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The effect of heparin on serum lipoprotein-X.

Serum lipoprotein-X was investigated in 12 patients with cholestasis in basal conditions and 20 minutes after intravenous heparin. In all cases, lipoprotein-X was positive in the first sample and became negative after heparin. A decrease in triglycerides was observed in all patients after heparin with an increase in free fatty acids and mobilization of prebetalipoproteins, and a transformation of lecithin into lysoleithin in 4 cases after heparin. These facts suggest that heparin plays an important role in the mobilization of serum lipoprotein-X.

Adult

Lipoprotein-X and diagnosis of cholestasis: comparison with other biochemical parameters and liver biopsy.

The presence or absence of histological signs of cholestasis (on the basis of liver specimens obtained by means of liver biopsy) was compared with total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, ornithine carbamoyltransferase, serum glutamic oxaloacetic transaminase levels and LP-X test in 157 patients suffering from different liver diseases. The LP-X test was positive in 93% of the 59 cases in whom histological evidence of cholestasis was observed and negative 95% of the 98 cases in whom histological examination was negative. LP-X concurs more frequently with the histological picture than do total bilirubin and alkaline phosphatase. These data confirm that LP-X test is more specific than the tests traditionally used to demonstrate or exclude cholestasis. An increment in gamma-GT levels was observed in 97% of the patients with a positive LP-X test. These clinical results have been discussed in the light of recent data regarding the mechanism of lipoprotein-X formation and the possible relationships between LP-X and gamma-glutamyl transpeptidase.

Adolescent

Quantitative changes of serum lipoprotein-X after cholestyramine administration in infants with cholestatic biliary tract and liver disease.

Lipoprotein-X (LP-X) was determined before and after the administration of cholestyramine in fifty-five infants with persistent cholestatic jaundice to differentiate between intra- and extrahepatic disease. In twenty-seven infants with biliary atresia, serum LP-X prior to cholestyramine ranged from 0.87 to 11.42 g/l (mean: 3.43 g/l; the average concentration was significantly lower (P less than 0.001) in males. After cholestyramine, LP-X rose in twenty-three, remained the same in two, and decreased slightly in two infants. Serum LP-X was present in twenty of the twenty-eight infants with intrahepatic cholestasis prior to cholestyramine in concentrations from 0.84 to 14.19 g/l (mean: 3.13 g/l). After cholestyramine, LP-X decreased in all by an average of 78% (P less than 0.005). The other eight infants did not have LP-X before or after cholestyramine. This study shows that LP-X in the serum of infants with cholestatic jaundice indicates severe cholestasis, but is not itself diagnostic of biliary atresia. The differentiation of biliary atresia from other diseases is readily achieved, as the administration of cholestyramine for 2-3 weeks causes a marked decrease of serum LP-X in patients with patent extrahepatic bile ducts. The absence of serum LP-X excludes biliary atresia.

Bile Ducts, Intrahepatic

Lipoprotein-X and other tests in the diagnosis of obstructive jaundice in the infant.

The infant with elevated direct-reacting bilirubin levels requires an early specific diagnosis to identify those who would require early surgical intervention and those in whom the bilirubin levels will eventually return to normal. This study compares the accuracy of three tests: the serum lipoprotein-X (LP-X), the I131 rose bengal (IRB) excretion and the serum alpha-fetoprotein (AFP) in making a specific diagnosis in 15 patients. When used individually the accuracy of the tests varies from 56-100%. The LP-X and IRB excretion are more specific and when in agreement are 100% acurate in the diagnosis of the neonatal hepatitis syndrome (NHS) or extrahepatic biliary obstruction (EHBO). This study suggests that both the LP-X and IRB excretion should be used in the investigation of the infant with conjugated hyperbilirubinemia.

Biliary Tract Diseases

On the metabolism of lipoprotein-X (LP-X).

The characteristic low-density lipoprotein of cholestasis (LP-X) earlier described for humans is found with identical properties in dogs and rats after experimental cholestasis. After ligation of the common bile duct, LP-X may be detected in the plasma within the first 20 hours. A period of marked increase in concentration is followed by decreasing plasma concentrations and LP-X becomes undetectable 7-10 days after ligation of the bile duct in rats. High plasma bile salt concentration may alter the structural integrity of LP-X and may in part be responsible for its disappearance after long-lasting and severe biliary obstruction. Plasma decay curves for isolated LP-X injected intravenously into healthy animals revealed a rapid early fall in concentration followed by a gradual decline. The calculated fractional catabolic rate of LP-X was found to be 0.450 +/- 0.069 for dogs and 1.553 +/- 0.096 for rats corresponding to a mean biological half life of 37.7 +/- 6.4 h or 10.7 +/- 0.6 h, respectively. In vitro LP-X degradation occurs in post-heparin plasma, however, it seems to be too early to speculate on the enzyme activity and on the mode of action responsible for this disappearance.

Animals

Diagnostic importance of lipoprotein-X (LP-X) in the diagnosis of cholestasis.

In 317 patients with diseases of the liver and bile tract the authors determined LP-X in the serum and the obtained results were compared with the morphological findings in liver tissue or intraoperative examination of the extrahepatic bile ducts. Int he same patients serum bilirubin, total cholesterol, alkaline phosphatase activity, gamma-glutamyltranspeptidase and leucylaminopeptidase activity were determined. In the light of these results the authors believe that detection of LP-X in the serum is a sensitive and specific method in the diagnosis of cholestasis and that it is of greater usefulness than determination of alkaline phosphatase activity. Determinations of other biochemical parameters is of small diagnostic importance in these cases.

Adolescent

Studies in cholestasis of pregnancy.

Forty-one pregnant women with pruritus, in whom cholestasis was verified by the presence in their serum of an abnormal lipoprotein, lipoprotein-X (LP-X), were divided into two clinical groups, pruritus gravidarum (PG) (n=20) and hepatosis of pregnancy (HP) (n=21) in relation to serum bilirubin (below and above 1.2 mg/100 ml, respectively) and/or SGOT, SGPT (below and above 50 units/l, respectively). In HP, but not in PG, serum lipids, i.e. cholesterol, phospholipids, triglycerides, pre-beta-lipoproteins (very-low-density lipoproteins), and low-density lipoproteins were increased and high-density lipoproteins decreased when compared with suitable controls. Serum lipids were elevated in proportion to the derangement in the liver function tests, alkaline phosphatase, SGOT, and SGPT. The occurrence of LP-X was inversely related to HDL cholesterol, suggesting a causal relationship between HDL lipid metabolism and the presence of LP-X. Serum TIBC, Simplastin A, and serum iron were elevated in HP in relation to the degree of deterioration of liver function tests. Some of these changes in serum in cholestatic pregnancy may partially (serum triglycerides and pre-beta-lipoproteins) or completely (TIBC and Simplastin A) be explained by an enhanced estrogen influence in promoting increased liver lipid/protein metabolism.

Alanine Transaminase

Abnormal lipoprotein appearing in plasma of patients who received a ten percent soybean oil emulsion infusion.

In 42 of 43 surgical patients who received a 10% soybeam oil emulsion (Intralipid), abnormal lipoprotein was detected in their plasma 1 to 2 days after the initial Intralipid infusion. This abnormal lipoprotein was proven to appear as a result of the infusion of soybean oil emulsion regardless of the patient's original diseases, age, sex, liver function, or concomitantly administered solutions. In addition, this abnormal -ipoprotein was found to have various similarities to lipoprotein-X (LP-X) which is found in plasma from patients with obstructive jaundice or familial lecithin:cholesterol acyltransferase deficiency. Therefore, this abnormal lipoprotein was tentatively named LP-X--like substance (LP-X-LS). A comparison of the properties of LP-X and LP-X-LS was performed and the following results were obtained: (1) LP-X-LS migrated toward the cathode on Bacto-Agar gel electrophoresis similarly to LP-X; (2) the stability of LP-X and LP-X-LS against heating and freezing were almost equal under various conditions; (3) LP-X-LS could be absorbed by anti--LP-X serum; (4) LP-X-LS existed in low density fraction (d = 1.063) separated by ultracentrifugation from plasma; (5) electron microscopic study of low-density lipoprotein particles from LP-X-LS positive plasma revealed that LP-X-LS had a similar ultrastructure to LP-X. From these results it is suggested that LP-X-LS is an abnormal lipoprotein quite similar to LP-X.

Adult

[Lipoprotein X in hepatobiliary diseases].

The diagnostic and prognostic reliability of lipoprotein-X (Lp-X) in demonstrating or ruling out cholestasis has been evaluated in a group of 80 patients with diseases of the liver and/or the biliary tracts, and in 103 subjects with various other diseases. The results of Lp-X detection were compared with the so-called "enzymes indicating cholestasis": alkaline phosphatase, leucine arylamidase, and gamma-glutamyltranspeptidase. Where possible a histologic specimen of the liver was obtained. The correlation between Lp-X and "enzymes indicating cholestasis" was satisfactory in more than 90% of cases. When compared with the histologic findings, Lp-X proved to be more reliable than the enzymes. Despite this fact, Lp-X did not show absolute specifity in the detection of cholestasis as there were several negative results in cases with histologically proven cholestasis. Furthermore, the differentiation of intra- and extrahepatic cholestasis was not possible on the basis of Lp-X. In the control group of 103 patients with other than hepatobiliary diseases, a positive Lp-X result was found in 3 cases. Further investigations in these three patients revealed that primarily unsuspected hepatobiliary disease could not be ruled out. In the follow-up of a hepatobiliary disease the transition of Lp-X to negative indicates a trend towards improvement of cholestasis 1-2 weeks earlier than the enzymes mentioned above.

Alkaline Phosphatase

[LP-X in newborns: increased incidence of positive tests without cholestasis (author's transl)].

The investigation of 194 newborns has shown that during the first weeks of life the abnormal lipoprotein-X (LP-X) was present in the serum of nearly 50% of the infants, with no clinical chemical evidence of cholestasis. The percentage of LP-X positive tests was even higher in the group of immature newborns (65%). There was no correlation between the bilirubin concentration and the detection of LP-X. The activities of leucine arylamidase (EC 3.4.1.1) and gamma-glutamyltransferase (EC 2.3.2.2) as well as the concentrations of total and free cholesterol did not differ in the LP-X positive and negative infants. Except in one case, LP-X was never detectable on the first day of life. The earliest date of appearance was the second day. In the serum of some infants, who were LP-X positive shortly after birth, the lipoprotein could still be found at the age of 2--3 months. The incidence of LP-X was not higher in newborns with blood group incompatibility than in newborns with unspecific hyperbilirubinaemia. After exchange transfusions LP-X disappeared in most cases, but it could later often be detected again. In some newborns, who were LP-X negative a few days after birth LP-X was first detected at the age of 2-3 months. The LP-X test is of no use for th diagnosis of cholestasis in newborn infants. The test is specific for cholestasis only after the first year of life. The increased incidence of positive LP-X tests in newborns is discussed as a consequence of immature liver function.

Bilirubin

Determination of cryoglobulins as lipoprotein-autoantibody immune complexes and antigenic determinants against antilipoprotein autoantibody.

Serum IgG-antilipoprotein-autoantibody activity (at 4 degrees C) of a plane xanthoma patient was shown by double-immunodiffusion method. Cryoglobulins in the serum were dissociated to polyclonal IgG and alpha- and beta-lipoproteins by acidification and were reconstructed by neutralization. IgG fraction of the cryoglobulins precipitated with lipoproteins. The cryoglobulins were thus demonstrated to be immune complexes of polyclonal IgG-antilipoprotein-autoantibody and both alpha- and beta-lipoproteins. A part of the lipoprotein-autoantibody immune complexes was not cryoprecipitable. Antigenic determinants for the autoantibody existed in the lipid moieties of lipoproteins, in contrast to the apoproteins which determined the specificity to heteroimmune antilipoprotein antibody. The presence of more than nine different antigenic determinants against the autoantibody indicated that lipoproteins were immunologically heterogeneous depending upon the lipid moieties. Lipoproteins reactive with the autoantibody varied quantitatively in normal individuals and were not detected in a primary hyper-beta-lipoproteinaemia patient and in a primary biliary liver cirrhosis patient with much lipoprotein-X. The absence of antigenicity in the two patients' sera is most likely caused by abnormal lipid moieties of lipoproteins.

Adult

[Clinical significance of the combined determination of alpha 1 fetoprotein, lipoprotein X, and hepatitis B antigen and antibodies].

In a four-year prospective study 4000 patients of a gastroenterologic and hematologic department were screened for alpha1-fetoprotein (AFP), lipoprotein-X (LPX), and hepatitis-B antigen and antibody (HBsAg, HBsAb). Only histologically confirmed results were used for the evaluation of this study. Liverscintigraphy using 99m-Tc-S-colloid was performed as the morphological examination. 85% of focal liver diseases were seen as space-occupying lesions in the radioscan. The interpretation of their dignity was performed with success by means of 67-galliumcitrate with an overall diagnostic accuracy of 90%. With the methods, presented in this paper, positive results of AFP-LPX-, HBsAg- and HBsAb-determinations mean, without exception, an informational gain. In 1241 of 4000 patients, 1417 positive results were recorded. In combination with two-step radionuclide-scintigraphy as the morphological element of our screening procedure, focal diseases of the liver are no longer a diagnostic problem. Additional information of diagnostic relevance is expected in about 35% of all diffuse hepatocellular diseases.

Antibodies, Viral