Case-Based Review

Recognition and Management of Children with Nonalcoholic Fatty Liver Disease

Journal of Clinical Outcomes Management. 2016 March;23(3)

References

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Our suggested approach to these patients is shown in the Figure. Specifically, for older, asymptomatic, overweight or obese children with a mildly elevated ALT and normal direct bilirubin level, we believe that a trial of lifesyle modification can be safely initated prior to initiation of extensive laboratory testing or referral for biopsy. With that said, for children with any of the other “red flags” listed in the Table, early referral to an expert should be strongly considered.

Case Continued: Biopsy Results

You refer your patients to a gastroenterologist. Tests for viral hepatitis, A1A deficiency, celiac disease, muscle disorders, Wilson’s disease, and AIH are negative. Ultimately, a liver biopsy is performed on all 3 children without complications. The results are presented below.

What is the treatment of NAFLD?

Lifestyle Modification

Lifestyle modifications are the mainstay of treatment for NAFLD. In adult studies, weight loss of more than 5% reduces hepatic steatosis whereas weight loss of more than 9% improves or eliminates NASH [47]. We recommend that children engage in age-appropriate, enjoyable, moderate- or vigorous-intensity aerobic activity for 60 minutes a day [48]. In addition, there should be a focus on reducing sedentary behavior by limiting screen time and a concerted effort to engage the family in lifestyle modifications.

Dietary interventions to treat NAFLD are less concrete but there is a growing body of literature to suggest that dietary fructose is particularly harmful. In adults, for example, fructose consumption is associated with the development of NAFLD [49] and hepatic fibrosis [50]. Recent data in adolescents has similarly documented an association between NAFLD incidence and energy-adjusted fructose intake [51]. It is worth highlighting that these clinical findings are also biologically plausible, as fructose is primarily metabolized within hepatocytes and has recently been shown to increase de novo lipogenesis [52,53]. In general, we suggest a well-balanced diet of unprocessed foods—that is, with limited added sugars—sufficient to induce gradual weight loss in older children or body weight maintenance in younger children.

Medications

Vitamin E is the only medication with proven efficacy in children, as demonstrated in the TONIC trial [20]. TONIC was a double-blind, multicenter, placebo-controlled study with 3 treatment arms: 800 IU of vitamin E daily, 1000 mg of metformin daily, or placebo. Metformin did not reduce the serum ALT or significantly improve liver histology and should therefore not be used for these indications. However, patients treated with vitamin E had a statistically significant improvement in the NAFLD activity score (a histologic grading system comprising steatosis, inflammation, and hepatocyte ballooning) and resolution of NASH when compared to placebo. For these reasons—as well as a paucity of other viable treatment options—vitamin E is routinely prescribed for children with biopsy-proven NASH. However, the long- term risks of high-dose vitamin E therapy in children are largely unknown.

Polyunsaturated fats such as docosahexaenoic acid (DHA) [54] and probiotics such as VSL #3 [55] have showed efficacy reducing hepatic steatosis in small, randomized clinical trials. Both medications need to be further validated before they can be recommended for use in children. Conversely, ursodeoxycholic acid has not been found to be efficacious in children with NAFLD [56], whereas phase IIb data on cysteamine is expected soon. There are currently insufficient data to recommend bariatric surgery as treatment for NAFLD in adolescence.