What is hepatic steatosis (fatty liver disease)?

What is Hepatic Steatosis?

Hepatic steatosis is the excessive accumulation of triglycerides within hepatocytes, defined as intrahepatic fat comprising ≥5% of liver weight by histology or >5.6% proton density fat fraction by magnetic resonance spectroscopy. 1

Pathophysiologic Definition

Hepatic steatosis represents the hallmark feature of metabolic dysfunction-associated steatotic liver disease (MASLD), which has replaced the older term non-alcoholic fatty liver disease (NAFLD). 1 The condition is characterized by:

• Fat accumulation mechanism: Triglyceride storage results from multiple metabolic derangements including enhanced influx of free fatty acids from adipose tissue lipolysis, increased de novo lipogenesis in the liver, and reduced clearance through β-oxidation or very-low-density lipoprotein secretion. 2, 3

• Metabolic context: Insulin resistance serves as the central metabolic driver linking adipose tissue dysfunction to hepatic fat accumulation, with strong associations to metabolic syndrome components including abdominal obesity, diabetes, hypertension, and dyslipidemia. 2

Disease Spectrum and Clinical Significance

Hepatic steatosis exists along a spectrum with dramatically different prognoses:

Simple Steatosis (MASL)

• Represents 70-75% of all MASLD cases and involves ≥5% hepatic steatosis without evidence of hepatocellular injury or inflammation. 4, 2
• Carries minimal risk of progression to cirrhosis and may remain benign without cellular insult. 4, 2
• The majority (60-80%) of patients remain completely asymptomatic because the liver capsule lacks pain receptors for stretch or fat accumulation alone. 5, 2

Steatohepatitis (MASH/NASH)

• Occurs in 25-30% of MASLD cases and represents a critical pathophysiologic transition characterized by ≥5% hepatic steatosis plus inflammation with hepatocyte injury (hepatocellular ballooning and lobular inflammation). 5, 4, 2
• Carries substantially higher risk of progression to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. 2, 6
• May produce more symptoms than simple steatosis due to active inflammation. 5

Epidemiology and Risk Factors

The prevalence of MASLD has reached epidemic proportions:

• 20-30% in the general population, increasing to 70% in obesity and 90% in diabetes. 4
• Strongly associated with obesity, type 2 diabetes, and metabolic syndrome, making it the most common chronic liver disease worldwide. 1, 6

Diagnostic Criteria

The diagnosis requires both positive evidence and exclusion criteria:

• Positive evidence: Demonstration of hepatic steatosis by imaging (ultrasound showing increased liver echogenicity compared to renal cortex with 84.8% sensitivity and 93.6% specificity for moderate-to-severe fat) or histology showing ≥5% fat accumulation. 4, 2

• Exclusion criteria: Must exclude secondary causes including significant alcohol consumption (≥30 g/day for men, ≥20 g/day for women), long-term steatogenic medications, viral hepatitis, and other specific liver diseases. 1, 2

Histologic Pattern

• Macrovesicular steatosis is the characteristic pattern, involving large lipid droplets that displace the nucleus and occupy the entire hepatocyte cytoplasm, typically associated with metabolic dysfunction, obesity, and diabetes. 2

Clinical Presentation

Most patients present asymptomatically, but when symptoms occur they are nonspecific:

• Abdominal discomfort, fatigue, nausea, and muscle pain may be reported. 5
• Pain typically requires inflammation (as in steatohepatitis), rapid enlargement, or complications such as progressive fibrosis, cirrhosis, or hepatocellular carcinoma. 5