10.1002/hep.23832.
Sookoian S. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease / S. Sookoian, C.J. Pirola // Hepatology. — 2011. — Vol. 53. — P. 1883-1894.
Valenti L. I148M PNPLA3 variant and progressive liver disease: a new paradigm in hepatology / L. Valenti, A. Alisi, V. Nobili // Hepatology. — 2012. — Vol. 56. — P. 1883-1889.
The association between hepatic fat content and liver injury in obese children and adolescents: effects of ethnicity, insulin resistance, and common gene variants / Santoro N., Feldstein A.E., Enoksson E. [et al.] // Diabetes Care. — 2013. — Vol. 36, № 5. — Р. 1353-1360. Doi: 10.2337/dc12-1791.
Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents / Santoro N., Zhang C.K., Zhao H. [et al.] // Hepatology. — 2012. — Vol. 55. — Р. 781-789.
Genetic variants regulating insulin receptor signaling are associated with severity of liver damage in patients with nonalcoholic fatty liver disease / Dongiovanni P., Valenti L., Rametta R. [et al.] // Gut. — 2010. — Vol. 59. — Р. 267-273.
Pediatric fatty liver disease: role of ethnicity and genetics / Marzuillo P., Miraglia del Giudice E., Santoro N. // World J. Gastroenterol. — 2014. — Vol. 20, № 23. — Р. 7347-7355.
Steatohepatitis: a tale of two «hits»? / Day C.P., James O.F. // Gastroenterology. — 1998. — Vol. 114, № 4. — Р. 842-845.
Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis / Tilg H., Moschen A.R. // Hepatology. — 2010. — Vol 52, № 5. — Р. 1836-1846.
Nonalcoholic fatty liver disease: current issues and novel treatment approaches / Lomonaco R., Sunny N.E., Bril F. [et al.] // Drugs. — 2013. — Vol. 73, № 1. — Р. 1-14.
Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis (NASH) / Takaki A., Kawai D., Yamamoto K. // Int J. Mol Sci. — 2014. — Vol. 15, № 5. — Р. 7352-7379. Doi: 10.3390/ijms15057352.
Increased intestinal permeability and tight junction alte-rations in nonalcoholic fatty liver disease / Miele L., Valenza V., La Torre G. [et al.] // Hepatology. — 2009. — Vol. 49, № 6. — Р. 1877-1887.
Meli R. Role of innate immune response in non-alcoholic fatty liver disease: metabolic complications and therapeutic tools / R. Meli, G.M. Raso, A. Calignano // Frontiers Imuno-logy. — 2014. — Vol. 5, № 177. — P. 1-14. Doi: 10.3389/fimmu.2014.00177.
Autophagy and non-alcoholic fatty liver disease / Lavallard V.J., Gual P. // Biomed Res Int. — 2014. Doi: 10.1155/2014/120179.
Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation / Peverill W., Powell L.W., Skoien R. // Int J. Mol Sci. — 2014. — Vol. 15, № 5. — Р.8591-8638. Doi: 10.3390/ijms15058591.
Histopathology of pediatric nonalcoholic fatty liver disease / J.B. Schwimmer, C. Behling, R. Newbury [et al.] // Hepatology. — 2005. — Vol. 42. — P. 641-649.
Acanthosis nigricans in obese Chinese children / Ng H.Y., Young J.H., Huen K.F. [et al.] // Hong Kong Med. J. — 2014. — Vol. 20, № 4. — Р. 290-296. Doi: 10.12809/hkmj134071.
Waist circumference for the screening of the metabolic syndrome in children / L. A. Moreno, I. Pineda, G. Rodréguez [et al.] // Acta Paediatr. — 2002. — Vol. 91. — P. 1307-1312.
McCarthy H.D. The development of waist circumference percentiles in British children aged 5.0–16.9 years / H.D. McCarthy, K.V. Jarrett, H.F. Crawley // Eur. J. Clin. Nutr. — 2001. — Vol. 55. — P. 902-907.
Katzmarzyk P.T. Waist circumference percentiles for Canadian youth 11–18 y of age / P.T. Katzmarzyk // Eur. J. Clin. Nutr. — 2004. — Vol. 58. — P. 1011-1015.
Alanine transferase: An independent indicator of adiposity related comorbidity risk in youth / M. Klein, L. Iazzettii, P. Speiser [et al.] // J. Diabetes. — 2014. Doi: 10.1111/1753-0407.12221.
Targeted hepatic sonography during clinic visits for detection of fatty liver in overweight children: a pilot study / Perito E.R., Tsai P.M., Hawley S. [et al.] // J. Ultrasound Med. — 2013. — Vol. 32, № 4. — P. 637-643.
Berardis S. Pediatric non-alcoholic fatty liver disease: an increasing public health issue / S. Berardis, E. Sokal // Eur. J. Pediatr. — 2014. — Vol. 173(2). — Р. 131-139. Doi: 10.1007/s00431-013-2157-6.
Barlow S. The Expert Committee. Expert committee recommendations on the assessment, prevention, and treatment of child and adolescent overweight and obesity, summary report / S. Barlow // Pediatrics. — 2007. — Vol. 120. — P. S164-S192.
Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion / G.P. August, S. Caprio, I. Fennoy [et al.] // J. Clin. Endocrinol. Metab. — 2008. — Vol. 93. — P. 4576-4599.
Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee / Vajro P., Lenta S., Socha P. // J. Pediatr. Gastroenterol. Nutr. — 2012. — Vol. 54, № 5. — Р. 700-713. Doi: 10.1097/MPG.0b013e318252a13f.