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Clofibrate therapy and gallstone induction

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Abstract

Two hundred consecutive patients, referred to a clinic established for the management of serum lipid disorders, were studied to assess the prevalence of gallbladder disease: 163 patients agreed to cholecystography of whom 23 had gallstones; 5 other patients had had cholecystectomy. There was a strong associction between clofibrate therapy and gallstones, which were found in 9 of 18 patients. Fifty-six patients with normal gallbladders had duodenal bile analyzed for lipid composition, and results were compared with those from 15 other patients with gallstones but normal serum lipids. Bile in hyperlipidemia and normolipidemic controls contained less cholesterol (9.21±3.48 mol/100 mol) than in clofibrate-treated patients (13.33±3.48 mol/100 mol, P<0.01), and in gallstone patients with normal serum lipids (11.87±4.52 mol/100 mol). There was no relationship demonstrable between patterns of hyperlipidemia or ischemic heart disease and the presence of gallbladder disease. There was also no association between biliary lipid composition and serum lipids or low-animal-fat diet. It is concluded that clofibrate therapy markedly increases biliary cholesterol content and is a potent lithogenic agent in patients not otherwise especially prone to gallstones. Since its role in prevention of ischemic heart disease is now uncertain, its continued wide use warrants close scrutiny.

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References

  1. Pertsemlidis D, Panveliwalla D, Ahrens EH: Effects of clotibrate and an oestrogen-progestin combination on fasting biliary lipids and cholic kinetics in man. Gastroenterology 66:565–573, 1974

    Google Scholar 

  2. Coronary Drug Project Research Group: Clofibrate and niacin in coronary heart disease. J Am Med Assoc 231:360–381, 1975

    Google Scholar 

  3. Kaye MD, Kern F: Clinical relationships of gallstones. Lancet 1:1228–1230, 1971

    Google Scholar 

  4. Bergman F, van der Linden W, Soperstrom J: The connection between myocardial infarction and gallstones in an autopsy series. Acta Pathol Microbiol Scand 73:559–564 1968

    Google Scholar 

  5. Bell GD, Lewis B, Petrie A, Dowling RH: Serum lipids in cholelithiasis—effect of chenoxeoxycholic acid therapy. Br Med J 3:520–523, 1973

    Google Scholar 

  6. Einarsson K, Hellstrom K, Kallner M: Gallbladder disease in hyperlipoproteinaemia. Lancet 1:484–487, 1975

    Google Scholar 

  7. Vlahcevic ZR, Bell CC, Juttijudata P, Swell L: Bile-rich duodenal fluid as an indicator of biliary lipid composition and its applicability to detection of lithogenic bile. Am J Dig Dis 16:797–802, 1971

    Google Scholar 

  8. Bateson MC, Ross PE, Murison J, Bouchier IAD: The effect of prolonged chenodeoxycholic acid feeding on bile in patients with and without gallstones. Gut 18:599–605, 1977

    Google Scholar 

  9. Murison J, Festi D, Ross PE, Bouchier IAD: The estimation of phospholipids in bile. Clin Chim Acta 68:159–166, 1975

    Google Scholar 

  10. Thistle JL, Schoenfield LJ: Lithogenic bile among young Indian women. N Engl J Med 284:177–181, 1971

    Google Scholar 

  11. Thomas PT, Hofmann AF: A simple calculation of the lithogenic index of bile: Expressing biliary lipid composition on rectangular co-ordinates. Gastroenterology 65:698–699, 1973

    Google Scholar 

  12. Bateson MC, Bouchier IAD: Prevalence of gallstones in Dundee: A necropsy survey. Br Med J 4:427–430, 1975

    Google Scholar 

  13. Friedman GD: The relationship between coronary heart disease and gallbladder disease: A critical review. Ann Intern Med 68:222–235, 1968

    Google Scholar 

  14. Valdivieso V, Palma R, Severin C, Antelana C, Contreras A: Effect of ageing on biliary lipid composition and bile acid metabolism in normal Chilean women. Gastroenterology 72:1144, 1977

    Google Scholar 

  15. Low-Beer TS, Wicks ACB, Heaton KW, Durrington P, Yeates J: Fluctuations in serum and bile lipid concentrations during the menstrual cycle. Br Med J 1:1568–1570, 1977

    Google Scholar 

  16. Bennion LJ, Ginsberg RL, Garnick MB, Bennett PH: Effects of the normal menstrual cycle on human gallbladder bile. N Engl J Med 294:1187, 1976

    Google Scholar 

  17. Oviedo MA, Ho K-J, Biss K, Soong S-J, Mickelson B, Taylor B: Gallbladder bile composition in different ethnic groups. Arch Pathol Lab Med 101:208–212, 1977

    Google Scholar 

  18. Metzger AL, Adler R, Heymsfield S, Grundy SM: Diurnal variation in biliary lipid composition. N Engl J Med 288:333–336, 1973

    Google Scholar 

  19. Williams CN, Morse JWI, Macdonald IA, Kotoor R, Riding MD: Increased lithogenicity of bile on fasting in normal subjects. Am J Dig Dis 22:189–194, 1977

    Google Scholar 

  20. Duane WC, Ginsberg RL, Bennion LJ: Effects of fasting on bile acid metabolism and biliary lipid composition in man. J Lipid Res 17:211–219, 1976

    Google Scholar 

  21. Sarles H, Crotte C, Gerolami A, Mule A, Domingo N, Hauton J: Influence of calorie intake and dietary protein on the biliary lipids. Scand J Gastroenterol 6:189–191, 1971

    Google Scholar 

  22. Sarles H, Hauton J, Planche NE, Lafont H, Gerolami A: Diet, cholesterol gallstones and composition of the bile. Am J Dig Dis 14:531–537, 1969

    Google Scholar 

  23. Bennion LJ, Grundy SM: Effects of obesity and calorie intake on biliary lipid metabolism in man. J Clin Invest 56:996–1011, 1975

    Google Scholar 

  24. Grundy SM: Effects of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridaemia. J Clin Invest 55:269–282, 1975

    Google Scholar 

  25. Den Besten L, Connor WE, Bell S: The effect of dietary cholesterol on the composition of human bile. Surgery 73:266–273, 1973

    Google Scholar 

  26. Pomare EW, Heaton KW, Low-Beer TS, Espiner HJ: The effect of wheat bran upon bile salt metabolism and upon the lipid composition of bile in gallstone patients. Am J Dig Dis 21:521–526, 1976

    Google Scholar 

  27. Freeman JB, Meyer PD, Printen KJ, Mason EE, Den Besten L: Analysis of bile in morbid obesity. Am J Surg 129:163–166, 1975

    Google Scholar 

  28. Mabee TH, Meyer P, Den Besten L, Mason EE: The mechanism of increased gallstone formation in obese human subjects. Surgery 79:460–468, 1976

    Google Scholar 

  29. Bennion LJ, Ginsberg RL, Garnick MB, Bennett PH: Effects of oral contraceptives on the gallbladder bile of normal women. N Engl J Med 294:189–192, 1976

    Google Scholar 

  30. Grundy SM, Ahrens EH, Salen G, Schreibman PH, Nestel PJ: Mechanism of action of clofibrate in cholesterol metabolism in patients with hyperlipidaemia. J Lipid Res 13:531–551, 1972

    Google Scholar 

  31. Van der Linden W, Nakayama F: Change of bile composition in man after administration of cholestyramine (a gallstone-dissolving agent in hamsters). Acta Chir Scand 135: 433–438, 1969

    Google Scholar 

  32. Mok HYI, Grundy SM: Effect of nicotinic acid on biliary lipids in man. Gastroenterology 73:A37/1235, 1977

    Google Scholar 

  33. Sturdevant RAL, Pearce ML, Dayton S: Increased prevalence of cholelithiasis in men ingesting a serum-cholesterollowering diet. N Engl J Med 288:24–27, 1973

    Google Scholar 

  34. Einarsson K, Hellstrom K, Kallner M: Bile acid kinetics in relation to sex, serum lipids, body weights and gallbladder disease in patients with various types of hyperlipoproteinaemia. J Clin Invest 54:1301–1311, 1974

    Google Scholar 

  35. Sodhi HS, Kudchodkar BJ: Synthesis of cholesterol in hypercholestorolaemia and its relationship to plasma triglycerides. Metabolism 22:895–912, 1973

    Google Scholar 

  36. Angelin B, Einarsson K, Hellstrom K, Kallner M: Elimination of cholesterol in hyperlipoproteinaemia. Clin Sci Mol Med 51:393–397, 1976

    Google Scholar 

  37. Miller NE, Nestel PJ: Triglyceride-lowering effect of chenodeoxycholic acid in patients with endogenous hypertriglyceridaemia. Lancet 2:929–931, 1974

    Google Scholar 

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Bateson, M.C., Maclean, D., Ross, P.E. et al. Clofibrate therapy and gallstone induction. Digest Dis Sci 23, 623–628 (1978). https://doi.org/10.1007/BF01072597

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