Serum and Hepatic Cholestanol, Squalene and Noncholesterol Sterols in Man: A Study on Liver Transplantation

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 5 alpha-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.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum sterols in patients with primary biliary cirrhosis and acute liver failure before and after liver transplantation

“…This relationship was also clear in end-stage PBC, but not as consistent as in ALF, as high serum cholestanol (ratios) indicated low ratios of only lathosterol/bilirubin and campesterol/sitosterol. Accordingly, our results are in accordance with earlier studies among PBC-patients, which showed that hypercholestanolemia and accumulation of cholestanol in tissues develop gradually during worsening state of PBC [10,11,15,16].…”

“…These liver diseases were chosen, because they both represent a cholestatic liver failure, and because serum sterol profiles and cholesterol metabolism of ALF of unknown etiology have not been elucidated so far. In this respect, PBC-patients have been studied most widely [10,11,15,16], and PBC is one of the commonest indications for LTX in Finland; thus, they form a suitable reference group and study population of sufficient size. The following hypotheses were tested: (I) patients with ALF and PBC have differential patterns in their serum sterols and sterol metabolism before and after LTX [10,15], (II) certain profiles of serum sterols are related to poor liver function prior to LTX [15,16], and (III) ALF can be caused by abnormal sterol metabolism [17].…”

Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

“…Changes in cholesterol metabolism are not mirrored by routine serum cholesterol and lipoprotein measurements [28] . Moreover, the direct methods available to evaluate cholesterol metabolism are complex and laborious, and require labeling techniques, feces collection, and dietary recalls over several days.…”

“…On the other hand, diet-derived plant sterols (e.g., campesterol and sitosterol) and the liversynthesized cholesterol metabolite cholestanol are markers of cholesterol absorption efficiency [30] . These markers have been investigated in PBC before and after LT [15,28,[32][33][34] . Compared to that in healthy controls, intestinal cholesterol absorption is reportedly reduced by 2/3 in cases of prolonged severe intrahepatic cholestasis leading to cirrhosis and end-stage liver failure, as seen in PBC [35] .…”

“…Cholestasis impairs the intestinal absorption of all types of sterols due to poor micellar formation secondary to reduced bile formation and excretion. However, striking increases of serum and hepatic plant sterol and cholestanol levels are also observed, indicating that the serum levels of plant sterols and cholestanol do not correctly mirror cholesterol absorption in cholestasis [15,28] . These changes can be used as biomarkers of the degree of cholestasis, with serum cholestanol/cholesterol being an even more sensitive marker of cholestasis among earlystage PBC patients than serum bilirubin [33] .…”