Re: Estrada et al.,“Children's Hospital Association Consensus Statements for Comorbidities of Childhood Obesity”

To the Editor:

We read with interest the recent pediatric weight management guidelines published by Estrada and colleagues from the Focus for a Fitter Future Working Group of National Association of Children's Hospitals and Related Institutions (NACHRI). ¹ While applauding the efforts of the authors for the document generated with the goal to provide guidance to practitioners regarding management of weight-related comorbidities, we were somewhat disappointed regarding recommendations provided for evaluation and treatment of nonalcoholic fatty liver disease (NAFLD) and minimal detail provided regarding sleep apnea.

The diagnosis of NAFLD is a diagnosis of exclusion requiring exclusion of other causes of liver disease, including medication-induced liver disease. Use of “worsening” aminotransferases as an indicator for further evaluation can be problematic. The authors cited the recent publication by Schwimmer and colleagues regarding elevation of lab normal ranges without mentioning the recommended normative cut-off ranges proposed by the publication of 22.1 for girls and 25.8 for boys, ² proposing screening cut-off ranges for further evaluation per Figure 5 of alanine aminotransferase (ALT) 2–3 times the upper range of normal (in the 40 to 60 range). A recent publication by Molleston and colleagues of children enrolled in the The Nonalcoholic Steatohepatitis Research Network (NASH CRN) study showed the pitfalls of use of normal ALT (<44 in girls and <50 in boys) for reassurance regarding fatty liver disease given that 24% of the children with normal ALT had elevation of the NAFLD Activity Score (NAS) and 24% had borderline nonalcoholic steatohepatitis (NASH). ³ Additionally, a more recent publication by Schwimmer and colleagues^4,5 reported that ALT 2 times the clinical upper limit of normal (ULN) had a sensitivity of 57% and specificity of 71% for NAFLD, demonstrating the limitation of these recommendations' threshold for ALT as a screening tool. Further, it was determined that 21% of children identified by pediatricians as having suspected NAFLD by screening did not have liver disease. Of those who were referred by pediatricians as having suspected NAFLD who actually had liver disease identified, 22% had a liver disease other than NAFLD (most commonly, autoimmune hepatitis). ⁵

For patients warranting further screening for causes of aminotransferase elevation and screening for causes of underlying liver disease, an extensive workup is proposed to screen for infectious, metabolic, and autoimmune liver disease without mention of checking a serum albumin to assess for synthetic function or exclusion of nonhepatic causes of aminotransferase elevation from muscle sources (creatine kinase) given that elevation in aminotransferases can be observed in children with underlying muscular dystrophy.^4,6 While the recommendation by the authors is to rule out other forms of liver disease with worsening liver enzyme values, we would suggest that the literature supports ruling out other forms of liver disease, even if the value is stable at an ALT level of 1.5 times the ULN, if it has been elevated for >6 months. ⁴ The treatment paradigm should include weight management as discussed, in addition to prevention of acquisition of other causes of liver disease/hepatic impairment. Children with NAFLD should receive vaccinations/booster immunization against other preventable causes of liver disease in children, such as hepatitis A and B if nonimmune (a recent study published by Mehta and colleagues found that 72% children in a pediatric NAFLD cohort were nonimmune to hepatitis B attributed to decreased immune response in the setting of obesity ⁷ ). As the authors mention, families should be counseled to minimize exposure to hepatotoxic agents, such as ethanol, and hepatotoxic medications.

The prevalence of sleep apnea is estimated to be 4% in children and 13–59% among obese children dependent upon criteria used.^8,9 Sleep apnea has been shown to correlate with symptoms of attention deficit hyperactivity disorder, ¹⁰ hypertension, ¹¹ and neurocognitive deficits ¹² and recently reported as a contributor to development of progressive liver disease among children with NAFLD. ¹³ We are glad to note that 80% of the NACHRI-associated weight management programs screen for sleep apnea and emphasize the importance of careful screening for the presence of symptoms.