By Dr. Michael Mendoza, Gastroenterology at CHKD
Over the past several years, it has become increasingly clear that metabolic dysfunction–associated steatotic liver disease (MASLD) is not only prevalent in adults, but now represents the most common chronic liver disease in children. As pediatric providers, we are on the front lines of identifying, counseling, and managing this condition—often long before irreversible liver injury develops.
From NAFLD to MASLD: Why the Name Matters
The shift from nonalcoholic fatty liver disease (NAFLD) to MASLD is more than semantic. The updated terminology removes stigmatizing language (“fatty,” “alcoholic”) and more accurately reflects the underlying metabolic pathophysiology. MASLD is now categorized under the broader umbrella of steatotic liver disease, defined by excess hepatic lipid accumulation in the presence of at least one cardiometabolic risk factor.
Importantly, alternative causes of steatosis—such as celiac disease—must still be considered during evaluation.
Epidemiology and Risk Factors
MASLD is not going away. Global prevalence estimates suggest rates approaching 40–50% when all comers are considered. Genetics play a significant role, particularly variants such as PNPLA3, which help explain why some children—especially those from the Indian subcontinent—may develop steatotic liver disease despite having a normal BMI.
Screening and Diagnosis
Current recommendations support screening children aged 10 years and older who are at risk. Alanine aminotransferase (ALT) remains the most sensitive screening tool, but clinicians must remain aware of assay variability and laboratory-specific reference ranges.
The encouraging reality is that MASLD is reversible, particularly when identified early.
The Central Role of Nutrition: Fructose and Added Sugars
A growing body of evidence highlights fructose as a key driver of hepatic inflammation and de novo lipogenesis. Compared with glucose, fructose consumption is associated with increased plasma endotoxin levels and activation of inflammatory cascades.
In practice, the most impactful intervention is often the simplest: eliminating sugar-sweetened beverages.
- Beverages represent the largest single source of added sugars in children’s diets.
- Commonly consumed drinks—juice, soda, energy drinks, and sports beverages—frequently exceed recommended limits in a single serving.
- The American Heart Association recommends that children aged 2–18 consume no more than six teaspoons (25 grams) of added sugar per day.
A practical counseling strategy is visualizing sugar content. When children measure six teaspoons of sugar into a cup, they are often shocked—yet may routinely consume that amount (or more) in one beverage. This contrast can be a powerful educational tool for families.
A simple but effective clinical recommendation is water only—for at least three months. Removing juice and soda alone can dramatically reduce fructose exposure and hepatic fat production.
Lifestyle Modification Remains the Gold Standard
Despite advances in pharmacotherapy, lifestyle modification remains first-line treatment for pediatric MASLD. Weight loss, dietary change, and physical activity are foundational and effective—particularly when implemented early.
GLP-1 Receptor Agonists: Emerging Evidence
At present, there are no FDA-approved medications specifically for pediatric MASLD. However, glucagon-like peptide-1 (GLP-1) receptor agonists are emerging as promising adjunctive therapies.
GLP-1 receptor agonists:
- Increase insulin secretion and inhibit glucagon
- Slow gastric emptying
- Reduce caloric intake
- Improve metabolic regulation
These agents are already widely used in pediatrics for obesity and type 2 diabetes, prompting investigators to examine their impact on liver disease.
A recent single-center retrospective study published in JPGN evaluated children treated with GLP-1 receptor agonists (primarily semaglutide and liraglutide) for non-liver indications. Over an average treatment duration of 13 months, investigators observed:
- ALT reductions of 23 U/L at six months
- Sustained improvement with an 18 U/L reduction by the end of treatment
- Greater ALT improvement in patients with higher baseline values (≥2× ULN)
- Significant improvements in AST, GGT, triglycerides, and HbA1c
- No significant changes in BMI or BMI z-score
Notably, children with type 2 diabetes experienced the greatest benefit—an important finding given their elevated risk of progression to MASH and fibrosis if left untreated.
Key Takeaways for Clinical Practice
- MASLD is the leading cause of chronic liver disease in children
- The disease is driven primarily by de novo lipogenesis, fueled by excess fructose and added sugars
- Lifestyle modification remains the cornerstone of management
- Eliminating sugar-sweetened beverages is one of the most effective interventions
- GLP-1 receptor agonists are a promising adjunct, particularly in children with obesity and type 2 diabetes
- Early identification matters—MASLD is reversible
As high-quality, prospective studies continue to emerge, pharmacologic therapies may soon play a larger role. For now, combining evidence-based lifestyle interventions with thoughtful use of emerging metabolic therapies offers our best opportunity to change the trajectory of liver disease in children.
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