Metabolic Dysfunction-Associated Steatotic Liver Disease

Definition

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is characterized by hepatic steatosis due to metabolic risk factors such as obesity, insulin resistance, and dyslipidemia, in the absence of significant alcohol intake.

Epidemiology

• Global prevalence estimated at 25–30%, higher in patients with obesity and type 2 diabetes
• Increasing prevalence in both adults and children due to rising obesity rates
• More common in males than females in many populations
• Significant regional variation: highest in the Middle East, South America, and Asia
• Progression to NASH (nonalcoholic steatohepatitis) occurs in 20–30% of patients
• MASLD is a leading cause of chronic liver disease and hepatocellular carcinoma in the Western world

Etiology

• Metabolic syndrome components: obesity, insulin resistance, type 2 diabetes, dyslipidemia, hypertension
• Genetic predisposition: PNPLA3, TM6SF2, MBOAT7 polymorphisms
• Medications: corticosteroids, tamoxifen, amiodarone (rare secondary causes)
• Lifestyle factors: sedentary behavior, high-calorie diet, fructose intake
• Exclusion of significant alcohol consumption (<20 g/day for women, <30 g/day for men)

Pathophysiology

• Excess free fatty acids accumulate in hepatocytes due to insulin resistance and altered lipid metabolism
• Hepatic steatosis triggers oxidative stress, mitochondrial dysfunction, and inflammatory pathways
• Cytokine-mediated hepatocyte injury leads to NASH in a subset of patients
• Progressive fibrosis can develop through activation of hepatic stellate cells
• Advanced fibrosis increases risk of cirrhosis, liver failure, and hepatocellular carcinoma