Definitive Diagnosis and Assessment of Risk for Nonalcoholic Fatty Liver Disease in Children and Adolescents

Jeffrey B. Schwimmer

doi:10.1055/s-2007-985075

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2007; 27(3): 312-318
DOI: 10.1055/s-2007-985075

Definitive Diagnosis and Assessment of Risk for Nonalcoholic Fatty Liver Disease in Children and Adolescents

Jeffrey B. Schwimmer¹

¹Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego; and Rady Children's Hospital and Health Center, San Diego, California

Abstract

ABSTRACT

This review covers the diagnosis and epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in children and adolescents. Pediatric NAFLD remains a clinicopathologic diagnosis requiring direct demonstration of liver steatosis and the exclusion of other causes of fatty liver and/or hepatitis. NAFLD is the most common cause of chronic liver disease in children. The number of children with NAFLD presents a major public health crisis. Age, sex, race, ethnicity, and body habitus all influence the risk for NAFLD. The epidemiology of pediatric NAFLD should inform future attempts to develop rigorously evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology in children and adolescents. Our future ability to prevent and treat pediatric NAFLD is dependent upon such work.

KEYWORDS

Nonalcoholic fatty liver disease - nonalcoholic steatohepatitis - obesity - children - epidemiology

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Referenzen

REFERENCES

1 Zelman S. The liver in obesity. Arch Intern Med. 1958; 90 141-156
2 Ludwig J, Viggiano T R, McGill D B, Oh B J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980; 55 434-438
3 Moran J R, Ghishan F K, Halter S A, Greene H L. Steatohepatitis in obese children: a cause of chronic liver dysfunction. Am J Gastroenterol. 1983; 78 374-377
4 Chan D F, Li A M, Chu W C et al.. Hepatic steatosis in obese Chinese children. Int J Obes Relat Metab Disord. 2004; 28 1257-1263
5 Guzzaloni G, Grugni G, Minocci A, Moro D, Morabito F. 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
6 Perseghin G, Bonfanti R, Magni S et al.. Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease. Am J Physiol Endocrinol Metab. 2006; 291 E697-E703
7 Radetti G, Kleon W, Stuefer J, Pittschieler K. Non-alcoholic fatty liver disease in obese children evaluated by magnetic resonance imaging. Acta Paediatr. 2006; 95 833-837
8 Burgert T S, Taksali S E, 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
9 Rashid M, Roberts E A. Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr. 2000; 30 48-53
10 Schwimmer J B, Behling C, Newbury R et al.. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005; 42 641-648
11 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
12 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
13 Yajima Y, Ohta K, Narui T, Abe R, Suzuki H, Ohtsuki M. Ultrasonographical diagnosis of fatty liver: significance of the liver-kidney contrast. Tohoku J Exp Med. 1983; 139 43-50
14 Bydder G M, Chapman R W, Harry D, Bassan L, Sherlock S, Kreel L. Computed tomography attenuation values in fatty liver. J Comput Tomogr. 1981; 5 33-35
15 Jacobs J E, Birnbaum B A, Shapiro M A et al.. Diagnostic criteria for fatty infiltration of the liver on contrast-enhanced helical CT. AJR Am J Roentgenol. 1998; 171 659-664
16 Kim M J, Mitchell D G, Ito K, Kim P N. Hepatic MR imaging: comparison of 2D and 3D gradient echo techniques. Abdom Imaging. 2001; 26 269-276
17 Rinella M E, McCarthy R, Thakrar K et al.. Dual-echo, chemical shift gradient-echo magnetic resonance imaging to quantify hepatic steatosis: implications for living liver donation. Liver Transpl. 2003; 9 851-856
18 Fishbein M H, Gardner K G, Potter C J, Schmalbrock P, Smith M A. Introduction of fast MR imaging in the assessment of hepatic steatosis. Magn Reson Imaging. 1997; 15 287-293
19 Fishbein M, Smith M, Li B U. A rapid MRI technique for the assessment of hepatic steatosis in a subject with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. J Pediatr Gastroenterol Nutr. 1998; 27 224-227
20 Fishbein M H, Miner M, Mogren C, Chalekson J. The spectrum of fatty liver in obese children and the relationship of serum aminotransferases to severity of steatosis. J Pediatr Gastroenterol Nutr. 2003; 36 54-61
21 Thomsen C, Becker U, Winkler K, Christoffersen P, Jensen M, Henriksen O. Quantification of liver fat using magnetic resonance spectroscopy. Magn Reson Imaging. 1994; 12 487-495
22 Wong W F, Northrup S R, Herrick R C, Glombicki A P, Wood R P, Morrisett J D. Quantitation of lipid in biological tissue by chemical shift magnetic resonance imaging. Magn Reson Med. 1994; 32 440-446
23 Schwimmer J B, Middleton M S, Deutsch R, Lavine J E. A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2005; 21 871-879
24 Brunt E M, Janney C G, Di Bisceglie A M, Neuschwander-Tetri B A, Bacon B R. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999; 94 2467-2474
25 Brunt E M. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001; 21 3-16
26 Kleiner D E, Brunt E M, Van Natta M et al.. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41 1313-1321
27 Committee on Prevention of Obesity in Children and Youth .Preventing Childhood Obesity: Health in the Balance. Washington, DC; The National Academies Press 2005
28 Barlow S E, Dietz W H. Obesity evaluation and treatment: Expert Committee recommendations. The Maternal and Child Health Bureau, Health Resources and Services Administration and the Department of Health and Human Services. Pediatrics. 1998; 102 E29
29 Speiser P W, Rudolf M C, Anhalt H et al.. Childhood obesity. J Clin Endocrinol Metab. 2005; 90 1871-1887
30 Riley M R, Bass N M, Rosenthal P, Merriman R B. Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists. J Pediatr. 2005; 147 839-842
31 Nguyen T T, Keil M F, Russell D L et al.. Relation of acanthosis nigricans to hyperinsulinemia and insulin sensitivity in overweight African American and white children. J Pediatr. 2001; 138 474-480
32 Schwimmer J B, Deutsch R, Rauch J B, Behling C, Newbury R, Lavine J E. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003; 143 500-505
33 Fishbein M, Mogren J, Mogren C, Cox S, Jennings R. 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
34 Tazawa Y, Noguchi H, Nishinomiya F, Takada G. Serum alanine aminotransferase activity in obese children. Acta Paediatr. 1997; 86 238-241
35 Nadeau K J, Klingensmith G, Zeitler P. Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase. J Pediatr Gastroenterol Nutr. 2005; 41 94-98
36 Adams L A, Feldstein A E, Lindor K D, Angulo P. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology. 2004; 39 909-914
37 Evans H M, Shaikh M G, McKiernan P J et al.. Acute fatty liver disease after suprasellar tumor resection. J Pediatr Gastroenterol Nutr. 2004; 39 288-291
38 Jonas M M, Krawczuk L E, Kim H B, Lillehei C, Perez-Atayde A. Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome. Liver Transpl. 2005; 11 108-110
39 Nakajima K, Hashimoto E, Kaneda H et al.. Pediatric nonalcoholic steatohepatitis associated with hypopituitarism. J Gastroenterol. 2005; 40 312-315
40 Schwimmer J B, Deutsch R, Kahen T, Lavine J E, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006; 118 1388-1393
41 Strauss R S, Barlow S E, Dietz W H. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr. 2000; 136 727-733
42 Quiros-Tejeira R E, Rivera C A, Ziba T T, Mehta N, Smith C W, Butte N F. Risk for nonalcoholic fatty liver disease in Hispanic youth with BMI > or = 95th percentile. J Pediatr Gastroenterol Nutr. 2007; 44 228-236
43 Baldridge A D, Perez-Atayde A R, Graeme-Cook F, Higgins L, Lavine J E. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J Pediatr. 1995; 127 700-704
44 Manton N D, Lipsett J, Moore D J, Davidson G P, Bourne A J, Couper R T. Non-alcoholic steatohepatitis in children and adolescents. Med J Aust. 2000; 173 476-479
45 Lavine J E, Schwimmer J B. Pediatric non-alcoholic steatohepatitis. In: Farrell G, George J, Hall P, McCollough A Non-alcoholic Steatohepatitis. Oxford, UK; Blackwell Publishing 2004: 229-240
46 Schwimmer J B, McGreal N, Deutsch R, Finegold M, Lavine J E. The influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005; 115 e561-e565
47 Kinugasa A, Tsunamoto K, Furukawa N, Sawada T, Kusunoki T, Shimada N. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gastroenterol Nutr. 1984; 3 408-414
48 Schwimmer J B, Burwinkle T M, Varni J W. Health-related quality of life of severely obese children and adolescents. JAMA. 2003; 289 1813-1819
49 Pinhas-Hamiel O, Dolan L M, Daniels S R, Standiford D, Khoury P R, Zeitler P. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr. 1996; 128 608-615
50 Gower B A. Syndrome X in children: influence of ethnicity and visceral fat. Am J Hum Biol. 1999; 11 249-257
51 Crawford P B, Story M, Wang M C, Ritchie L D, Sabry Z I. Ethnic issues in the epidemiology of childhood obesity. Pediatr Clin North Am. 2001; 48 855-878
52 Ogden C L, Flegal K M, Carroll M D, Johnson C L. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA. 2002; 288 1728-1732
53 Louthan M V, Theriot J A, Zimmerman E, Stutts J T, McClain C J. Decreased prevalence of nonalcoholic fatty liver disease in black obese children. J Pediatr Gastroenterol Nutr. 2005; 41 426-429
54 Xanthakos S, Miles L, Bucuvalas J, Daniels S, Garcia V, Inge T. Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents. Clin Gastroenterol Hepatol. 2006; 4 226-232
55 Tominaga K, Kurata J H, Chen Y K et al.. Prevalence of fatty liver in Japanese children and relationship to obesity: an epidemiological ultrasonographic survey. Dig Dis Sci. 1995; 40 2002-2009

Jeffrey B SchwimmerM.D.

UCSD Medical Center, 200 West Arbor Drive

San Diego, CA 92103-8450