Nonalcoholic Fatty Liver Disease in Children – Where to Now? :

In a recently released study in Pediatrics(10.1542/peds.2020-009829), Dr. Toshifumi Yodoshi and colleagues share results of an investigation into the frequency of alternative causes of liver disease among overweight and obese children suspected of having non-alcoholic fatty liver disease (NAFLD). This retrospective two-center chart review study included an ethnically diverse cohort of 900 children <18-years-old with body mass index (BMI) >85% and elevated serum aminotransferases and/or hepatic steatosis on an imaging study. Children were a median of 13 years of age, 76% were severely obese, and the median alanine aminotransferase (ALT) level at presentation was 64 U/L; 358 children (40%) underwent clinically indicated liver biopsy. Of note, almost half (46%) of those undergoing biopsy were diagnosed with non-alcoholic steatohepatitis (NASH – the most severe form of NAFLD).  The research aimed to find out how many of those with suspected NAFLD had other diagnoses, and the answer was “many less than expected.”

I’d like to back up just a minute and put this highly informative study into some perspective. As reported in AAP News¹, in 2016 the American Academy of Pediatrics endorsed new guidelines that recommend screening for NAFLD with a serum alanine aminotransferase in children ages 9–11-years-old with either obesity (BMI>95%) or overweight (BMI>85%) with risk factors (including central adiposity, insulin resistance, pre‐diabetes or diabetes, dyslipidemia, sleep apnea and family history). If an elevation over 2x the upper limit of normal persists for more than 3 months, additional work up and/or referral to gastroenterology to rule out specific treatable conditions is advised. This recommendation aligns with guidance from the highly respected North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).² While interesting treatments for NAFLD are on the horizon³, the only evidence-based treatment currently available is lifestyle change with weight loss, calorie restriction and increased physical exercise. Thus, the main impetus for evaluation and referral of children with persistently elevated serum ALT is to avoid missing other important or progressive conditions not treated by lifestyle change. These include auto-immune hepatitis, Wilson disease, hemochromatosis, alpha-1 antitrypsin (A1AT) deficiency, viral hepatitis, celiac disease and thyroid dysfunction.

While this retrospective cohort study by Yodoshi and colleagues has acknowledged limitations related to its retrospective design, it gives us highly relevant information on this topic. The authors found that 19 children (2%) had other conditions (see Figure 1 in the article for details). While fewer than expected, and a smaller proportion than in previous reports, these data give pause for thought. It is reassuring that the frequency of treatable diagnoses in the cohort was low, but we cannot ignore these results. And looking at the bigger picture framing these results, clearly research into additional best practices for prevention and treatment of NAFLD need to continue.

References

1.  Jenco M. AAP endorses new guidelines on non-alcoholic fatty liver disease. AAP News. Dec 2, 2016. https://www.aappublications.org/news/2016/12/02/FattyLiver120216 Accessed 3/10/21.
2.  Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, Mouzaki M, Sathya P, Schwimmer JB, Sundaram SS, Xanthakos SA. NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):319-334. doi: 10.1097/MPG.0000000000001482. PMID: 28107283; PMCID: PMC5413933.
3.  Shah J, Okubote T, Alkhouri N. Overview of Updated Practice Guidelines for Pediatric Nonalcoholic Fatty Liver Disease. Gastroenterol Hepatol (N Y). 2018;14(7):407-414.