What is hepatic steatosis?

Hepatic Steatosis: Definition and Clinical Implications

Hepatic steatosis is defined as the accumulation of excess triglycerides in the liver, specifically when fat content reaches at least 5% of liver weight. 1

Definition and Pathophysiology

• Hepatic steatosis is characterized by abnormal lipid accumulation in the liver, primarily in the form of triglycerides within hepatocytes 1, 2
• The condition is detected when fat comprises at least 5% of the liver's weight, representing the earliest stage in fatty liver disease spectrum 1
• Steatosis occurs through several mechanisms:
  • Increased flux of fatty acids to the liver
  • Enhanced de novo lipogenesis (fat production within the liver)
  • Reduced clearance through β-oxidation
  • Decreased very-low-density lipoprotein (VLDL) secretion 1

Types and Causes

• Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) is the most common form in developed countries, with prevalence of 20-30% in the general population, increasing to 70% in obesity and 90% in diabetes 3
• Alcohol-induced steatosis occurs through multiple mechanisms:
  • Alcohol oxidation increases NADH, triglycerides, and fatty acid synthesis while suppressing mitochondrial β-oxidation
  • Increased influx of free fatty acids from adipose tissue and chylomicrons from intestinal mucosa
  • Suppression of AMPK activation leading to increased lipid synthesis and decreased lipolysis
  • Acetaldehyde-induced mitochondrial damage causing decreased NADH oxidation and VLDL accumulation 3
• Other causes include medications, genetic disorders, viral hepatitis, and toxins 4

Diagnostic Features

• Ultrasound is commonly used as first-line investigation, showing increased liver echogenicity compared to renal cortex 5
• Grading of steatosis by ultrasound:
  • Mild: Mild diffuse increase in liver echogenicity with clear visualization of diaphragm and intrahepatic vessel walls
  • Moderate: Increased echogenicity with slightly impaired visualization of intrahepatic vessels and diaphragm
  • Severe: Marked increase in echogenicity with poor or non-visualization of intrahepatic vessels, posterior liver portion, and diaphragm 3, 5
• Ultrasound has high sensitivity (84.8%) and specificity (93.6%) for moderate to severe hepatic fat deposition (>30% by histology) but lower accuracy for mild steatosis 3, 5

Clinical Spectrum and Progression

• Simple hepatic steatosis (70-75% of MASLD cases) may remain benign without cellular insult 3
• Steatohepatitis (MASH, formerly NASH) occurs in 25-30% of cases, featuring hepatocyte injury and inflammation 3
• Progressive inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma 3
• The AST:ALT ratio can help differentiate causes:

  • 2 in alcohol-induced fatty liver disease

  • <1 in metabolic disease-related fatty liver 3

Pathophysiological Consequences

• Hepatic steatosis compromises liver microcirculation regardless of underlying etiology 6
• Fat accumulation increases hepatocyte volume, reducing hepatic sinusoid space by up to 50% compared to normal liver 6
• This can result in partial or complete obstruction of sinusoids, reducing total hepatic blood flow 6
• Impaired microcirculation decreases hepatocyte tolerance to ischemia-reperfusion injury, relevant in liver transplantation 6

Clinical Implications and Management

• Increased liver echogenicity should prompt evaluation for fatty liver disease, especially in patients with risk factors such as obesity, type 2 diabetes, or metabolic syndrome 5
• Initial evaluation includes:
  • Liver biochemistries (ALT, AST)
  • Exclusion of other liver diseases through serological testing
  • Assessment of alcohol intake 5
• Risk stratification for advanced fibrosis using non-invasive tests is recommended 5
• Management focuses on:
  • Lifestyle modifications including weight loss, dietary changes, and physical exercise
  • Optimal management of comorbidities
  • Consideration of incretin-based therapies for type 2 diabetes or obesity
  • Bariatric surgery as an option for those with obesity 3

Important Considerations

• Fatty liver can mask underlying focal lesions due to increased background echogenicity 5
• Ultrasound assessment should be standardized using the hepatorenal index for more objective evaluation 3, 5
• The presence and progression of liver fibrosis, driven by hepatic inflammation, is the main predictor of liver-related mortality across the spectrum of steatotic liver diseases 2