Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serial studies of plasma lipids and lipoproteins were performed in 4 patients with acute alcoholic liver disease characterized by a massive fatty liver and laboratory evidence of intrahepatic cholestasis. There were striking alterations in the plasma lipoprotein electrophoretic patterns characterized by the absence of alpha- and pre-beta-lipoprotein bands and the presence of a single band of abnormal mobility. These changes were associated with an extreme decrease in plasma lecithin-cholesterol acyltransferase activity, resulting in greatly reduced levels of plasma cholesteryl esters and increased levels of unesterified cholesterol. In 2 patients hypertriglyceridemia and hypercholesterolemia were present, the latter because of an increase in unesterified cholesterol. Lipoproteins were isolated from the plasma by sequential ultracentrifugation at the densities used for separation of normal very low density, low density, and high density lipoproteins; however, the patients' lipoproteins were different from normal in lipid composition and ultrastructure. All of the lipoprotein fractions were decreased in cholesteryl esters and the major lipoprotein was a triglyceride-rich low density lipoprotein. Electron microscopic studies of the low and high density lipoprotein fractions revealed the presence of bilamellar vesicles and stacked discs. All of the changes in lipoprotein composition and ultrastructure gradually returned to normal with clinical improvement. These observations indicate that alcoholic liver injury is associated with profound alterations in lipoprotein composition and metabolism which may be related in part to lecithin-cholesterol acyltransferase deficiency.
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PMID:Abnormal plasma lipoproteins and lecithin-cholesterol acyltransferase deficiency in alcoholic liver disease. 18 10

In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease.
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PMID:Influence of bile acids and free fatty acids on physicochemical properties of LP-X. 20 27

The apolipoprotein A-1 in cholestatic liver diseases was determined by rocket immunoelectrophoresis. A decrease in the serum apo A-1 was generally observed in LP-X positive liver disease, particularly in the patients with extrahepatic biliary obstruction. With reference to LP-X levels and LCAT activity, the results indicated that not only hepatocellular damage but also cholestasis contribute to the decrease of apo A-1 concentration in patients with liver disease.
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PMID:Apolipoprotein A-1 in cholestatic liver diseases. 20 4

Lipoprotein-X (LP-X) is an abnormal lipoprotein characteristic of cholestasis. To assess recent claims that its serum concentration helps differentiate extrahepatic from intrahepatic cholestasis, we studied 42 consecutive LP-X-positive patients. The mean serum LP-X level was higher in 18 patients with extrahepatic obstruction than in 24 with intrahepatic cholestatis, 321 +/- 89 versus 130 +/- 31 SEM mg per dl (P less than 0.05). However, values overlapped in 38 of the 42 cases, and in the other 4 the diagnosis of extrahepatic obstruction was obvious anyway from clinical examination. LP-X concentration gave little more information than did free cholesterol of phospholipid levels, which it closely paralleled (r = 0.89 and 0.81, respectively, P less than 0.01). There was no correlation with standard liver function tests or with activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. Contrary to recent claims, these findings suggest that serum LP-X quantitation has little or no clinical value in distinguishing extrahepatic from intrahepatic cholestasis.
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PMID:Lipoprotein-X levels in extrahepatic versus intrahepatic cholestasis. 20 14

Plasma cholesterol esters are formed within the circulation by lecithin-cholesterol acyltransferase (LCAT), an enzyme produced by the liver. Patients with hepatocellular disease have low plasma LCAT activity. This largely accounts for the decreased levels of cholesterol esters observed in such patients and appears due to impaired hepatic production of the enzyme. In contrast, activity of the LCAT reaction in patients with cholestasis seems variable and is the subject of controversy, largely because the influence of abnormal cholestatic lipoproteins on the reaction requires further clarification.Human liver contains a lysosomal cholesterol ester hydrolase (CEH) which may play an important role in hepatic cholesterol homeostasis. In patients with liver damage there is no concrete evidence of circulating CEH activity, but recent studies show elevated activity of hydrolase within the liver itself in acute hepatitis. Hepatic activity of another lysosomal enzyme, acid phosphatase, is not increased, suggesting that high CEH in hepatitic liver does not simply reflect a general increase in lysosomal enzymes. The pathogenesis and significance of altered CEH activity in liver disease require further study.
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PMID:Studies on cholesterol ester formation and hydrolysis in liver disease: a selective review. 37 22

The behaviour of LCAT was examined in acute viral hepatitis and post-hepatic cirrhosis. In the former case, the enzyme was also investigated during remissions. The influence of cholestasis on LCAT activity was evaluated. Depression was noted in cirrhosis and the acute stage of hepatitis, whereas enhanced values were observed during remissions. Depression of the enzyme by cholestasis is explained in a variety of ways.
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PMID:[The behavior of lecithin cholesterol acyltransferase (LCAT) in acute viral hepatitis and post-hepatitis cirrhosis]. 44 Jun 18

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)
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PMID:Dyslipoproteinaemia of liver disease. 208 7

We describe here a 28-years-male with AIHA and SLE who had lipid and lipoprotein abnormalities during cholestasis induced by PGE1 administration. High free cholesterol level, 792 mg/dl was found in his serum, and markedly elevated, phospholipid level 1,614 mg/dl. But, LCAT activity was within normal range in this case. An agarose gel electrophoresis of lipoproteins showed abnormal bands which were located in slow alpha 2, pre beta and slow beta, and between beta and origin point. Moreover, it was detected formation of Lp-X from serum of the patient. Serum levels of apoprotein B, C-II, C-III, and E were higher, while apoprotein A-I, A-II were very lower than reference value. From these results, it was suspected that the patient might occur transient abnormal lipid metabolism according to the drug induced hepatic injury.
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PMID:[A case of systemic lupus erythematosus showing abnormal lipoproteins due to accompanied drug induced hepatitis]. 232 24

In this review we have endeavored to emphasize the central role of the liver in normal lipoprotein metabolism and to demonstrate how derangements in these metabolic processes can lead to abnormalities characteristic of liver disease. Since changes in the concentration and composition of plasma lipids and lipoproteins occur frequently in liver disease, these findings may be useful in following the clinical course of patients with liver disease of various causes. It should be emphasized that elevated plasma triglycerides and cholesterol are due to underlying defects in lipoprotein metabolism and should not be confused with primary hyperlipidemia. Impaired cholesterol esterification, abnormal lipoprotein electrophoretic patterns and lipoprotein compositional changes, all reflect abnormalities of lipoprotein metabolism that are secondary to hepatocellular injury or cholestasis. These abnormalities are very sensitive indicators of fundamental metabolic defects that are related in part to LCAT and apoprotein activator deficiencies, impaired H-TGL and LPL activity and, perhaps, defective remnant lipoprotein clearance by the liver. Since these abnormalities tend to improve with clinical recovery they have proved to be reliable and sensitive indicators of hepatic function and thus, are useful in the assessment of liver disease.
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PMID:Lipoprotein metabolism in liver disease. 698 38

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P < 0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P < 0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P < 0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.
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PMID:Apolipoprotein and lipid abnormalities in chronic liver failure. 953 35


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