Nichtalkoholische Fettleber bei Kindern und Jugendlichen

J. Jahnel; E. Zöhrer; U. Baumann

doi:10.1055/s-0037-1616304

Kinder- und Jugendmedizin, Table of Contents

Kinder- und Jugendmedizin 2016; 16(01): 56-59
DOI: 10.1055/s-0037-1616304

Gastroenterologie

Schattauer GmbH

Nichtalkoholische Fettleber bei Kindern und Jugendlichen

Pediatric nonalcoholic fatty liver disease

J. Jahnel

¹Medizinische Universität Graz

,

E. Zöhrer

¹Medizinische Universität Graz

,

U. Baumann

²Medizinische Hochschule Hannover

› Author Affiliations

Abstract

Zusammenfassung

Die nichtalkoholische Fettleber ist die häufigste chronische Lebererkrankung im Kindes- und Jugendalter und ist oft mit Adipositas und Diabetes mellitus Typ 2 assoziiert. Der Begriff „Nichtalkoholische Fettleber-Erkrankung“, kurz NAFLD („nonalcoholic fatty liver disease“), beinhaltet ein Erkrankungsspektrum reichend von Fettleber mit fehlender Progression bis hin zur nichtalkoholischen Steatohepatitis (NASH). Bildgebende Verfahren und laborchemische Parameter helfen bei der primären Beurteilung und zur Verlaufsbegutachtung – für die Prognose ausschlagegebend ist die Histologie der Leberbiopsie. Die Therapie von NAFLD beschränkt sich primär auf Änderungen des Lebensstils und der Ernährung, die bariatrische Therapie wird zunehmend angewendet.

Summary

In recent years nonalcoholic fatty liver disease (NAFLD) has become the most prevalent form of chronic liver disease worldwide; it is estimated to afflict 80–90 % of obese and diabetic children. NAFLD in children covers a spectrum from simple steatosis through steatohepatitis (NASH) to progressive hepatic fibrosis, leading to cirrhosis and ultimately hepatic failure at an older age. Assessment of fibrosis and its severity in NAFLD is central for prognosis and therapeutic intervention. Currently, liver biopsy is the most sensitive method to differentiate stages in NAFLD. Diet and exercise have been a focus of treatment for NAFLD and NASH due to the association with obesity and type-2-diabetes.

Schlüsselwörter

Nichtalkoholische Fettleber - Adipositas - Steatosis hepatitis - metabolisches Syndrom

Keywords

Nonalcoholic fatty liver disease - adipositas - steatosis hepatitis - metabolic syndrom

Full Text

References

Literatur
1 WHO. Set of recommendations on the marketing of foods and non – alcoholic beverages to children. 2010
2 Alisi A, Locatelli M, Nobili V. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2010; 13: 397-402.
3 Schwimmer JB, Deutsch R, Rauch JB. et al. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr 2003; 143: 500-505.
4 Manco M, Bedogni G, Marcellini M. et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut 2008; 57: 1283-1287.
5 Ode KL, Frohnert BI, Nathan BM. Identification and treatment of metabolic complications in pediatric obesity. Rev Endocr Metab Disord 2009; 10: 167-188.
6 Nobili V, Pinzani M. Paediatric non-alcoholic fatty liver disease. Gut 2010; 59: 561-564.
7 Jahnel J, Zöhrer E, Alisi A. Serum Bile Acid Levels in Children with NAFLD: A Biomarker for Progression?. J Pediatr Gastroenterol Nutr. 2015
8 Blachier M, Leleu H, Peck-Radosavljevic M. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol 2013; 58: 593-608.
9 Fishbein M, Mogren J, Mogren C. et al. Undetected hepatomegaly in obese children by primary care physicians: a pitfall in the diagnosis of pediatric nonalcoholic fatty liver disease. Clin Pediatr (Phila) 2005; 44: 135-141.
10 Jankowska I, Socha P, Pawlowska J. et al. Recurrence of non-alcoholic steatohepatitis after liver transplantation in a 13-yr-old boy. Pediatr Transplant 2007; 11: 796-798.
11 Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.
12 Hubscher SG. Role of liver biopsy in the assessment of non-alcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2004; 16: 1107-1115.
13 Molleston JP, White F, Teckman J, Fitzgerald JF. Obese children with steatohepatitis can develop cirrhosis in childhood. Am J Gastroenterol 2002; 97: 2460-2462.
14 Schwimmer JB, Behling C, Newbury R. et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-649.
15 Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 434-438.
16 Carter-Kent C, Yerian LM, Brunt EM. et al. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009; 50: 1113-1120.
17 Strauss RS, Barlow SE, Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr 2000; 136: 727-733.
18 Patton HM, Lavine JE, Van Natta ML. et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1961-1971 e2.
19 Manco M, Marcellini M, Devito R. et al. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes (Lond) 2008; 32: 381-387.
20 http://www.kiggs.de
21 Tominaga K, Fujimoto E, Suzuki K. et al. Prevalence of non-alcoholic fatty liver disease in children and relationship to metabolic syndrome, insulin resistance, and waist circumference. Environ Health Prev Med 2009; 14: 142-149.
22 Dongiovanni P, Valenti L, Rametta R. et al. Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease. Gut 2010; 59: 267-273.
23 Savage DB, Tan GD, Acerini CL. et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 2003; 52: 910-917.
24 Bataller R, North KE, Brenner DA. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal. Hepatology 2003; 37: 493-503.
25 Alisi A, Manco M, Devito R. et al. Endotoxin and plasminogen activator inhibitor-1 serum levels associated with nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2010; 50: 645-649.
26 Bataller R, Rombouts K, Altamirano J, Marra F. Fibrosis in alcoholic and nonalcoholic steatohepatitis. Best Pract Res Clin Gastroenterol 2011; 25: 231-244.
27 Fracanzani AL, Valenti L, Bugianesi E. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hep 2008; 48: 792-798.
28 Roberts EA. Steatohepatitis in children. Best Pract Res Clin Gastroenterol 2002; 16: 749-765.
29 Kaechele V, Wabitsch M, Thiere D. et al. Prevalence of Gallbladder Stone Disease in Obese Children and Adolescents: Influence of the Degree of Obesity, Sex, and Pubertal Development. J Pediatr Gastroenterol Nutr 2006; 42: 66-70.
30 Ko JS, Yoon JM, Yang HR. et al. Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci 2009; 54: 2225-2230.
31 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: 700-713.
32 Transaminasenerhöhung bei adipösen Kindern und Jugendlichen. AWMF; 2007 (Accessed 25.10.09, 2009).
33 Baumann U, McKiernan PJ, Kelly DA. The trouble with biopsies. J Pediatr Gastroenterol Nutr 2006; 43: 122.
34 Karsdal MA, Krarup H, Sand JM. Review article: the efficacy of biomarkers in chronic fibroproliferative diseases – early diagnosis and prognosis, with liver fibrosis as an exemplar. Aliment Pharmacol Ther 2014; 40: 233-249.
35 Feldstein AE, Wieckowska A, Lopez AR. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009; 50: 1072-1078.
36 Nobili V, Vizzutti F, Arena U. et al. Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008; 48: 442-448.
37 Bell LN, Theodorakis JL, Vuppalanchi R. et al. Serum proteomics and biomarker discovery across the spectrum of nonalcoholic fatty liver disease. Hepatology 2010; 51: 111-120.
38 Brown R, Dell’Olio D, Evans H. et al. Isolated portal fibrosis and periportal steatosis are features of paediatric NAFLD. Pediatric and Developmental Pathology 2005; 392-423.
39 Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467-2474.
40 Kleiner DE, Brunt EM, Van Natta M. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321.
41 Goldschmidt I, Stieghorst H, Munteanu M. The use of transient elastography and non-invasive serum markers of fibrosis in pediatric liver transplant recipients. Pediatr Transplant. 2013; 17: 525-534.
42 Chalasani N, Younossi Z, Lavine JE. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hep 2012; 55: 2005-2023.
43 Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 21: 871-879.
44 Nadeau KJ, Ehlers LB, Zeitler PS, Love-Osborne K. Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatr Diabetes 2009; 10: 5-13.
45 Vajro P, Mandato C, Franzese A. et al. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr 2004; 38: 48-55.
46 Nobili V, Giorgio V, Liccardo D. Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 2014; 170: 547-553.
47 Lindor KD, Kowdley KV, Heathcote EJ. et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004; 39: 770-778.
48 Inge TH. Bariatric surgery for morbidly obese adolescents: is there a rationale for early intervention?. Growth Horm IGF Res 2006; 16 (Suppl A): S15-19.
49 Nobili V, Vajro P, Dezsofi A. et al. Indications and limitations of bariatric intervention in severely obese children and adolescents with and without nonalcoholic steatohepatitis: ESPGHAN Hepatology Committee Position Statement. J Pediatr Gastroenterol Nutr 2015; 60: 550-561.
50 Roeb E, Steffen HM, Bantel H. et al. S2k Leitlinie für Nicht-alkoholische Fettlebererkrankungen. AWMF Register Nr. 021–025. Januar 2015