Elsevier

Clinics in Liver Disease

Volume 10, Issue 1, February 2006, Pages 109-131
Clinics in Liver Disease

Nonalcoholic Fatty Liver Disease in Children

https://doi.org/10.1016/j.cld.2005.10.007Get rights and content

Section snippets

Childhood obesity/overweight

Childhood obesity has become a major public health problem [1], [2], [3], [4]. Current estimates put the number of obese children at more than 20 million worldwide. Since the mid-1990s, the prevalence of overweight children in the United States has increased dramatically. Certain ethnic groups are particularly severely affected, with a 22% rise in African American children, 22% in Hispanic children, and 12% in non-Hispanic white children, according to 1998 data [1]. The same rise in childhood

Prevalence of childhood nonalcoholic fatty liver disease

It is difficult to determine the overall prevalence of childhood NAFLD. Most clinical reports suffer from defects of research design—mainly ascertainment bias—and therefore cannot address the question of disease prevalence. Relevant studies have examined the prevalence of fatty liver or abnormal serum aminotransferase levels in large, unselected groups of overweight or obese children. For technical reasons these studies tend to underestimate prevalence by failing to identify mild hepatic

Pathogenesis

Hyperinsulinemia, in association with insulin resistance, is now recognized as an essential component of the disease mechanism of NAFLD [49], [50], [51], [52], [53], [54]. In many adult patients, NAFLD seems to be the hepatic presentation of the metabolic syndrome. Increased concentrations of free fatty acids in plasma or in hepatocytes probably play an important role in the development of steatosis and inflammation [55], [56]. Insulin inhibits oxidation of free fatty acids, and thus

Hyperinsulinemia with insulin resistance in childhood nonalcoholic fatty liver disease

Accumulating data support the role of hyperinsulinemia with insulin resistance in childhood NAFLD [61], [62]. In a consecutive series of 43 children who had biopsy-proven NAFLD from San Diego, 95% met the criteria for insulin resistance when results for the homeostasis model of insulin resistance (HOMA-IR) and a related arithmetic estimate of insulin resistance (QUICK-I) were combined [61]. Children in this cohort were mostly male (70%), Hispanic American (53%), and obese (88%).

Adipocytokines

Adipose tissue acts as an endocrine tissue and produces metabolically active proteins (hormones or cytokines) known as adipocytokines. Those that modulate insulin action include tumor necrosis factor-α, adiponectin, and resistin. Adiponectin may play the most important role in the pathogenesis of NAFLD. Numerous studies indicate that obesity in children is associated with low concentrations of serum adiponectin [74], [75]. The severity of insulin resistance in obese children is inversely

Clinical findings in childhood nonalcoholic fatty liver disease

Numerous reports have provided an increasingly comprehensive description of NAFLD in children [51], [61], [66], [86], [87], [88], [89], [90], [91], [92], [93], [94]. Whereas NASH in adults was first described in the late 1970s, the first few case reports of childhood NASH appeared in the English language literature in the mid-1980s. The first large pediatric clinical series included 36 patients from various ethnic backgrounds collected prospectively and consecutively between 1985 and 1995 at

Liver histology in childhood nonalcoholic fatty liver disease

The diagnosis of NAFLD requires liver histology [100], [101], [102]. Some fat is expected to be present (involving at least 5% of the hepatocytes), except perhaps in advanced cirrhosis, which may appear to be cryptogenic [103], [104]. The fat globules may be small but are macrovesicular. When fat is present only as a bland lesion without inflammation, it is called simple steatosis. NASH implies the presence of inflammation, fibrosis, or both in addition to steatosis. The infiltrate consists of

Genetic/metabolic diseases associated with nonalcoholic fatty liver disease

Although hepatic steatosis in patients who have cystic fibrosis is probably caused different disease mechanisms from those operating in NAFLD, some genetic/metabolic diseases also involve hyperinsulinemia and hepatic insulin resistance and are characterized by chronic liver injury indistinguishable from NAFLD. Estimates of how many children who have NAFLD have cirrhosis do not include individuals who have these disorders and advanced liver damage. Bardet-Biedl and Alström syndromes are classic

Clinical approach to diagnosis of childhood nonalcoholic fatty liver disease

The typical patient who has childhood NAFLD is 10 to 14 years old, but patients may be as young as 4 to 5 years old. Most are overweight or obese by age- and gender-normative reference data. Those who are not overweight or obese are often tall for age and with weight on the same percentile as height, consistent with generalized overnutrition. Symptoms of liver disease are rare, but some children present with nonspecific abdominal pain. If serum aminotransferase levels are elevated, the overall

Treatment of childhood nonalcoholic fatty liver disease

Treatment currently consists of eliminating or reducing risk factors known to be associated with NAFLD. Comprehensive therapeutic studies are lacking in childhood NAFLD. Weight loss seems to improve the liver disease as judged by improvement in serum aminotransferase levels; histologic improvement has not been studied. Various pharmacologic interventions have been proposed, but few have been investigated rigorously.

Summary

NAFLD is an important liver disease in both adults and children. The entire range of liver involvement characterizing NAFLD can occur in children: hepatic macrovesicular steatosis without inflammation, steatosis with inflammation or fibrosis, and cirrhosis. NAFLD may occur in very young (preschool) children, with a male predominance among children and adolescents. If at all symptomatic, children often present with vague abdominal pain. NAFLD may be the hepatic manifestation of the metabolic

First page preview

First page preview
Click to open first page preview

References (174)

  • T.A. Nicklas et al.

    Children's meal patterns have changed over a 21-year period: the Bogalusa Heart Study

    J Am Diet Assoc

    (2004)
  • H. Kaur et al.

    Duration of television watching is associated with increased body mass index

    J Pediatr

    (2003)
  • D.M. Matheson et al.

    Children's food consumption during television viewing

    Am J Clin Nutr

    (2004)
  • E.A. Vandewater et al.

    Linking obesity and activity level with children's television and video game use

    J Adolesc

    (2004)
  • A. Fagot-Campagna et al.

    Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective

    J Pediatr

    (2000)
  • S. Saadeh et al.

    The utility of radiological imaging in nonalcoholic fatty liver disease

    Gastroenterology

    (2002)
  • U.L. Mathiesen et al.

    Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases

    Dig Liver Dis

    (2002)
  • R.S. Strauss et al.

    Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents

    J Pediatr

    (2000)
  • G. Marchesini et al.

    Association of nonalcoholic fatty liver disease with insulin resistance

    Am J Med

    (1999)
  • I.R. Willner et al.

    Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease

    Am J Gastroenterol

    (2001)
  • G. Pagano et al.

    Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association

    Hepatology

    (2002)
  • S. Chitturi et al.

    NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome

    Hepatology

    (2002)
  • C.P. Day

    Pathogenesis of steatohepatitis

    Best Prac Res Clin Gastroenterol

    (2002)
  • J.B. Schwimmer et al.

    Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease

    J Pediatr

    (2003)
  • J.A. Yanovski et al.

    When a child can't clean her neck

    J Pediatr

    (2001)
  • R. Ohmori et al.

    Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease

    J Am Coll Cardiol

    (2005)
  • A. Uygun et al.

    Serum leptin levels in patients with nonalcoholic steatohepatitis

    Am J Gastroenterol

    (2000)
  • P. Vajro et al.

    Persistent hypertransaminasemia resolving after weight reduction in obese children

    J Pediatr

    (1994)
  • A.D. Baldridge et al.

    Idiopathic steatohepatitis in childhood: a multicenter retrospective study

    J Pediatr

    (1995)
  • N. Kocak et al.

    Obesity: a cause of steatohepatitis in children

    Am J Gastroenterol

    (2000)
  • R.S. Strauss et al.

    Epidemic increase in childhood overweight, 1986–1998

    JAMA

    (2001)
  • C.E. Flodmark et al.

    New insights into the field of children and adolescents' obesity: the European perspective

    Int J Obes Relat Metab Disord

    (2004)
  • M. Yoshinaga et al.

    Rapid increase in the prevalence of obesity in elementary school children

    Int J Obes Relat Metab Disord

    (2004)
  • T. Lobstein et al.

    Obesity in children and young people: a crisis in public health

    Obes Rev

    (2004)
  • M.S. Tremblay et al.

    Secular trends in the body mass index of Canadian children

    Can Med Assoc J

    (2000)
  • P.T. James et al.

    The obesity epidemic, metabolic syndrome and future prevention strategies

    Eur J Cardiovasc Prev Rehabil

    (2004)
  • P.M. Canning et al.

    Prevalence of overweight and obesity in a provincial population of Canadian preschool children

    Can Med Assoc J

    (2004)
  • P. Bundred et al.

    Prevalence of overweight and obese children between 1989 and 1998: population based series of cross sectional studies

    BMJ

    (2001)
  • J.A. Nelson et al.

    Childhood overweight in a New York City WIC population

    Am J Public Health

    (2004)
  • L.E. Thorpe et al.

    Childhood obesity in New York City elementary school students

    Am J Public Health

    (2004)
  • T.J. Cole et al.

    What is the best measure of adiposity change in growing children: BMI, BMI %, BMI z-score or BMI centile?

    Eur J Clin Nutr

    (2005)
  • C. Power et al.

    Measurement and long-term health risks of child and adolescent fatness

    Int J Obes Relat Metab Disord

    (1997)
  • W. Kiess et al.

    Clinical aspects of obesity in childhood and adolescence

    Obes Rev

    (2001)
  • R.J. Kuczmarski et al.

    CDC growth charts: United States

    Adv Data

    (2000)
  • T.J. Cole et al.

    Establishing a standard definition for child overweight and obesity worldwide: international survey

    BMJ

    (2000)
  • R. Weiss et al.

    Obesity and the metabolic syndrome in children and adolescents

    N Engl J Med

    (2004)
  • H.D. McCarthy et al.

    Central overweight and obesity in British youth aged 11–16 years: cross sectional surveys of waist circumference

    BMJ

    (2003)
  • P.T. Katzmarzyk

    Waist circumference percentiles for Canadian youth 11–18y of age

    Eur J Clin Nutr

    (2004)
  • A.M. Fredriks et al.

    Are age references for waist circumference, hip circumference and waist-hip ratio in Dutch children useful in clinical practice?

    Eur J Pediatr

    (2005)
  • H.D. McCarthy et al.

    Trends in waist circumferences in young British children: a comparative study

    Int J Obes Relat Metab Disord

    (2005)
  • Cited by (0)

    This work was supported in part by the Canadian Association of Gastroenterology/Nestlé/CIHR Pediatric Nutrition Fellowship award (DRM) and the Metabolism Research Program/Mead-Johnson fund (to EAR).

    View full text