What is the Origin of Intrahepatic Cholestasis?

The term is a combination of intra- (within), hepatic (liver), and cholestasis (stoppage of bile flow, from the Greek chole for bile and stasis for standing). The clinical recognition of drug-induced cholestasis, especially in response to sex steroids, led to the formal classification of this hepatotoxicity. The historical use of high-dose, non-bioidentical oral hormones highlighted the vulnerability of the bile transport system to hormonal influence.

What is the Mechanism of Intrahepatic Cholestasis?

The mechanism involves the interference of exogenous hormones or their metabolites with the critical transport proteins located on the hepatocyte membrane that are responsible for the uptake and efflux of bile acids and bilirubin. Oral estrogen, for instance, can impair the function of the Bile Salt Export Pump (BSEP), a major efflux transporter. This inhibition leads to the retention of bile salts within the hepatocyte, which are themselves detergent-like and cytotoxic at high concentrations. The resulting accumulation causes cellular damage and reduces the driving force for bile secretion, thus inducing the clinical picture of cholestasis.

Intrahepatic Cholestasis

Meaning

Intrahepatic cholestasis is a clinical condition characterized by impaired bile flow due to a functional defect within the liver cells (hepatocytes) or the small bile ducts (canaliculi) inside the liver. This impairment leads to the accumulation of bile acids and bilirubin in the liver and bloodstream, resulting in symptoms such as jaundice and pruritus. In the context of hormonal health, certain exogenous hormones, particularly high-dose oral estrogens and some anabolic steroids, are known to be cholestatic agents that can induce this condition. Careful selection of hormone type and delivery route is necessary to mitigate this hepatobiliary risk.