Pediatric Fatty Liver Disease: NIDDK Research Highlights Growing MASLD Epidemic in Children

What Is Pediatric MASLD and Why Is It Increasing?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the new consensus name for what was previously called nonalcoholic fatty liver disease (NAFLD). The terminology change, endorsed in 2023 by the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Latin American Association for the Study of the Liver (ALEH), emphasizes the metabolic drivers of the condition rather than defining it by what it is not. The renaming also aims to reduce stigma and more accurately reflect disease mechanisms.

In children, MASLD has emerged as the most common chronic liver disease in the United States and other high-income countries, with prevalence closely tracking rates of childhood obesity. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has identified pediatric fatty liver disease as a research priority through its support of multi-center studies examining how the disease progresses from simple steatosis to steatohepatitis, fibrosis, and, in a subset of children, cirrhosis — sometimes before adulthood.

How Is Pediatric MASLD Diagnosed and Treated?

There is no single blood test that definitively diagnoses MASLD in children. Clinicians typically evaluate children with obesity or metabolic risk factors who have persistently elevated alanine aminotransferase (ALT), combined with imaging such as ultrasound or, increasingly, noninvasive fibrosis assessment tools like vibration-controlled transient elastography. Liver biopsy remains the reference standard for staging disease severity but is reserved for selected cases. Professional guidelines from NASPGHAN and AAP recommend ALT-based screening in children with obesity starting around ages 9 to 11.

Treatment for pediatric MASLD centers on lifestyle modification: dietary changes that reduce added sugars and ultra-processed foods, increased physical activity, and sustained weight management. The NIDDK-funded TONIC trial, published in JAMA, evaluated vitamin E and metformin in children with biopsy-proven NAFLD and did not find either agent superior to placebo for the primary endpoint, underscoring the continuing gap in pharmacologic options. Resmetirom, the first FDA-approved drug for adult MASH, is not approved for pediatric use, and trials in younger populations will be needed before any therapy can be routinely recommended for children.

What Are the Long-Term Health Consequences for Affected Children?

Long-term follow-up studies suggest that children with MASLD face elevated risks well beyond the liver itself. The condition is strongly associated with insulin resistance, type 2 diabetes, dyslipidemia, and hypertension, and is increasingly recognized as an early marker of cardiometabolic disease. NIDDK-supported cohort research has documented that a subset of children develop advanced fibrosis during adolescence, and rare cases require liver transplantation before age 25.

Because MASLD is often asymptomatic in its early stages, many affected children are identified only incidentally through elevated liver enzymes on routine bloodwork. Public health experts emphasize that prevention — through healthy school food environments, access to physical activity, and family-based behavioral support — remains the most impactful strategy. Ongoing NIDDK research is exploring biomarkers that could better identify children at risk of progression, as well as the role of the gut microbiome and genetic factors such as PNPLA3 variants in driving disease severity.