Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Reduced cholesterol synthesis has been reported in patients with primary bi liary cirrhosis but no data are available on changes in cholesterol catabol ism induced by the disease. Serum levels of 7 alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholes terolemic or hypercholesterolemic) with primary biliary cirrhosis and in co ntrol subjects. To evaluate cholesterol synthesis, serum levels of lathoste rol were measured, and campesterol and sitosterol were considered to reflec t intestinal absorption and biliary elimination of sterols, In normocholest erolemic patients with primary biliary cirrhosis, lathosterol was significa ntly lower than in normocholesterolemic controls (P < 0.05) whereas no diff erence was found between hypercholesterolemic patients and hypercholesterol emic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primar y biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7 alpha-hydroxycholesterol was sightly higher than in controls. 27-Hydroxycholesterol was significantl y 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 patien ts 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 synthe sis and biliary elimination of sterols are impaired and also suggest that b oth the feedback regulation of retained bile acids on cholesterol 7 alpha-h ydroxylase and the scavenger effect on elevated serum cholesterol by choles terol 27-hydroxylase are deficient in these patients.