The Many Names of Fatty Liver Disease: Strengths and Limitations of Metabolic (Dysfunction)-Associated Fatty Liver Disease

Fatty liver disease is a broad entity describing a continuum of liver disease with graded severity, from steatosis to steatohepatitis with inflammation to fibrosis to cirrhosis. ¹ Fatty liver disease can occur in patients with normal BMI, but it is much more common in patients with obesity. ² As such, the prevalence of fatty liver disease has doubled in the past two decades in children and adolescents along with the rise in childhood obesity. ³

Fatty liver disease is thought to be the hepatic manifestation of obesity-related metabolic syndrome, and fatty infiltration appreciated on histology is correlated with insulin resistance.^4,5 An international consensus statement published in 2020 first proposed a shift in terminology to use metabolic (dysfunction)-associated fatty liver disease (MAFLD), which highlights the association between fatty liver disease and metabolic syndrome. ³ How we define this disease entity in children is important in the care of children and adolescents with obesity as it impacts diagnostics, therapies, and outcomes.

Fatty infiltration of the liver in the form of free fatty acids gives rise to reactive oxygen species that drive inflammation, hepatocyte apoptosis, and eventual fibrosis. ² Children with obesity and metabolic syndrome are more likely to develop advanced liver fibrosis, which increases the risk of developing cirrhosis and hepatocellular carcinoma in adulthood.^1,3

A strength of the MAFLD criteria is that they unify features of metabolic syndrome and may promote multidisciplinary treatment approaches, rather than focusing on a single affected organ. The new terminology also moves the diagnosis away from one of exclusion to one of inclusion. Nonalcoholic fatty liver disease (NAFLD) is prominently a diagnosis of exclusion and its use of the term “nonalcoholic” carries certain connotations that present challenges when one seeks to diagnose and describe childhood liver disease. ⁶ Pediatric NAFLD is defined as chronic hepatic steatosis in individuals <18 years of age in the absence of other identified chronic liver disease, such as infectious, genetic, metabolic, and toxic causes. ¹

In contrast, the diagnostic criterion for pediatric MAFLD is based on evidence of intrahepatic fat in addition to the presence of one of the three: (1) excess adiposity, (2) prediabetes or type 2 diabetes mellitus, or (3) other evidence of metabolic dysregulation, which includes increased waist circumference, hypertension, and/or unfavorable alterations in cholesterol and triglycerides. ³ As currently proposed, MAFLD may allow for better integration of care between childhood and adulthood, as patients often face a chronic disease course.

The primary limitation of the term MAFLD is that steatosis, either microvesicular or macrovesicular, is a heterogeneous process in pediatrics and requires consideration of other etiologies. Hegarty and colleagues, therefore, propose three subtypes of fatty liver disease: type 1 inherited metabolic disorders, type 2 metabolic dysfunction (MAFLD), and type 3 fatty liver without other identifiable cause. ⁷

Our brief review of the diagnostic criteria for MAFLD illustrates that there are strengths and limitations to its use, and as such we support the ongoing study of its clinical application. We believe that a unified inclusionary diagnosis would improve the care of pediatric patients with obesity and fatty liver disease.