Elsevier

Clinics in Liver Disease

Volume 8, Issue 3, August 2004, Pages 549-558
Clinics in Liver Disease

Nonalcoholic fatty liver disease in the pediatric population

https://doi.org/10.1016/j.cld.2004.04.010Get rights and content

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Terminology

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of histologic findings ranging from macrovesicular steatosis alone (simple steatosis) to macrovesicular or mixed macro- and microvesicular steatosis with inflammation and evidence of cellular injury (NASH). In NASH, the mixed inflammatory infiltrate may be associated with Mallory hyaline or ballooning degeneration of hepatocytes. Evidence of chronic liver injury may be manifest by fibrotic changes. These changes may be severe

Differential diagnosis

NASH and NAFLD are histologic diagnoses within a particular context. Potential alternative etiologies exhibiting steatosis or steatohepatitis include the following:

  • Toxins (ethanol)

  • Drugs (amiodarone, glucocorticoids, valproate, L-asparaginase)

  • Inborn errors of metabolism (urea cycle, fatty acid oxidation, organic acidemia, glycogen storage, carnitine deficiency, abetalipoproteinemia, cystic fibrosis)

  • Storage disorders (Wilson's disease, hemochromatosis, alpha-1-antitrypsin)

  • Infection (hepatitic C)

Prevalence

Estimates of pediatric NAFLD prevalence are confounded by the same problems confronted by those attempting to estimate adult NAFLD prevalence. These problems include finding a sample population free of geographic, referral, or selection bias and lack of reliable surrogate markers for hepatic histology. Thus, investigators have inferred prevalence based on specific radiologic criteria or elevated serum aminotransferases in selected obese populations. Radiology findings include diffuse

Demographics

Remarkable uniformity exists within the pediatric patients described with NASH in several studies over the past two decades. Review of reports from North America [4], [5], [6], Asia [3], and Australia [7] demonstrate a narrow mean age of presentation ranging from 11.6 to 13.5 years. In all reports, boys outnumber girls, usually in a 2:1 ratio. No information is available as to why NASH presents at a particular age so regularly. Children this age may visit the doctor more regularly than older

Clinical presentation

As in adults, many children with NASH are asymptomatic. In our experience most care providers do not screen for NASH in obese children, and many are unaware that NASH is a common cause of liver disease. Thus, most children are diagnosed after referral to pediatric gastroenterology with an alternative chief complaint. Findings may include a fatty liver on diagnostic imaging obtained for an unrelated reason, detection of an enlarged liver on routine physical examination by a physician, or

Laboratory evaluation

Every series of pediatric NASH uniformly reports elevated serum ALT with means ranging from 103 to 208 U/L. Individual serum ALT ranges from slightly over the upper limit of normal to 10 times the upper limit of normal [4], [5], [6], [7]. Although “normal ALT” NASH is reported in adults [21], examples are not reported in children. We have two children with normal ALT and biopsy-demonstrated NASH who underwent biopsy for an alternative reason. Apparently, normal ALT NASH in children may not be

Histology

NASH is a histologic diagnosis made within a clinical context. The context requires elimination of other causes of steatohepatitis in the differential diagnosis. For adult NASH, histologic definition is evolving but generally requires macrovesicular steatosis, mixed lobular inflammation, and evidence of cell injury. Cell injury is considered manifest by hepatocellular ballooning or Mallory hyaline. Fibrosis, if present, is generally a zone 3 perisinusoidal fibrosis. Brunt et al [22] suggested a

Treatment

Day and James [24] proposed that NASH is a consequence of two successive “hits”; the first requisite being fatty infiltration of the liver, the second resulting from oxidative stress. The first hit in most cases of NASH is due to obesity and concomitant insulin resistance, which is a finding in pediatric [6] as well as adult [25] NASH. The second hit may be due to a variety of environmental or genetic factors. Obese children have lower levels of serum antioxidants [26], [27], which may be due

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  • Cited by (0)

    This work was supported in part by NIH grants 1 U01 DK 61734-01 and M01 RR00827.

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