Serum cholesterol esterification in liver disease. Combined determinations of lecithin: cholesterol acyltransferase and lipoprotein-X.

Indireet evidence suggests that lecithin: choles· terol acyltransferase (LCAT) is synthesized in the liver. There are, however, controversial reports in the literature correlating LCAT activity with various forms of liver disease. The purpose of this study was to determine LCAT activity in icteric pa· tients. These were classified not only by the conventional methods, but also with respect to the presence or absence of LP·X, an abnormal plasma lipoprotein, highly specific for demonstrating or exeluding eholestasis. LCAT was measured at different stages of the disease. The patients were divided into 4 groups: 1. Hepatitis with cholestasis (LP.X pos.) [17]; 11. Hepatitis without cholestsis (LP·X neg.) [12]; IIr. Extra· hepatic biliary obstruction (LP·X pos.) (10]; IV. Chronic liver In normal human plasma approximately two thirds of the serum cholesterol is esterified [I]. In patient.s with liver disease, however, the percentage of choles· terol wh ich is esterified may vary to a considerable extent and is often lower than in normals. The reason for this altered ratio of esterified to unesterified cholesterol in liver disease is not fully understood. 1t has recently been proposed by several investigators [2-6) that low lecithin: cholesterol acyltransferase (LCAT) activity in plasma may be responsible for this characteristic lipid pattern. In agreement with earlier studies by Turner et al. [7) these authors demonstrated that this serum enzyme which catalyzes the transfer of fatty acids from the ß position of lecithin to the 3·ß-OH group of cholesterol [8,9) is reduced in almost all liver diseases. The question arises, however, whether LCA T alone is responsible for the fall in the ester: free ratio especially in the light of recent findings by several investigators [10-13] who demonstrated an abnormal low density lipoprotein designated lipo. protein-X (LP-X), which can only be detected in plasma of patients with cholestasis [14). It is now weil known that the plasma low density lipoproteins (LDL) in biliary obstruction are characterized almost ex· ciusively by the presence of two immunochemically distinct lipoproteins, lipoprotein.B (LP.B) and lipo· protein-X (LP.X). LP-X has an uniquely high content of unesterified cholesterol and phospholipids and is thereby at least partially responsible for the plasma lipid alterations in obstructive jaundice [12-13]. The immunochemical detection of this abnormal lipoprotein * Dr. H. WengeJer participated in thiB study aB a postdoctoral fellow of the Department of Internal l\Iedicine, University of Heidelberg, Germany. Supported by the Deutsche Forschungsgemeinschaft. failure (LP·X neg.jpos.) [11]. Compared to normal controls [15], patients from group I had low, group Il had normal, group III had normal and group IV had low LCAT activity. In vitra studies clearly excluded the existence of circulating inhibitors of LCAT. From these data it is suggested that the ratio of esterified to unesterified cholesterol in liver disease depends on two factors: LCAT activity and the occurrence of the abnormal lipoprotein-X. Furthermore these results indicate that combined determinations of LCAT and Lp·X may prove to be useful techniques for differentiating intraand extrahepatic cholestasis. Key wort/sc LCAT, LP·X, lipids in liver disease. has been found to be specific for any form of cholestasis [18]. And thus this test proved to be very useful in differential diagnosis of liver disease [14). It seemed reasonable therefore to determine LCA T and LP-X in parallel in patients with various forms of liver disorders. In this study LCA T was assayed in icteric and non-icteric patients who were classified not only by the conventional mcthods and laboratory data but also with respect to the prcsence 01' absence of LP-X. From these results it becomes apparent that the ratio of esterificd to unesterified .cholesterol in liver disease probably depends on two factors: LCA T activity and the occurrence of the abnormal lipoprotein-X. Further· more these results indicate that parallel determinations of LCAT and LP-X may prove useful fm dif· ferentiation between intraand extrahepatic cholestasis. Jlaterials and )Iethods