Recognition and Management of Children with Nonalcoholic Fatty Liver Disease
Journal of Clinical Outcomes Management. 2016 March;23(3)
References
Comorbidities
NAFLD is associated with obesity, insulin resistance and diabetes, cardiovascular disease, the metabolic syndrome [23], decreased quality of life [24,25], and obstructive sleep apnea (OSA). These associations generally hold even after controlling for the other confounders listed. It is important to note that these data come largely from cross-sectional studies and direct causation has yet to be determined.
Insulin resistance in particular is strongly associated with NAFLD—so much so, in fact, that some consider it to be the hepatic manifestation of the metabolic syndrome. Additionally, children with features of the metabolic syndrome are more likely to have advanced histologic features of NAFLD [23]. There are also intriguing data from small pediatric studies to suggest that OSA may contribute to the development of hepatic fibrosis. In one study of 25 children with biopsy-proven NAFLD, for example, the presence of OSA and hypoxemia correlated with the degree of hepatic fibrosis [26]. In a slightly larger study of 65 children, OSA was also strongly associated with significant hepatic fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23–7.42; P < 0.001). The duration of hypoxemia also correlated with histologic findings of inflammation and circulating biomarkers of apoptosis and fibrogenesis [27].
Other Laboratory Tests
Several studies have documented an association between elevated gamma-glutamyl transferase (GGT) and hepatic fibrosis [28,29], though others have been conflicting [30,31]. Pediatric studies have also demonstrated an inverse correlation between NASH and total bilirubin [32], serum potassium [33], and serum ceruloplasmin [34]. In addition, there are a number of serum biomarkers or biomarker panels commercially available for use in adults. Because similar efficacy data are unavailable in children, however, serum biomarkers should be primarily used for research purposes only.
Who should be screened for NAFLD? And how?
Published professional society recommendations differ significantly with regards to screening. In 2007, the American Academy of Pediatrics suggested screening obese children over 10 years of age or overweight children with additional risk factors with biannual liver tests [35]. There were no management recommendations made for elevated aminotransferase levels other than for subspecialty referral. In 2012, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommended obtaining an ultrasound and liver tests in every obese child [36]. One month later, however, the American Gastroenterological Association, American Association for the Study of Liver Disease, and the American College of Gastroenterology published joint guidelines without screening recommendations “due to a paucity of evidence” [37].
Because these statements conflict and are based heavily on expert opinion, one should consider the risks, benefits, and costs to screening large numbers of patients. Until additional research clarifies this controversy, we suggest that providers individualize their screening practices to their population and the risks of each individual patient. For example, we would consider screening children who are obese; Hispanic or Asian; have multiple features of the metabolic syndrome; and/or those who have a family history of NAFLD. Further, we recommend screening children for NAFLD with serum liver enzymes only and not with ultrasonography.
Case Continued: Laboratory Results
ALT and GGT tests are ordered and the results are as follows:
