Intrahepatic Cholestasis

Definition

Intrahepatic cholestasis refers to impaired bile formation or flow within the liver, leading to accumulation of bile acids in the liver and bloodstream. It can be caused by liver disease, medications, pregnancy, or genetic disorders.

Epidemiology

• Can occur at any age, more common in adults
• Pregnancy-related intrahepatic cholestasis (ICP) occurs in 0.5–2% of pregnancies, higher in certain populations (South America, Scandinavia)
• More common in women, especially during pregnancy
• Drug-induced or idiopathic forms reported worldwide
• Incidence depends on underlying etiology: viral hepatitis, cholestatic liver diseases, or genetic mutations

Etiology

• Pregnancy-related: hormonal changes (estrogen, progesterone) in the third trimester
• Genetic disorders: mutations in ABCB11, ATP8B1, TJP2 causing familial cholestasis
• Liver diseases: hepatitis, primary biliary cholangitis, primary sclerosing cholangitis
• Drug-induced: anabolic steroids, certain antibiotics, oral contraceptives
• Metabolic disorders: bile acid synthesis defects

Pathophysiology

• Impaired bile formation or excretion within hepatocytes or bile canaliculi
• Accumulation of bile acids in hepatocytes causes cellular injury and inflammation
• Bile acids spill into systemic circulation, causing pruritus and biochemical cholestasis
• In pregnancy, hormonal effects reduce bile flow and alter transporter expression
• Chronic cholestasis can lead to fibrosis and progressive liver injury