What is the role of hyperlipidemia in the pathophysiology of cholestasis?

Updated: Aug 09, 2017
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: Carmen Cuffari, MD  more...
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Answer

Hyperlipidemia is characteristic of some but not all cholestatic diseases. Serum cholesterol is elevated in cholestasis because its metabolic degradation and excretion are impaired. Bile is the normal excretory pathway for cholesterol, and with reduced bile formation, cholesterol is retained. Cholesterol retention can cause an increase in membrane cholesterol content and a reduction in membrane fluidity and membrane function, thereby amplifying the cholestasis. Furthermore, bile salts are the metabolic products of cholesterol, and in cholestasis, synthesis of bile salts is reduced. Much of plasma cholesterol is in the form of lipoprotein-X, an abnormal lipoprotein observed only in the serum of patients with cholestasis.

The contribution of dietary cholesterol to the elevated serum cholesterol in patients with cholestasis is probably minimal, and limiting the diet in order to reduce serum cholesterol is not justified because that maneuver may have secondary effects on nutrition. Furthermore, the use of oral bile salt–binding agents, such as cholestyramine, has little effect on serum cholesterol in this setting. Agents that block the synthesis of cholesterol have been used sparingly in cholestasis and cannot be recommended at this time. The proper approach to treating hypercholesterolemia in cholestatic liver disease is to treat the liver disease itself.


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