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Dyslipoproteinaemia of liver disease
Insights
Hepatic diseases cause abnormal lipoprotein levels and composition, particularly in cholestatic conditions, leading to unique lipid profiles like LP-X. These changes offer insights into liver disease mechanisms and lipid metabolism.
Area of Science:
- Biochemistry
- Hepatology
- Lipidology
Background:
- Hepatic diseases significantly alter circulating lipoproteins, affecting their quantity, composition, and structure.
- Dyslipidaemia in liver disease is distinct from other causes, often involving abnormal lipoprotein appearance and electrophoretic mobility.
Purpose of the Study:
- To detail the specific lipoprotein abnormalities observed in various hepatic diseases, with a focus on cholestatic conditions.
- To differentiate lipoprotein profiles in cholestasis from other liver diseases and familial LCAT deficiency.
Main Methods:
- Analysis of lipoprotein composition, electrophoretic mobility, and ultracentrifugal properties.
- Electron microscopy to characterize abnormal lipoprotein structures like LP-X and LP-Y.
- Assessment of high-density lipoprotein (HDL) and its apolipoproteins (apoAI, apoAII, apoE).
Main Results:
- Cholestatic liver disease is characterized by extreme hyperlipidaemia, elevated free cholesterol and phospholipids, and the presence of abnormal lipoprotein-X (LP-X).
- LP-X, a vesicular LDL, is nearly specific to cholestasis and familial lecithin-cholesterol acyltransferase (LCAT) deficiency.
- HDL in cholestasis can present as discoidal particles, and in extrahepatic obstruction, HDL and apolipoprotein levels are often reduced, while intrahepatic cholestasis may show increased HDL2.
Conclusions:
- Lipoprotein abnormalities, including LP-X, LP-Y, and discoidal HDL, are hallmarks of cholestatic liver disease and share similarities with familial LCAT deficiency.
- Acute hepatocellular diseases can present with cholestatic phases exhibiting similar lipoprotein changes.
- Cirrhosis without cholestasis typically shows less severe hyperlipidaemia, reduced cholesterol and apoB, and may lack LP-X despite reduced LCAT activity.
Abstract:
Hepatic diseases differ from most other causes of secondary dyslipidaemia in that the circulating lipoproteins are not only present in abnormal amounts but they frequently also have abnormal composition, electrophoretic mobility and appearance. Pre-beta and alpha bands can be absent on electrophoresis in all types of liver disease although material in the VLDL and HDL ranges can be isolated in the ultracentrifuge. Cholestatic liver disease has been the most extensively studied and the hyperlipidaemia can be extreme with marked elevations of free cholesterol and phospholipids. This results largely from the presence of LP-X, an abnormal LDL, with a vesicular structure that appears in rouleaux formation under the electron microscope. It is virtually specific for cholestasis and familial LCAT deficiency. The LDL, however, is heterogeneous and may also contain a large triglyceride-rich particle (LP-Y) as well as more normal-looking particles, which are none the less depleted in cholesteryl esters and rich in triglycerides. Indeed, when patients with cholestasis are hypertriglyceridaemic the excess triglyceride is to be found predominantly in these two LDL fractions rather than in VLDL. HDL in cholestasis may contain disc-like particles, similar to those newly secreted by the liver and intestine, as well as more normal-looking spherical particles. In extrahepatic obstruction concentrations of HDL and its major apolipoproteins, apoAI and apoAII, are frequently reduced, although a subfraction rich in apoE is often found. In all but the latest stages of chronic intrahepatic cholestasis due to primary biliary cirrhosis, however, HDL, especially HDL2, concentrations are increased, probably due to the presence of a circulating inhibitor of HL. Many of these lipoprotein changes found in cholestasis resemble those of familial LCAT deficiency, although the hyperlipidaemia is not usually so severe in the latter condition. Indeed, in patients with cholestasis but well-preserved LCAT activity many of the characteristic lipoprotein changes, such as LP-X, LP-Y and discoidal HDL, may not be seen. In acute hepatocellular disease, such as alcoholic or viral hepatitis, it is not unusual for the patient to go through a cholestatic phase and many of the same lipoprotein changes may be seen. In cirrhosis without cholestasis the patients are not usually significantly hyperlipidaemic and in advanced cases cholesterol and apoB levels may be reduced. Although LCAT activity and the proportion of plasma cholesterol esterified may also be markedly reduced, LP-X is not usually seen, possibly because the flux of free cholesterol and phospholipid (lecithin), the LCAT substrates, is relatively low. Discoidal HDLs are often present.(ABSTRACT TRUNCATED AT 400 WORDS)