What is the difference between steatosis and steatohepatitis?

Difference Between Steatosis and Steatohepatitis

Steatosis is characterized by fat accumulation in the liver, while steatohepatitis requires the presence of steatosis plus inflammation and hepatocyte injury (ballooning), with or without fibrosis. 1

Key Distinguishing Features

Steatosis

• Definition: Presence of fat accumulation in the liver (≥5% hepatic steatosis) 1
• Histological features:
  • Predominantly macrovesicular steatosis 1
  • May occur with or without minimal inflammation 1
  • No evidence of hepatocellular injury/ballooning 1
• Progression risk:
  • Traditionally considered more benign than steatohepatitis 1
  • However, can progress to steatohepatitis in some patients, especially with persistent metabolic risk factors 2

Steatohepatitis

• Definition: Presence of steatosis plus inflammation and hepatocyte injury 1
• Histological features:
  • Steatosis (≥5% hepatic steatosis) 1
  • Inflammation (lobular inflammation with polymorphonuclear neutrophils) 1
  • Hepatocyte ballooning (evidence of cell injury) 1
  • Often associated with (but not required for diagnosis):
    • Mallory-Denk bodies 1
    • Megamitochondria 1
    • Perisinusoidal fibrosis 1
• Pathophysiology:
  • Involves toxic effects of metabolites (like acetaldehyde) 1
  • Production of oxygen free radicals and lipid peroxidation 1
  • Activation of pro-inflammatory cytokines (TNF-α, IL-17) 1
  • Altered gut microbiota and increased intestinal permeability 1

Clinical Significance of the Distinction

1. Disease Progression Risk:

   • Steatohepatitis has a significantly higher risk of progression to fibrosis and cirrhosis 1
   • Steatohepatitis is associated with 40% risk of developing cirrhosis 1
   • Steatosis alone has traditionally been considered more benign, though recent evidence suggests it can progress in some cases 2

2. Mortality Risk:

   • NASH conveys increased overall mortality compared to simple steatosis 3
   • Steatohepatitis is associated with higher liver-related mortality 1

3. Diagnostic Approach:

   • Liver biopsy remains the gold standard for distinguishing between steatosis and steatohepatitis 1
   • Non-invasive tests (imaging, biomarkers) can identify steatosis but cannot reliably distinguish it from steatohepatitis 1

4. Management Implications:

   • Patients with steatohepatitis require closer monitoring and more aggressive intervention 1
   • Steatohepatitis may warrant consideration for clinical trials and emerging therapies 1

Common Pitfalls in Distinguishing the Conditions

1. Relying solely on imaging: Ultrasound, CT, and MRI can detect steatosis but cannot distinguish it from steatohepatitis 1

2. Overreliance on liver enzymes: Normal liver enzymes do not exclude steatohepatitis, and progression from steatosis to steatohepatitis can occur independent of aminotransferase changes 2

3. Assuming steatosis is always benign: Recent evidence suggests that isolated steatosis can progress to steatohepatitis, particularly when metabolic risk factors persist 2

4. Terminology confusion: The term "borderline NASH" is sometimes used when not all diagnostic criteria for steatohepatitis are met, which can lead to diagnostic uncertainty 1

In clinical practice, the distinction between these entities has important prognostic implications, with steatohepatitis representing a more severe condition requiring closer monitoring and more aggressive management of underlying risk factors to prevent progression to cirrhosis and liver-related mortality.