Is hepatic steatosis a form of fatty liver disease?

Hepatic Steatosis is a Form of Fatty Liver Disease

Yes, hepatic steatosis is a form of fatty liver disease, characterized by the abnormal accumulation of triglycerides within the cytoplasm of hepatocytes. 1

Understanding Hepatic Steatosis

Hepatic steatosis refers to the accumulation of fat in liver cells and is the defining histological feature of fatty liver disease. It is diagnosed when:

• Fat accumulation is present in >5% of hepatocytes based on histological analysis 1
• Or when proton density fat fraction is >5.6% as measured by magnetic resonance techniques 1

Fatty liver disease is broadly categorized into two main types:

1. Nonalcoholic Fatty Liver Disease (NAFLD) - recently renamed as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

   • Requires evidence of hepatic steatosis (by imaging or histology) 1
   • Absence of significant alcohol consumption (defined as <30g/day for men and <20g/day for women) 1
   • Associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia 1

2. Alcoholic Liver Disease (ALD)

   • Hepatic steatosis resulting from excessive alcohol consumption 1
   • Often has an AST:ALT ratio >2 (compared to <1 in metabolic-related fatty liver) 1

Spectrum of Fatty Liver Disease

Fatty liver disease represents a spectrum of conditions with increasing severity:

• Simple Steatosis (NAFL/MASL): Presence of hepatic steatosis without evidence of hepatocellular injury 1

  • Generally has slow, if any, histological progression 1
  • Seen in 70-75% of NAFLD cases 1

• Steatohepatitis (NASH/MASH): Hepatic steatosis with inflammation and hepatocyte injury (ballooning) 1

  • Can progress to fibrosis and cirrhosis 1
  • Seen in 25-30% of NAFLD cases 1

• Advanced Disease: Fibrosis, cirrhosis, and hepatocellular carcinoma 1

Prevalence and Impact

• NAFLD/MASLD affects approximately 30% of the global population 2
• Prevalence increases to 70% in obesity and 90% in diabetes mellitus 1
• Fatty liver disease has become the leading cause of cirrhosis in the EU and USA 2
• Liver fibrosis is the main predictor of liver-related death across the spectrum of steatotic liver diseases 2

Causes of Hepatic Steatosis

Hepatic steatosis can occur in various conditions:

• Primary causes:

  • Metabolic dysfunction (obesity, diabetes, insulin resistance) 1
  • Excessive alcohol consumption 1

• Secondary causes 1:

  • Hepatitis C (especially genotype 3)
  • Wilson's disease
  • Lipodystrophy
  • Starvation
  • Parenteral nutrition
  • Medications (amiodarone, methotrexate, tamoxifen, corticosteroids, valproate)
  • Pregnancy-related conditions (acute fatty liver of pregnancy, HELLP syndrome)
  • Inborn errors of metabolism

Diagnostic Approaches

Hepatic steatosis can be diagnosed through:

• Liver biopsy: The gold standard but invasive with potential risks 1

  • Can identify steatohepatitis and stage fibrosis
  • Provides comprehensive information at cellular level

• Imaging techniques:

  • Ultrasound: Can diagnose moderate-severe hepatic steatosis (>33% fat) with 84.8% sensitivity and 93.6% specificity 1

    • Sensitivity drops to 53.3-65% when including mild steatosis 1
    • Not recommended for diagnosis or grading in children 1

  • MRI/MRS: More accurate quantification of liver fat 3, 4

    • Can measure proton density fat-fraction, a direct measure of liver fat content 4
    • Promising but insufficient evidence for routine use in children 1

Clinical Implications

• Hepatic steatosis is a cardiometabolic risk factor that can contribute to diabetes mellitus and heart disease 1
• It can serve as a co-factor that affects severity and progression of other liver diseases 5
• Persistent steatosis can impair liver viability and function 6
• The presence and progression of liver fibrosis is the main predictor of liver-related mortality 2

Management Approach

Management focuses on:

• Lifestyle modification including weight loss, dietary changes, physical exercise, and limiting alcohol consumption 1
• Optimal management of comorbidities 1
• For those with MASH and significant fibrosis, targeted pharmacotherapies may be considered where approved 1
• Surveillance for complications in advanced disease 1