phytosterols and Liver-Cirrhosis--Biliary

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7alpha-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients. acids via the acidic pathway.

Topics: Aged; Bile Acids and Salts; Cholesterol; Female; Humans; Hydroxycholesterols; Intestinal Absorption; Liver Cirrhosis, Biliary; Male; Middle Aged; Phytosterols; Sitosterols

A randomized placebo-controlled 2-year study was performed in 69 patients with primary biliary cirrhosis (PBC) on serum lipids during ursodeoxycholic acid (URSO) and colchicine treatments. In addition to serum bilirubin and alkaline phosphatase (AFOS), two variables considered to reflect liver function, serum lipoproteins, cholesterol precursors (squalene, delta 8-cholestenol, lathosterol and desmosterol), markers of cholesterol synthesis, cholestanol and plant sterols (campesterol and sitosterol), markers of liver function and cholesterol absorption, were studied before and during the treatments. Serum bilirubin was inconsistently improved by URSO, whereas improvement of AFOS values was better by URSO than colchicine, especially in patients with initially more advanced PBC. Serum total cholesterol was reduced by both drugs, very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) cholesterol by URSO. Cholesterol precursor sterols were increased by both URSO and colchicine mainly in patients with initially less severe PBC. On the other hand, the cholestanol values were markedly increased initially, and the values were related to bilirubin during the 2-year period, were further increased in the placebo group, and reduced in the URSO and colchicine groups, so that the improvement was highest in the URSO-treated patients with the severe form of PBC. The increase of the serum plant sterols, particularly that of sitosterol, was retarded by the two drugs so that the campesterol/sitosterol ratio, which was related to serum bilirubin, was increased especially in the cases with initially more advanced PBC.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Alkaline Phosphatase; Bilirubin; Cholestanol; Cholesterol; Colchicine; Humans; Liver Cirrhosis, Biliary; Middle Aged; Phytosterols; Placebos; Ursodeoxycholic Acid

Liver diseases modify sterol metabolism. Liver transplantation (LTX) provides a model to evaluate the impact of disease-affected liver on sterol metabolism.. We studied serum sterol profiles and their relationships to other biochemical markers in consecutive cholestatic patients with acute liver failure (ALF, n=39) and end-stage primary biliary cirrhosis (PBC, n=67) before and 27d after LTX. Accordingly, we determined serum levels of sterols, bilirubin and prealbumin.. Due to weak cholesterol synthesis of ALF-patients before LTX, their serum levels of cholesterol, lathosterol/cholesterol, cholestanol/cholesterol and lathosterol/campesterol were 18%-41% lower (P<0.05 for each) than in PBC, but ratios of phytosterols to cholesterol were equal. In general, non-cholesterol sterol ratios reflected bilirubin and prealbumin concentrations. Interrelation of surrogate sterols showed that homeostasis of cholesterol metabolism prevailed in lowest cholestanol tertile of ALF-patients consistently, but not in PBC. After LTX, cholesterol levels and lathosterol ratios increased in both groups and phytosterol ratios decreased (P<0.01). Cholestanol decreased profoundly in PBC, but remained 26% higher than in ALF (P<0.05).. Homeostasis of cholesterol metabolism was maintained only in ALF. Metabolism of phytosterols was equal in study groups. PBC- and ALF-patients have differential patterns in their serum sterols and cholesterol metabolism.

Topics: Adult; Bilirubin; Biomarkers; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Failure, Acute; Liver Transplantation; Male; Middle Aged; Phytosterols; Prealbumin; Sterols

Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end-stage of primary biliary cirrhosis (PBC) - prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6-3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.

Topics: Adult; Aged; Bilirubin; Biomarkers; Cholestanol; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Function Tests; Liver Transplantation; Male; Middle Aged; Phytosterols; Sitosterols; Sterols

The concentration of serum cholestanol, a 5 alpha-saturated derivative of cholesterol, is increased in primary biliary cirrhosis proportionally to impaired liver function for unknown reasons. The purpose of this study was to analyze serum cholestanol level and its biliary and fecal elimination, and relate the results to cholesterol absorption and metabolism.. Sixteen patients with primary biliary cirrhosis and 44 non-primary biliary cirrhosis controls were studied. Squalene and non-cholesterol sterols were analyzed by gas-liquid chromatography, cholesterol absorption by the peroral double-isotope continuous feeding method, and neutral and acidic sterols in bile and feces by gas-liquid chromatography.. In primary biliary cirrhosis, the mean level of serum cholesterol was normal, but the cholestanol/cholesterol proportion was increased 4-fold, and the proportion was related to the serum bile acid and bilirubin levels. The mean biliary cholestanol proportion and the biliary secretion rate were increased 5- and 2-fold, respectively, suggesting that at low cholestanol absorption cholestanol synthesis was increased. Calculated clearance of serum cholestanol into bile was decreased. The fecal output was within the control limits, so that intestinal cholestanol production was lowered in primary biliary cirrhosis. In addition, serum and biliary plant sterol proportions were increased in primary biliary cirrhosis, but their biliary secretion was unchanged, while those of cholesterol, bile acids, phospholipids, and cholesterol precursor sterols were markedly reduced.. We conclude that an enhanced cholestanol synthesis and a cholestasis-induced decrease in biliary clearance of serum cholestanol contribute to the excessively high serum cholestanol level in primary biliary cirrhosis. In addition, reduced bile acid synthesis may contribute to the increased serum cholestanol content.

Topics: Absorption; Bile; Bile Acids and Salts; Bilirubin; Cholestanol; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Phytosterols

Proportions of cholesterol precursors (squalene, delta 8-cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol) and cholestanol to cholesterol in serum were measured before and serially after liver transplantation in eight patients with primary biliary cirrhosis (PBC) and three with acute liver necrosis. The preoperative proportions of cholestanol were 12 and 3-times higher in the PBC and necrosis groups, respectively, than in a control group of 27 individuals, while those of lathosterol were low in both groups and the campesterol/sitosterol ratio in the PBC group. During the operation the proportions of cholestanol fell sharply and those of lathosterol rose especially in the PBC group. During the postoperative follow-up of 5 weeks the proportions of the non-cholesterol sterols were markedly improved especially in the necrosis group yet those of cholestanol remained high and the campesterol/sitosterol ratios low, particularly in the PBC group. The proportions of lathosterol increased gradually almost to the control limits within the postoperative 5-week period, whereas those of desmosterol decreased. The non-cholesterol sterol values were not related to acute rejections, while significant correlations of cholestanol to liver function tests was found especially at the end of the follow-up.

Topics: Acute Disease; Adult; Cholestanol; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Liver Transplantation; Male; Middle Aged; Necrosis; Phytosterols; Protein Precursors; Sitosterols; Squalene

Topics: Bilirubin; Biomarkers; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Diseases; Liver Transplantation; Male; Phytosterols; Reference Values; Sitosterols

Serum levels of cholesterol precursors (squalene, delta 8-cholestanol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol), cholestanol and cholestanol/noncholesterol sterol ratios were related to liver damage and liver transplantation indications in healthy controls (n = 26) and in 31 patients with primary biliary cirrhosis divided into group I (S-bilirubin less than 21 mumol/L; n = 14), group II (S-bilirubin 21 to 108 mumol/L; n = 7) and group III (elected for liver transplantation; S-bilirubin 109 to 520 mumol/L; n = 10). The mean serum respective lathosterol levels in controls and in group I were three and two times higher than those in groups II and III, respectively. The plant sterol contents were higher in group II than in groups I and III and the campesterol/sitosterol ratios were lowest in group III. The serum cholestanol levels were high even in group I (i.e., in patients without icterus) and increased progressively to group III, up to 6 and 13 times those in group I and the control group, respectively. The cholestanol/noncholesterol sterol ratios increased progressively from the controls to groups I, II and III. The serum cholestanol levels were positively related to serum bilirubin levels in all primary biliary cirrhosis patients (n = 31, r = 0.906) and to the plant sterol levels in the control group and group I, but significantly negatively in group III. The cholestanol vs. precursor sterol correlations were negative in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cholestanol; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Function Tests; Liver Transplantation; Male; Phytosterols; Sitosterols; Sterols

We measured serum cholesterol precursors (squalene, delta 8-cholestenol, desmosterol, lathosterol, cholestanol) and plant sterols (campesterol, sitosterol, and avenasterol) from 11 patients (one man) with primary biliary cirrhosis (PBC) and 13 healthy women matched for age and weight. In PBC serum total cholesterol was increased (9.4 versus 5.9 mmol/l; p less than 0.05), whereas serum cholestanol in terms of mmol/mol of cholesterol was elevated fourfold. In similar terms, serum plant sterols, especially sitosterol and avenasterol, were modestly increased, whereas most of serum cholesterol precursors were decreased. The serum contents of cholestanol were negatively associated with those of serum cholesterol precursors and positively with those of sitosterol and avenasterol with the serum cholesterol concentration. The liver function tests were positively related to serum cholestanol contents (r value ranged from 0.588 to 0.839 for alkaline phosphatase, aspartate aminotransferase, alanine amino-transferase, and bilirubin). The findings suggest that in cholestatic liver disease reduced serum cholesterol precursor contents reflect reduced cholesterol synthesis, whereas increased serum plant sterol and cholestanol contents are determined mainly by impaired biliary elimination.

Topics: Adult; Cholestanols; Cholesterol; Female; Humans; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Phytosterols