What is hepatic steatosis?

Hepatic Steatosis: Definition, Diagnosis, and Clinical Significance

Hepatic steatosis is the accumulation of excess fat in liver cells (hepatocytes), defined as fat content exceeding 5% of liver weight, which can progress from simple fatty liver to inflammation, fibrosis, and cirrhosis if left untreated. 1

Definition and Classification

Hepatic steatosis (fatty liver) is characterized by:

• Accumulation of triglycerides within the cytoplasm of hepatocytes 2
• Requires ≥5% fat content in the liver to meet diagnostic criteria 1
• Can be classified based on etiology:
  • Metabolic Associated Steatotic Liver Disease (MASLD) - formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD) 3
  • Alcohol-related liver disease (ALD)
  • MetALD - overlap between metabolic and alcohol-related causes 4
  • Other rare causes (medications, genetic disorders, viral hepatitis) 5

Histological Classification

Hepatic steatosis can be further categorized by:

1. Pattern of fat accumulation:

   • Macrovesicular steatosis: Large fat droplets that may occupy the entire cytoplasm
     • Associated with alcohol, obesity, and diabetes
     • Severity graded as mild (10-30%), moderate (30-60%), or severe (>60%) 1
   • Microvesicular steatosis: Tiny lipid droplets (<1mm) giving a foamy appearance
     • Associated with drug toxicity, acute fatty liver in pregnancy, and Reye disease 1

2. Presence of inflammation:

   • Simple steatosis (MASL): Fat accumulation without significant inflammation
   • Steatohepatitis (MASH): Fat accumulation with inflammation and hepatocyte injury (ballooning) 1, 3

Clinical Significance

Hepatic steatosis is not a benign condition:

• Affects approximately 30% of the global population 4
• Most common liver disease in developed countries (20-30% prevalence) 1
• Prevalence increases to 70% in obesity and 90% in diabetes mellitus 1
• Can progress to:
  • Inflammation (steatohepatitis)
  • Fibrosis
  • Cirrhosis
  • Hepatocellular carcinoma 1, 6
• Associated with increased mortality and morbidity 6
• Impairs hepatic microcirculation, reducing blood flow by up to 50% 2
• Reduces tolerance to ischemia-reperfusion injury (important in liver transplantation) 2

Diagnostic Approaches

Imaging Methods

1. Ultrasound (US):

   • First-line investigation tool for suspected hepatic steatosis
   • Findings: Increased liver echogenicity compared to renal cortex
   • Grading:
     • Mild: Increased echogenicity with clear visualization of diaphragm and vessels
     • Moderate: Increased echogenicity with obscuration of diaphragm and vessels
     • Severe: Marked increase in echogenicity with non-visualization of diaphragm and vessels 1
   • Sensitivity/Specificity:
     • 84.8% sensitivity and 93.6% specificity for moderate-severe steatosis (>30%)
     • Only 53.3-65% sensitivity for mild steatosis 1

2. Advanced Imaging:

   • Elastography techniques can help assess associated fibrosis
   • MRI-based techniques provide more accurate quantification of fat content 1

Laboratory Assessment

• Elevated aminotransferases (ALT, AST) may be present
• AST:ALT ratio <1 suggests metabolic-related steatosis
• AST:ALT ratio >2 suggests alcohol-related steatosis 1
• FIB-4 index and other non-invasive tests can help assess fibrosis risk 3

Liver Biopsy

• Gold standard for definitive diagnosis of steatohepatitis
• Necessary to distinguish simple steatosis from steatohepatitis
• Allows assessment of inflammation and fibrosis 3

Common Causes

1. Metabolic factors:

   • Obesity
   • Type 2 diabetes
   • Insulin resistance
   • Metabolic syndrome 1, 3

2. Alcohol consumption:

   • Significant cause of hepatic steatosis
   • Diagnosis of MASLD requires alcohol consumption <20g/day (women) or <30g/day (men) 3

3. Other causes:

   • Medications (e.g., corticosteroids, tamoxifen)
   • Genetic disorders
   • Viral hepatitis (especially HCV)
   • Toxin exposure 5, 6

Clinical Implications

• Hepatic steatosis increases risk of liver-related mortality 6
• Presence of fibrosis is the main predictor of liver-related death 4
• In liver transplantation:
  • Mild macrosteatosis (<30%) is generally acceptable for transplantation
  • Moderate steatosis (30-60%) may be used in select cases
  • Severe steatosis (>60%) carries unacceptable risks of graft failure 1
• Steatosis in HCV patients impacts both fibrosis progression and treatment response 6

Hepatic steatosis should be viewed as a potentially serious condition requiring proper diagnosis, monitoring, and management to prevent progression to more severe liver disease.