Fettlebererkrankung bei Kindern und Jugendlichen

Zusammenfassung

Die nicht-alkoholbedingte Fettlebererkrankung (NAFL) ist selbst bei Kindern und Jugendlichen eine der häufigsten chronischen Lebererkrankungen in den westlichen Industriestaaten. NAFL ist assoziiert mit Übergewicht, kardiovaskulären Erkrankungen oder Typ-2-Diabetes. Die Kombination von Risikofaktoren, wie z.B. Übergewicht, ungünstige Ernährungsgewohnheiten, Umweltfaktoren und genetische Prädisposition, führt zur Entwicklung einer einfachen Steatose im Kindes- und Jugendalter, die sich im weiteren Verlauf zur Steatohepatitis, Leberfibrose und Zirrhose entwickeln kann. Als wichtigste Voraussetzung, um eine NAFL im Kindes- und Jugendalter festzustellen, muss diese Diagnose überhaupt in Betracht gezogen werden. Erste Hinweise geben dabei erhöhte Alanin-Aminotransferase-Spiegel und eine generalisierte Echogenitätsanhebung in der Leberultraschalluntersuchung. Die histologische Begutachtung einer Leberbiopsie stellt den Goldstandard der NAFL-Diagnostik dar. Die Therapie sollte in Abhängigkeit von weiteren Komorbiditäten des Patienten, wie z.B. Hyperlipidämie oder Insulinresistenz individuell abgestimmt werden, um Spätfolgen im Erwachsenenalter möglichst früh entgegenzuwirken.

Summary

Non-alcoholic fatty liver disease (NALFD) is one of the most common chronic liver diseases in western countries, even in children and adolescents. NAFLD is associated with e.g. overweight, cardiovascular diseases or type 2 diabetes. Risk factors such as overweight, poor eating habits, environmental factors and genetic predisposition lead to simple steatosis in children and adolescents which can further progress to steatohepatitis, fibrosis or cirrhosis. Considering NAFLD as a potential differential diagnosis in children and adolescents is a key in the assessment of pediatric liver disorders. High serum alanineaminotransferase levels and suspect ultrasound scan might be first signs of NAFLD. Histological examination of a liver biopsy is considered the gold standard in the diagnosis of NAFLD. Therapy options should be selected individually and depend on comorbidities such as hyperlipidemia or insulin resistance to avoid long-term effects in adulthood.

Schlüsselwörter

Fettleber - NAFL - Typ-2-Diabetes - Übergewicht - Sleeve-Gastrektomie

Keywords

Fatty liver - NAFLD - children - type 2 diabetes - overweight - sleeve gastrectomy

• Literatur

• 1 Rayfield S, Plugge E. Systematic review and metaanalysis of the association between maternal smoking in pregnancy and childhood overweight and obesity. J Epidemiol Community Health. 2016 Aug 1 [cited 2016 Nov 24]; Avail. from: http://www.ncbi.nlm.nih.gov/pubmed/ 27480843.
• 2 Serdula MK, Ivery D, Coates RJ, Freedman DS, Williamson DF, Byers T. Do obese children become obese adults? A review of the literature. Prev Med (Baltim) 1993; 22 (02) 167-177.
• 3 Byrne CD, Targher G. NAFLD: A multisystem disease. J Hepatol 2015; 62 (01) S47-S64.
• 4 Nobili V, Alkhouri N, Alisi A. et al. Nonalcoholic fatty liver disease: a challenge for pediatricians. JAMA Pediatr 2015; Feb [cited 2016 Oct 25]; 169 (02) 170-176 Available from: http://www.ncbi. nlm.nih.gov/pubmed/25506780.
• 5 Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016; 65 (08) 1038-1048.
• 6 George J, Liddle C. Nonalcoholic Fatty Liver Disease: Pathogenesis and Potential for Nuclear Receptors as Therapeutic Targets. Mol Pharm 2008; 05 (01) 49-59.
• 7 Pessayre D, Fromenty B. NASH: a mitochondrial disease. J Hepatol 2005; 42 (06) 928-940.
• 8 Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer 2014; 14 (09) 581-597.
• 9 Kirpich IA, Marsano LS, McClain CJ. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease. Clin Biochem 2015; 48 (13-14): 923-930.
• 10 Félix DR, Costenaro F, Gottschall CBA, Coral GP. Non-alcoholic fatty liver disease (NAFLD) in obese children - effect of refined carbohydrates in diet. BMC Pediatr 2016; 16 (01) 187.
• 11 Anderson EL, Howe LD, Jones HE. et al. The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and Adolescents: A Systematic Review and Meta-Analysis. PLoS one. 2015 http://dx.doi.org/10.1371/journal. pone.0140908.
• 12 Manco M, Bedogni G, Marcellini M. et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut 2008; 57 (09) 1283-1287.
• 13 Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes 2008; 32 (02) 381-387.
• 14 Deboer MD, Wiener RC, Barnes BH, Gurka MJ. Ethnic differences in the link between insulin re-sistance and elevated ALT. Pediatrics 2013; 132 (03) e718-e726.
• 15 Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 2005; 115 (05) e561-e565.
• 16 Kechagias S, Ernersson A, Dahlqvist O. et al. Fastfood-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008; 57 (05) 649-654.
• 17 Anderson EL, Howe LD, Fraser A, Macdonald-Wallis C, Callaway MP, Sattar N. et al. Childhood energy intake is associated with nonalcoholic fatty liver disease in adolescents. J Nutr 2015; 145 (05) 983-989.
• 18 Oddy WH, Herbison CE, Jacoby P. et al. The Western dietary pattern is prospectively associated with nonalcoholic fatty liver disease in adolescence. Am J Gastroenterol 2013; 108 (05) 778-785.
• 19 Spruss A, Kanuri G, Wagnerberger S. et al. Tolllike receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology 2009; 50 (04) 1094-1104.
• 20 Alisi A, Bedogni G, Baviera G. et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39 (11) 1276-1285.
• 21 Chang W-C, Jia H, Aw W, Saito K, Hasegawa S, Kato H. Beneficial effects of soluble dietary Jerusalem artichoke (Helianthus tuberosus) in the prevention of the onset of type 2 diabetes and non-alcoholic fatty liver disease in high-fructose diet-fed rats. Br J Nutr 2014; 112 (05) 709-717.
• 22 Vos MB, Colvin R, Belt P. et al. Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD. J Pediatr Gastroenterol Nutr 2012; 54 (01) 90-96.
• 23 Martins C, Aires L, Júnior IF. et al. Physical Activity is Related to Fatty Liver Marker in Obese Youth, Independently of Central Obesity or Cardiorespiratory Fitness. J Sports Sci Med 2015; 14 (01) 103-109.
• 24 Anderson EL, Fraser A, Howe LD. et al. Physical Activity Is Prospectively Associated With Adolescent Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr 2016; 62 (01) 110-117.
• 25 Grønbæk H, Lange A, Birkebæk NH. et al. Effect of a 10-week weight loss camp on fatty liver disease and insulin sensitivity in obese Danish children. J Pediatr Gastroenterol Nutr 2012; 54 (02) 223-228.
• 26 Lee S, Bacha F, Hannon T, Kuk JL, Boesch C, Arslanian S. Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial. Diabetes 2012; 61 (11) 2787-2795.
• 27 Molleston P.J, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 2002; 97 (09) 2460-2462.
• 28 Roeb E, Steffen H, Bantel H. et al. S2k-Leitlinie nicht alkoholische Fettlebererkrankungen. Z Gastroenterol 2015; 53 (07) 668-723.
• 29 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 (05) 700-713.
• 30 Wabitsch M, Moß A. Konsensbasierte (S2) Leitlinie zur Diagnostik, Therapie und Prävention von Übergewicht und Adipositas im Kindes-und Jugendalter. Federführend für die AGA. 2013
• 31 Temple JL, Cordero P, Li J, Nguyen V, Oben JA. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence. Int J Mol Sci 2016; 17 (06) 947.
• 32 Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28 (01) 13-24.
• 33 Holterman A, Gurria J, Tanpure S, DiSomma N. Nonalcoholic fatty liver disease and bariatric surgery in adolescents. Semin Pediatr Surg 2014; 23 (01) 49-57.
• 34 Alisi A, Nobili V. Non-alcoholic fatty liver disease in children now: lifestyle changes and pharmacologic treatments. Nutrition 2012; 28 (7-8): 722-726.
• 35 Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010; 52 (01) 79-104.
• 36 Nobili V, Marcellini M, Devito R. et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 2006; 44 (02) 458-465.
• 37 DeVore S, Kohli R, Lake K. et al. A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. J Pediatr Gastroenterol Nutr 2013; 57 (01) 119-123.
• 38 Nobili V, Manco M, Devito R. et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: A randomized, controlled trial. Hepatology 2008; 48 (01) 119-128.
• 39 Navarro-Jarabo JM, Ubiña-Aznar E, Tapia-Ceballos L. et al. Hepatic steatosis and severity-related factors in obese children. J Gastroenterol Hepatol 2013; 28 (09) 1532-1538.