Plasma lipoprotein composition in alcoholic hepatitis: accumulation of apolipoprotein E-rich high density lipoprotein and preferential reappearance of "light'-HDL during partial recovery.

Abstract

Abnormal lipoproteins accumulate in the plasma of alcoholic hepatitis patients in association with a deficiency of the cholesterol esterifying enzyme, lecithin:cholesterol acyl-transferase. Most of these abnormal lipoproteins are found in the d > 1.006 g/ml density fraction. To investigate the composition and morphology of the lipoproteins at various times during the illness in four patients, we have employed density gradient ultracentrifugation combined with analyses of gradient fractions by polyacrylamide gel electrophoresis, electroimmunoassay, and electron microscopy. At the onset of the illness, plasma cholesteryl esters ranged from 19-34% of total cholesterol; high density lipoprotein (HDL) cholesterol and apoA-I, the major HDL apoprotein, were <10% of normal; and most of the d > 1.006 g/ml triglycerides and phospholipids were found in the LDL density region. A linear correlation (r = 0.964, P < 0.001) was found between the d > 1.006 g/ml apoB concentration and the summation of the triglyceride and esterified cholesterol for that fraction, indicating a constant ratio of apoB to the summation of these two "core lipids". ApoA-I was primarily found in the fraction d > 1.18 g/ml (HDL(3) and VHDL) but not at all in the HDL(2) density range of the gradient. No cholesteryl esters were present in the apoA-I containing fractions. In contrast to normal, large amounts of apoE accumulated in lipoproteins isolated at d 1.055-1.114 g/ml. The apoE-rich fractions contained primarily phospholipids and unesterified cholesterol; they appeared by electron microscopy to be mixtures of spherical particles, vesicular particles, and chains of bilamellar discs. Analyses of the density gradient fractions by SDS polyacrylamide gel electrophoresis under reducing conditions indicated that apoA-II levels and distribution paralleled apoA-I, not apoE, providing evidence against appreciable concentrations of apoE-apoA-II complexes. During partial recovery from alcoholic hepatitis in three patients, the d > 1.006 g/ml unesterified cholesterol and triglyceride levels decreased, while esterified cholesterol, HDL-cholesterol, and apoA-I levels increased. The first HDL fractions to reappear were lipoproteins with HDL(2) density characteristics, as evidenced by simultaneous increases of apoA-I, apoA-II, cholesteryl esters and phospholipids. Lipoproteins with HDL(3) density characteristics appeared later. Long-term (6-10 months) follow-up studies indicated a substantial elevation of HDL cholesterol and apoA-I in three of the four patients that appeared to have resulted from further increases in their HDL(2)-like subspecies. The above results illustrate the diversity of abnormal lipoproteins in alcoholic hepatitis and the ability of density gradient ultra-centrifugation combined with lipid and apolipoprotein quantitation, electron microscopy, and polyacrylamide gel electrophoresis to partially resolve those lipoproteins in the d > 1.006 g/ml plasma fraction.-Weidman, S. W., J. B. Ragland, and S. M. Sabesin. Plasma lipoprotein composition in alcoholic hepatitis: accumulation of apolipoprotein E-rich high density lipoprotein and preferential reappearance of "light"-HDL during partial recovery.