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Abstract

Serum noncholesterol sterols indicate overall cholesterol metabolism in a variety of experimental and clinical conditions. In patients with advanced primary biliary cirrhosis serum cholestanol, a 5ä-derivative of cholesterol, is markedly increased, and cholesterol precursors, which are indicators of cholesterol synthesis, are clearly reduced, as is the ratio of plant sterols (campesterol/sitosterol). Therefore these variables were studied in the livers and sera of 23 patients undergoing liver transplantation (16 patients with chronic liver disease, 4 with acute liver failure and 3 receiving second liver) and in 10 healthy controls. A most striking finding was the markedly high liver and serum levels of cholestanol in patients with chronic end-stage liver disease, a finding specific for cholestanol but not for other sterols. Of the cholesterol precursor sterols, lathosterol exhibited low contents in both the serum and liver of the cirrhotic patient group, supposedly reflecting decreased cholesterol synthesis. In contrast to the largely similar levels of noncholesterol sterols in serum and liver and the positive correlations between the two sources, the serum squalene levels were markedly lower than the hepatic levels, with a negative correlation between the serum and the liver, suggesting that serum squalene content poorly reflects cholesterol synthesis. In contrast to campesterol, serum and liver sitosterol tended to show increases, and the serum and hepatic campesterol/sitosterol ratios were lower in the chronic liver disease patients than in the controls, probably because of the more consistently impaired biliary elimination of sitosterol in those patients. The findings show that cholestanol is markedly increased and that lathosterol and the campesterol/sitosterol ratio are decreased in both the serum and the liver of patients with chronic end-stage liver disease. Unlike squalene, serum noncholesterol sterols are quite evenly distributed with the respective hepatic sterols. Gas-liquid chromatographic quantitation of these sterols from nonsaponifiable serum lipids may offer a new means of determining the actual end stages of chronic liver diseases. (HEPATOLOGY 1992;15:863–870).