What is hepatic steatosis?

What is Hepatic Steatosis?

Hepatic steatosis is the abnormal accumulation of fat (specifically triglycerides) in the liver, defined as intrahepatic fat comprising at least 5% of liver weight, which can be detected by imaging or histology. 1, 2

Core Definition and Pathophysiology

Hepatic steatosis represents excess lipid accumulation within hepatocyte cytoplasm, resulting from an imbalance between fat acquisition and removal mechanisms. 3, 2 The condition develops through several key pathways:

• Enhanced influx of free fatty acids from adipose tissue and chylomicrons from intestinal mucosa directly to the liver contributes to hepatic triglyceride accumulation in most patients with metabolic dysfunction. 4
• Increased de novo lipogenesis (fat synthesis within the liver itself), reduced β-oxidation (fat burning), and/or decreased very-low-density lipoprotein (VLDL) secretion all contribute to fat retention. 2
• Alcohol-related mechanisms include increased NADH synthesis that drives triglyceride production while suppressing mitochondrial fat oxidation, plus ethanol-mediated suppression of AMPK activation resulting in increased lipid biosynthesis. 4

Histologic Patterns and Clinical Significance

There are two distinct microscopic patterns with different clinical implications:

• Macrovescicular steatosis involves large lipid droplets occupying the entire hepatocyte cytoplasm and is characteristically associated with alcohol, obesity, and diabetes—this pattern carries greater clinical significance for disease progression. 4
• 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—this pattern typically does not preclude organ function. 4

Disease Spectrum and Progression Risk

Hepatic steatosis exists along a clinical spectrum with vastly different prognoses:

• Simple steatosis (NAFL/MASLD without inflammation) represents 70-75% of cases, where patients have hepatic steatosis without hepatocellular injury or ballooning—most remain asymptomatic with very slow or absent histological progression. 4, 5
• Steatohepatitis (NASH/MASH) occurs in 25-30% of cases and represents a critical pathophysiologic transition, characterized by hepatic steatosis plus inflammation with hepatocyte injury (ballooning), with or without fibrosis—these patients can exhibit histological progression to cirrhotic-stage disease. 4, 5
• Advanced disease can progress through fibrosis to cirrhosis, liver failure, and hepatocellular carcinoma, with the presence and progression of liver fibrosis being the main predictor of liver-related death. 1, 6

Metabolic Context and Epidemiology

Hepatic steatosis is intrinsically linked to metabolic dysfunction:

• Prevalence reaches 20-30% in the general population, increasing to 70% in obesity and 90% in diabetes. 4, 5
• Associated conditions include obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome as the primary drivers. 1, 4, 6
• Diverse etiologies include not only metabolic factors but also excess alcohol, medications, genetic disorders, viral hepatitis, and toxins. 3

Critical Clinical Pitfall

The majority (60-80%) of patients with chronic hepatic steatosis remain completely asymptomatic because simple steatosis occurs without cellular injury or inflammation, making early detection challenging and underscoring the importance of screening high-risk populations despite normal liver biochemistries. 4 The condition can significantly impair hepatic microcirculation, with fat accumulation reducing sinusoidal space by 50% compared to normal liver, which compromises tolerance to ischemia-reperfusion injury. 7