Download PDF
Adipositas - Ursachen, Folgeerkrankungen, Therapie 2010; 04(02): 70-78
DOI: 10.1055/s-0037-1618699
NAFLD/NASH bei Adipositas
Schattauer GmbH

Die nichtalkoholische Fettlebererkrankung (NAFLD) bei Kindern und Jugendlichen

Non-alcoholic fatty liver disease (NAFLD) in children and adolescents
C. Denzer
1   Sektion Pädiatrische Endokrinologie und Diabetologie, Interdisziplinäre Adipositasambulanz, Universitätsklinik für Kinder- und Jugendmedizin, Ulm
,
M. Wabitsch
1   Sektion Pädiatrische Endokrinologie und Diabetologie, Interdisziplinäre Adipositasambulanz, Universitätsklinik für Kinder- und Jugendmedizin, Ulm
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die nichtalkoholische Fettlebererkrankung (NAFLD) ist heute die häufigste Lebererkrankung bei Kindern und Jugendlichen in den industrialisierten Ländern. In Deutschland sind nach vorliegenden Untersuchungen ca. 30 Prozent der adipösen Kinder und Jugendlichen von einer NAFLD betroffen. Das Spektrum der NAFLD bei Kindern und Jugendlichen reicht von der einfachen Leberverfettung (Steatosis hepatis), über die Fettleberentzündung (Steatohepatitis) bis hin zu Fibrose und Zirrhose, d. h. Funktionsverlust des Lebergewebes. Alter, Geschlecht, Ethnizität, Insulin - resistenz und Sexualhormone sind wichtige Faktoren in der Pathogenese einer NAFLD bei Kindern und Jugendlichen. Die NAFLD ist zudem bereits im Kindes- und Jugendalter mit erheblicher, frühmanifester kardiovaskulärer Komorbidität assoziiert. Die vorliegende Literaturübersicht fasst aktuelle Daten zur Epidemiologie, Pathophysiologie, Komorbidität und Therapie der NAFLD im Kindes- und Jugendalter zusammen.

Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents in industrialized countries. Recent studies demonstrate a prevalence rate of NAFLD in overweight and obese children and adolescents in Germany of up to 30 %. The spectrum of NAFLD ranges from pure fatty infiltration (steatosis) to inflammation (steatohepatitis, also known as NASH) to fibrosis and even cirrhosis, which consequently means loss of function of liver tissue. Age, gender, ethnicity, insulin resistance, and sex steroids are implicated in the pathogenesis NAFLD in childhood and adolescence. Moreover, NAFLD in the pediatric age group is associated with marked cardiovascular comorbidities. This review focuses on current data regarding empidemiology, pathophysiology, comorbidities, and treatment of NAFLD in children and adolescents.

Schlüsselwörter

Nichtalkoholische Fettlebererkrankung - Steatohepatitis - Adipositas im Kindes- und Jugendalter - Insulinresistenz - viszerales Fettgewebe

Keywords

Non-alcoholic fatty liver disease - non-alcoholic steatohepatitis - childhood obesity - insulin resistance - visceral adipose tissue
 

  • Literatur

  • 1 Baldridge AD, Perez-Atayde AR, Graeme-Cook F. et al. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J Pediatr 1995; 127: 700-704.
    CrossrefPubMedGoogle Scholar
  • 2 Baumann U, Keller KM, Koletzko S. et al. Transaminasenerhöhung bei Kindern und Jugendliche. Leitlinie der Gesellschaft für Pädiatrische Gastroenterologie und Ernährung (GPGE). AWMF-Leitlinien-Register. 2007 Nr. 068/022.
    PubMedGoogle Scholar
  • 3 Bottner A, Kratzsch J, Muller G. et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004; 89: 4053-4061.
    CrossrefPubMedGoogle Scholar
  • 4 Bugianesi E, Pagotto U, Manini R. et al. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity. J Clin Endocrinol Metab 2005; 90: 3498-3504.
    CrossrefPubMedGoogle Scholar
  • 5 Burgert TS, Taksali SE, Dziura J. et al. Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 2006; 91: 4287-4294.
    CrossrefPubMedGoogle Scholar
  • 6 Carter-Kent C, Yerian LM, Brunt EM. et al. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology 2009; 50: 1113-1120.
    CrossrefPubMedGoogle Scholar
  • 7 Chan DF, Li AM, Chu WC. et al. Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord 2004; 28: 1257-1263.
    CrossrefPubMedGoogle Scholar
  • 8 Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649-1657.
    CrossrefPubMedGoogle Scholar
  • 9 Cook JS, Hoffman RP, Stene MA, Hansen JR. Effects of maturational stage on insulin sensitivity during puberty. J Clin Endocrinol Metab 1993; 77: 725-730.
    PubMedGoogle Scholar
  • 10 Day CP, James OF. Steatohepatitis: a tale of two “hits”. Gastroenterology 1998; 114: 842-845.
    CrossrefPubMedGoogle Scholar
  • 11 Denzer C, Thiere D, Muche R. et al. Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J Clin Endocrinol Metab 2009; 94: 3872-3881.
    CrossrefPubMedGoogle Scholar
  • 12 Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881-887.
    CrossrefPubMedGoogle Scholar
  • 13 Ebbeling CB, Pawlak DB, Ludwig DS. Childhood Obesity: public-health crisis, common sense cure. Lancet 2002; 360: 473-482.
    CrossrefPubMedGoogle Scholar
  • 14 Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S. et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009; 58: 1538-1544.
    CrossrefPubMedGoogle Scholar
  • 15 Fishbein M, Castro F, Cheruku S. et al. Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J Clin Gastroenterol 2005; 39: 619-625.
    CrossrefPubMedGoogle Scholar
  • 16 Fishbein MH, Mogren C, Gleason T, Stevens WR. Relationship of hepatic steatosis to adipose tissue distribution in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2006; 42: 83-88.
    PubMedGoogle Scholar
  • 17 Franzese A, Vajro P, Argenziano A. et al. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997; 42: 1428-1432.
    CrossrefPubMedGoogle Scholar
  • 18 Guzzaloni G, Grugni G, Minocci A. et al. Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test. Int J Obes Relat Metab Disord 2000; 24: 772-776.
    CrossrefPubMedGoogle Scholar
  • 19 Hewitt KN, Pratis K, Jones ME, Simpson ER. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout mouse. Endocrinology 2004; 145: 1842-1848.
    CrossrefPubMedGoogle Scholar
  • 20 Inoue H, Shimizu I, Lu G. et al. Idoxifene and estradiol enhance antiapoptotic activity through estrogen receptor-beta in cultured rat hepatocytes. Dig Dis Sci 2003; 48: 570-580.
    CrossrefPubMedGoogle Scholar
  • 21 Jones ME, Thorburn AW, Britt KL. et al. Aromatasedeficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci U S A 2000; 97: 12735-12740.
    CrossrefPubMedGoogle Scholar
  • 22 Joseph AE, Saverymuttu SH, al-Sam S. et al. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991; 43: 26-31.
    CrossrefPubMedGoogle Scholar
  • 23 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.
    CrossrefPubMedGoogle Scholar
  • 24 Krssak M, Petersen KF, Dresner A. et al. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999; 42: 113-116.
    CrossrefPubMedGoogle Scholar
  • 25 Kubota N, Terauchi Y, Yamauchi T. et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002; 277: 25863-25866.
    CrossrefPubMedGoogle Scholar
  • 26 Kurth BM, Schaffrath ARosario. Die Verbreitung von Übergewicht und Adipositas bei Kindern und Jugendlichen in Deutschland. Bundesgesundheitsbl - Gesundheitsforsch - Gesundheitsschutz 2007; 50: 736-743.
    PubMedGoogle Scholar
  • 27 Lacort M, Leal AM, Liza M. et al. Protective effect of estrogens and catecholestrogens against peroxidative membrane damage in vitro. Lipids 1995; 30: 141-146.
    CrossrefPubMedGoogle Scholar
  • 28 Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000; 136: 734-738.
    CrossrefPubMedGoogle Scholar
  • 29 Loomba R, Hwang SJ, O’Donnell CJ. et al. Parental obesity and offspring serum alanine and aspartate aminotransferase levels: the Framingham heart study. Gastroenterology 2008; 134: 953-959.
    CrossrefPubMedGoogle Scholar
  • 30 Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. Hepatology 2009; 50: 1282-1293.
    CrossrefPubMedGoogle Scholar
  • 31 Louthan MV, Theriot JA, Zimmerman E. et al. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. J Pediatr Gastroenterol Nutr 2005; 41: 426-429.
    CrossrefPubMedGoogle Scholar
  • 32 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.
    CrossrefPubMedGoogle Scholar
  • 33 Manco M, Marcellini M, Giannone G, Nobili V. Correlation of serum TNF-alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. Am J Clin Pathol 2007; 127: 954-960.
    CrossrefPubMedGoogle Scholar
  • 34 Marion AW, Baker AJ, Dhawan A. Fatty liver disease in children. Arch Dis Child 2004; 89: 648-652.
    CrossrefPubMedGoogle Scholar
  • 35 Moran JR, Ghishan FK, Halter SA, Greene HL. Steatohepatitis in obese children: a cause of chronic liver dysfunction. Am J Gastroenterol 1983; 78: 374-377.
    PubMedGoogle Scholar
  • 36 Nielsen S, Guo Z, Johnson CM. et al. Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113: 1582-1588.
    CrossrefPubMedGoogle Scholar
  • 37 Nishino M, Hayakawa K, Nakamura Y. et al. Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: high frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR Am J Roentgenol 2003; 180: 129-134.
    CrossrefPubMedGoogle Scholar
  • 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: 119-128.
    CrossrefPubMedGoogle Scholar
  • 39 Nobili V, Marcellini M, Devito R. et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 2006; 44: 458-465.
    CrossrefPubMedGoogle Scholar
  • 40 Nobili V, Parkes J, Bottazzo G. et al. Performance of ELF serum markers in predicting fibrosis stage in pediatric non-alcoholic fatty liver disease. Gastroenterology 2009; 136: 160-167.
    CrossrefPubMedGoogle Scholar
  • 41 Omoya T, Shimizu I, Zhou Y. et al. Effects of idoxi - fene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress. Liver 2001; 21: 183-191.
    CrossrefPubMedGoogle Scholar
  • 42 Park HS, Han JH, Choi KM, Kim SM. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr 2005; 82: 1046-1051.
    CrossrefPubMedGoogle Scholar
  • 43 Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000; 30: 48-53.
    CrossrefPubMedGoogle Scholar
  • 44 Reinehr T, Roth CL. Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese children before and after weight loss. J Clin Endocrinol Metab 2008; 93: 4479-4485.
    CrossrefPubMedGoogle Scholar
  • 45 Sagi R, Reif S, Neuman G. et al. Nonalcoholic fatty liver disease in overweight children and adolescents. Acta Paediatr 2007; 96: 1209-1213.
    CrossrefPubMedGoogle Scholar
  • 46 Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986; 292: 13-15.
    CrossrefPubMedGoogle Scholar
  • 47 Schwimmer JB, Behling C, Newbury R. et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-649.
    CrossrefPubMedGoogle Scholar
  • 48 Schwimmer JB, Celedon MA, Lavine JE. et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585-1592.
    CrossrefPubMedGoogle Scholar
  • 49 Schwimmer JB, Deutsch R, Kahen T. et al. Prevalence of fatty liver in children and adolescents. Pediatrics 2006; 118: 1388-1393.
    CrossrefPubMedGoogle Scholar
  • 50 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.
    CrossrefPubMedGoogle Scholar
  • 51 Schwimmer JB, Khorram O, Chiu V, Schwimmer WB. Abnormal aminotransferase activity in women with polycystic ovary syndrome. Fertil Steril 2005; 83: 494-497.
    CrossrefPubMedGoogle Scholar
  • 52 Schwimmer JB, McGreal N, Deutsch R. et al. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 2005; 115: e561-e565.
    CrossrefPubMedGoogle Scholar
  • 53 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.
    CrossrefPubMedGoogle Scholar
  • 54 Schwimmer JB, Pardee PE, Lavine JE. et al. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008; 118: 277-283.
    CrossrefPubMedGoogle Scholar
  • 55 Setji TL, Holland ND, Sanders LL. et al. Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91: 1741-1747.
    CrossrefPubMedGoogle Scholar
  • 56 Stefan N, Kantartzis K, Haring HU. Causes and metabolic consequences of Fatty liver. Endocr Rev 2008; 29: 939-960.
    CrossrefPubMedGoogle Scholar
  • 57 Strauss RS, Barlow SE, Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr 2000; 136: 727-733.
    PubMedGoogle Scholar
  • 58 Tominaga K, Kurata JH, Chen YK. et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 1995; 40: 2002-2009.
    CrossrefPubMedGoogle Scholar
  • 59 Vajro P, Fontanella A, Perna C. et al. Persistent hyperaminotransferasemia resolving after weight reduction in obese children. J Pediatr 1994; 125: 239-241.
    CrossrefPubMedGoogle Scholar
  • 60 Vajro P, Franzese A, Valerio G. et al. Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children. J Pediatr 2000; 136: 739-743.
    CrossrefPubMedGoogle Scholar
  • 61 Veldhuis JD, Roemmich JN, Richmond EJ. et al. Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev 2005; 26: 114-146.
    CrossrefPubMedGoogle Scholar
  • 62 Vos MB, Barve S, Joshi-Barve S. et al. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 2008; 47: 481-485.
    CrossrefPubMedGoogle Scholar
  • 63 Wabitsch M, Moß A, Hauner H. et al. Therapie der Adipositas im Kindes- und Jugendalter. AWMF-Leitlinien-Register. 2009 050/002..
    PubMedGoogle Scholar
  • 64 Weiss R, Dufour S, Groszmann A. et al. Low adiponectin levels in adolescent obesity: a marker of increased intramyocellular lipid accumulation. J Clin Endocrinol Metab 2003; 88: 2014-2018.
    CrossrefPubMedGoogle Scholar
  • 65 Weiss R, Dziura J, Burgert TS. et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362-2374.
    CrossrefPubMedGoogle Scholar
  • 66 Weyer C, Funahashi T, Tanaka S. et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930-1935.
    CrossrefPubMedGoogle Scholar
  • 67 Wieckowska A, McCullough AJ, Feldstein AE. Non-invasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology 2007; 46: 582-589.
    CrossrefPubMedGoogle Scholar
  • 68 Yamauchi T, Kamon J, Minokoshi Y. et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 08: 1288-1295.
    CrossrefPubMedGoogle Scholar
  • 69 Yamauchi T, Kamon J, Waki H. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 07: 941-946.
    CrossrefPubMedGoogle Scholar
  • 70 Yokota T, Oritani K, Takahashi I. et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000; 96: 1723-1732.
    PubMedGoogle Scholar