What is Hepatic Steatosis?
Hepatic steatosis is the abnormal accumulation of fat (specifically triacylglycerols) within liver cells (hepatocytes), defined as intrahepatic fat comprising at least 5% of liver weight. 1, 2
Core Definition and Pathophysiology
Hepatic steatosis represents the visible accumulation of lipid droplets within the cytoplasm of hepatocytes, occurring when there is an imbalance between fatty acid delivery/synthesis and their disposal through oxidation or secretion. 3, 4
The condition develops through four primary mechanisms: 5, 3
- Increased fatty acid influx from adipose tissue and intestinal chylomicrons directly to the liver 3
- Enhanced lipid synthesis through alcohol-induced increases in NADH, triglycerides, and fatty acid production, combined with suppression of mitochondrial β-oxidation 5, 3
- Metabolic dysregulation via ethanol-mediated suppression of AMPK activation, leading to increased lipid biosynthesis through SREBP1c activation and decreased lipolysis through PPARα suppression 5, 3
- Impaired clearance due to acetaldehyde-induced mitochondrial and microtubule damage, resulting in decreased NADH oxidation and VLDL accumulation 5, 3
Histologic Patterns
Two distinct microscopic patterns exist with different clinical implications: 3
- Macrovescicular steatosis involves large lipid droplets occupying the entire hepatocyte cytoplasm, characteristically associated with alcohol, obesity, and diabetes, and carries greater risk for disease progression 3
- Microvescicular steatosis consists of tiny lipid droplets (<1 mm) creating a foamy cytoplasmic appearance, associated with drug toxicity, acute fatty liver of pregnancy, and Reye syndrome, typically without significant impact on organ function 3
Clinical Spectrum and Prevalence
Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) affects 20-30% of the general population, increasing to 70% in obesity and 90% in diabetes. 1
The disease exists along a spectrum: 1, 3
- Simple steatosis (70-75% of cases) represents hepatic fat accumulation without hepatocellular injury or inflammation, remaining benign in most patients with very slow or absent histological progression 1, 3
- Steatohepatitis (25-30% of cases) features hepatocyte injury, ballooning, and inflammation with or without fibrosis, representing a critical pathophysiologic transition that can progress to cirrhosis and hepatocellular carcinoma 1, 3
Clinical Presentation
A critical pitfall: 60-80% of patients with chronic hepatic steatosis remain completely asymptomatic because simple steatosis occurs without cellular injury or inflammation. 3, 6
When symptoms occur, they are nonspecific and may include abdominal discomfort, fatigue, nausea, and muscle pain. 6 The liver capsule lacks pain receptors for stretch or fat accumulation alone; pain typically requires inflammation, rapid enlargement, or capsular distension from other causes. 6
Diagnostic Approach
Ultrasound serves as the first-line investigation, showing increased liver echogenicity compared to renal cortex, with sensitivity of 84.8% and specificity of 93.6% for moderate to severe hepatic fat deposition. 1
Initial evaluation should include: 1
- Liver biochemistries (AST:ALT ratio helps differentiate causes) 1
- Exclusion of other liver diseases 1
- Assessment of metabolic risk factors including obesity, type 2 diabetes, and dyslipidemia 3
Clinical Significance
Hepatic steatosis compromises hepatic microcirculation regardless of underlying etiology. 7 Fatty accumulation increases hepatocyte volume, reducing hepatic sinusoid space by 50% compared to normal liver, potentially resulting in partial or complete obstruction. 7 This impaired microcirculation reduces hepatocyte tolerance against ischemia-reperfusion injury. 7
The presence and progression of liver fibrosis driven by hepatic inflammation is the main predictor of liver-related death across the entire spectrum of steatotic liver diseases. 8