BACKGROUND: The liver is a key organ in the metabolism of cholesterol in humans. It is the only organ by which substantial amounts of cholesterol are excreted from the body, either directly as free cholesterol into the bile or after conversion to bile acids. The major part of cholesterol synthesis in the body occurs in the liver. Cholesterol is also taken up by the liver from plasma lipoproteins. The relative contributions of newly synthesised cholesterol and plasma lipoprotein cholesterol to bile acid synthesis and biliary cholesterol secretion, respectively, are not known in detail. AIMS: To determine how a rapid lowering of plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol influences the biliary secretion rates of cholesterol and bile acids in patients with cholesterol gallstones and complete biliary drainage. In this model with a completely interrupted enterohepatic circulation, the secretion of bile acids equals the new synthesis of bile acids in the liver. PATIENTS: Eight patients with common bile duct stones of cholesterol type undergoing conventional cholecystectomy and choledocholithotomy. METHODS: At operation a balloon occludable Foley catheter attached to a T tube was inserted into the bile duct with the balloon placed just past the distal limb of the T tube. The T tube was allowed to drain the bile externally. One week after the operation the Foley catheter balloon was inflated, creating complete biliary drainage. Twelve hours following the inflation plasma LDL apheresis was carried out for two hours. Bile was collected for 15 minute periods starting one hour before the apheresis and ending two hours after its termination. During the collection of bile, plasma lipids were analysed on several occasions. RESULTS: The plasma level of LDL cholesterol decreased by 26% from (mean (SEM)) 2.19 (0.29) to 1.63 (0.17) mmol/l during the LDL apheresis while high density lipoprotein (HDL) cholesterol in plasma was unaffected. During LDL apheresis apolipoprotein B containing lipoproteins bind to the column, causing a significant decrease of not only plasma LDL but also of VLDL cholesterol. The secretion rate of bile acids decreased significantly by 31% from 131 (38) to 90 (16) mumol/15 minutes (p = 0.045). The output of phospholipids also decreased by 19%. The biliary secretion rate of cholesterol was not, however, affected by the plasma LDL apheresis. CONCLUSIONS: The results suggest that, in patients with cholesterol gallstones and complete biliary drainage, lowering of plasma LDL and VLDL cholesterol reduces the biliary secretion rate--synthesis--of bile acids without affecting the biliary secretion rate of cholesterol.
BACKGROUND: The liver is a key organ in the metabolism of cholesterol in humans. It is the only organ by which substantial amounts of cholesterol are excreted from the body, either directly as free cholesterol into the bile or after conversion to bile acids. The major part of cholesterol synthesis in the body occurs in the liver. Cholesterol is also taken up by the liver from plasma lipoproteins. The relative contributions of newly synthesised cholesterol and plasma lipoprotein cholesterol to bile acid synthesis and biliary cholesterol secretion, respectively, are not known in detail. AIMS: To determine how a rapid lowering of plasma low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol influences the biliary secretion rates of cholesterol and bile acids in patients with cholesterol gallstones and complete biliary drainage. In this model with a completely interrupted enterohepatic circulation, the secretion of bile acids equals the new synthesis of bile acids in the liver. PATIENTS: Eight patients with common bile duct stones of cholesterol type undergoing conventional cholecystectomy and choledocholithotomy. METHODS: At operation a balloon occludable Foley catheter attached to a T tube was inserted into the bile duct with the balloon placed just past the distal limb of the T tube. The T tube was allowed to drain the bile externally. One week after the operation the Foley catheter balloon was inflated, creating complete biliary drainage. Twelve hours following the inflation plasma LDL apheresis was carried out for two hours. Bile was collected for 15 minute periods starting one hour before the apheresis and ending two hours after its termination. During the collection of bile, plasma lipids were analysed on several occasions. RESULTS: The plasma level of LDL cholesterol decreased by 26% from (mean (SEM)) 2.19 (0.29) to 1.63 (0.17) mmol/l during the LDL apheresis while high density lipoprotein (HDL) cholesterol in plasma was unaffected. During LDL apheresis apolipoprotein B containing lipoproteins bind to the column, causing a significant decrease of not only plasma LDL but also of VLDL cholesterol. The secretion rate of bile acids decreased significantly by 31% from 131 (38) to 90 (16) mumol/15 minutes (p = 0.045). The output of phospholipids also decreased by 19%. The biliary secretion rate of cholesterol was not, however, affected by the plasma LDL apheresis. CONCLUSIONS: The results suggest that, in patients with cholesterol gallstones and complete biliary drainage, lowering of plasma LDL and VLDL cholesterol reduces the biliary secretion rate--synthesis--of bile acids without affecting the biliary secretion rate of cholesterol.