In vivo evaluation of lipoprotein cholesterol ester metabolism in patients with liver disease.

Fifteen patients with liver disease were found to have marked reductions in both plasma lecithin-cholesterol acyltransferase activity (62%) and cholesterol ester concentration (46%) when compared with 11 normal subjects. The changes in cholesterol ester concentration were confined to high-density lipoprotein and very-low-density lipoprotein; the low-density lipoprotein fraction was not significantly altered. Examination of the plasma lecithin and lipoprotein cholesterol esters revealed that patients with liver disease had significantly greater amounts of saturated and monounsaturated fatty acids and less linoleic acid than normal subjects. Lipoprotein cholesterol ester kinetic studies were carried out in 2 normal subjects and 2 severely cirrhotic patients who simultaneously received [14C]mevalonic acid and high-density lipoprotein labeled with free [3H]cholesterol. A lipoprotein cholesterol ester model was developed that fit both the 3H and 14C data. The precursors of high-density lipoprotein cholesterol esters were free cholesterol and low-density lipoprotein cholesterol esters; the distribution pattern was in favor of low-density lipoprotein cholesterol esters in both groups of subjects (71% for normals and 88% for cirrhotics). The turnover of high-density lipoprotein cholesterol esters was similar in both groups of subjects, but the flux of free cholesterol into high-density lipoprotein cholesterol esters was greatly reduced in the cirrhotic patients. In cirrhotic patients, this represented only 9% and 12% of the total lipoprotein cholesterol ester synthesized; in the normal subjects, the values were 68% and 74%. The turnover of very-low-density lipoprotein cholesterol esters was greatly suppressed in the cirrhotic patients, and their precursor sources were high-density lipoprotein cholesterol esters and tissue free cholesterol. The low-density lipoprotein cholesterol ester precursors were very-low-density lipoprotein, low-density lipoprotein, and tissue free cholesterol. In the cirrhotic patients, much greater proportions (78% and 88%) of low-density lipoprotein cholesterol ester were derived from free cholesterol. Also, the turnover rates of these esters were reduced in the cirrhotic patients. The present report has provided evidence that cirrhotic patients derive most of their plasma lipoprotein cholesterol esters from an acyl-CoA-cholesterol acyltransferase free-cholesterol tissue source--most likely the intestine. By contrast, in normal subjects, the major contribution to plasma esters is via the introduction of newly formed cholesterol esters into the high-density lipoprotein fraction.