BILIARY LIPID-SYNTHESIS AND SECRETION IN GALLSTONE PATIENTS BEFORE AND DURING TREATMENT WITH CHENODEOXYCHOLIC ACID

  • 1 January 1980
    • journal article
    • research article
    • Vol. 95  (6) , 816-826
Abstract
The interrelationships between biliary lipid secretion and the hepatic activities of the rate-limiting enzymes for bile acid and cholesterol synthesis were not investigated in patients with gallstones before and during desaturation therapy. Liver biopsies for enzyme assays and biliary lipid secretion measurements were performed in 12 patients with gallstones before chenodeoxycholic acid therapy and in 9 of these patients at 9 mo. of therapy. Six nongallstone control patients underwent only the lipid secretion measurements. In the patients with gallstones before treatment, all of whom had saturated bile, increased cholesterol secretion correlated directly with increased HMGCoAR [hydroxymethylglutaryl coenzyme A reductase] activity, whereas bile acid and phospholipid secretion rates were significantly lower than in controls. During desaturation in response to chenodeoxycholic acid, biliary cholesterol and phospholipid secretion rates decreased significantly and bile acid secretion was unchanged. Both HMGCoAR and cholesterol 7.alpha.-hydroxylase activities decreased significantly, but the correlation between HMGCoAR and cholesterol secretion was lost. No correlation was found between cholesterol 7.alpha.-hydroxylase activity and bile acid secretion during therapy. Enzyme assays were performed on single liver samples obtained at the same time of day but 48 h before the lipid secretion measurements. The mechanism of biliary cholesterol saturation in patients with gallstones probably is related primarily to increased hepatic cholesterol synthesis, whereas desaturation during chenodeoxycholic acid therapy involves altered relationships among hepatic enzyme activities and biliary lipid secretions.