NAFLD: >5% liver steatosis (fat) in absence of another cause.

Divided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH).

NAFL: simple fat deposition (steatosis) without liver cell injury or fibrosis

NASH: fat deposition with liver cell injury and inflammation +/- fibrosis

Demographics

Very common. In Australia, in 40% adults over 50. More common in men. Should be considered in obese children and adolescents. Expected to rise in coming years.

Aetiology

Genetics, diet, exercise, strong links to metabolic syndrome.

Risk Factors

Type 2 diabetes, age >50, obesity, metabolic syndrome, CVD risks (weight circumference, elevated triglycerides, reduced HDL-cholesterol, elevated blood pressure, elevated fasting glucose)

Pathophysiology

Insulin resistance leads to decreased insulin inhibition of hormone sensitive lipase (HSL) and decreased activity of lipoprotein lipase. Increased HSL and decreased LPL leads to hydrolysis of FFA and decreased uptake of FFA into tissues. This increases FFA in circulation and in V/LDLs. FFAs converted to triglycerides, increasing TG accumulation in hepatocytes and leading to steatosis.

Increased mitochondrial stress from FA oxidation leads to increased inflammatory cytokines, resulting in steatohepatitis. Increased reactive oxygen species (from FA oxidation) activate stellate cells which cause fibrosis through collagen synthesis.

Clinical Features

Hepatomegaly