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. 1978 Jun 10;1(6126):1509–1512. doi: 10.1136/bmj.1.6126.1509

Resistance to chenodeoxycholic acid (CDCA) treatment in obese patients with gall stones*

J H Iser, Paul N Maton, Gerard M Murphy, R Hermon Dowling
PMCID: PMC1605021  PMID: 656777

Abstract

In most patients with radiolucent gall stones who were given chenodeoxycholic acid (CDCA) in doses of 13-15 mg/kg body weight/day the bile became unsaturated in cholesterol, and their gall stones dissolved. The patients whose stones did not dissolve were significantly heavier and fatter than the responders, which suggested that obese patients might be “resistant” to the effects of CDCA. To test this hypothesis, 32 consecutive patients presenting for medical treatment of gall stones had their ideal body weight (IBW) and estimated body fat mass calculated. The eight most obese and the eight least obese patients were then selected, and their fasting bile lipid responses to CDCA 13-15 mg/kg/day were measured. The very obese patients were also given larger doses, and any changes in bile lipid composition were studied in relation to subsequent gall-stone dissolution.

Before treatment the obese patients had a higher mean biliary cholesterol saturation index than the non-obese patients, and this difference was maintained during treatment with the normal dose of CDCA: the bile in the obese patients remained supersaturated while that in the non-obese became unsaturated with cholesterol. When the obese patients were given larger doses of CDCA their bile ultimately became unsaturated in cholesterol. Gall stones dissolved partially or completely in five of the eight non-obese patients after 6-18 months of 13-15 mg CDCA/kg/day, but none of the obese patients showed any response after comparable periods of treatment with this standard dose. With increased doses and unsaturated bile, however, three of the obese patients showed partial gall-stone dissolution after 3-12 months' treatment and one showed complete gall-stone dissolution after three years' treatment.

These results suggest that when giving CDCA to patients with gall stones, larger than normal doses (some 18-20 mg/kg/day) should be prescribed. Alternatively the lipid composition of the patients' bile should be monitored by duodenal intubation and the CDCA dose increased until the bile becomes unsaturated in cholesterol.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adler R. D., Bennion L. J., Duane W. C., Grundy S. M. Effects of low dose chenodeoxycholic acid feeding on biliary lipid metabolism. Gastroenterology. 1975 Feb;68(2):326–334. [PubMed] [Google Scholar]
  2. Bell G. D., Dowling R. H., Whitney B., Sutor D. J. The value of radiology in predicting gallstone type when selecting patients for medical treatment. Gut. 1975 May;16(5):359–364. doi: 10.1136/gut.16.5.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennion L. J., Ginsberg R. L., Gernick M. B., Bennett P. H. Effects of oral contraceptives on the gallbladder bile of normal women. N Engl J Med. 1976 Jan 22;294(4):189–192. doi: 10.1056/NEJM197601222940403. [DOI] [PubMed] [Google Scholar]
  4. Bennion L. J., Grundy S. M. Effects of obesity and caloric intake on biliary lipid metabolism in man. J Clin Invest. 1975 Oct;56(4):996–1011. doi: 10.1172/JCI108180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. EDWARDS K. D., WHYTE H. M. The simple measurement of obesity. Clin Sci. 1962 Jun;22:347–352. [PubMed] [Google Scholar]
  6. Einarsson K., Hellström K., Kallner M. Gallbladder disease in hyperlipoproteinaemia. Lancet. 1975 Mar 1;1(7905):484–487. doi: 10.1016/s0140-6736(75)92831-7. [DOI] [PubMed] [Google Scholar]
  7. Hegardt F. G., Dam H. The solubility of cholesterol in aqueous solutions of bile salts and lecithin. Z Ernahrungswiss. 1971 Apr;10(3):223–233. doi: 10.1007/BF02020933. [DOI] [PubMed] [Google Scholar]
  8. Iser J. H., Dowling H., Mok H. Y., Bell G. D. Chenodeoxycholic acid treatment of gallstones. A follow-up report and analysis of factors influencing response to therapy. N Engl J Med. 1975 Aug 21;293(8):378–383. doi: 10.1056/NEJM197508212930804. [DOI] [PubMed] [Google Scholar]
  9. Iser J. H., Murphy G. M., Dowling R. H. Speed of change in biliary lipids and bile acids with chenodeoxycholic acid--is intermittent therapy feasible? Gut. 1977 Jan;18(1):7–15. doi: 10.1136/gut.18.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Metzger A. L., Heymsfield S., Grundy S. M. The lithogenic index--a numerical expression for the relative lithogenicity of bile. Gastroenterology. 1972 Mar;62(3):499–501. [PubMed] [Google Scholar]
  11. Mok H. Y., Bell G. D., Dowling R. H. Effect of different doses of chenodeoxycholic acid on bile-lipid composition and on frequency of side-effects in patients with gallstones. Lancet. 1974 Aug 3;2(7875):253–257. doi: 10.1016/s0140-6736(74)91415-9. [DOI] [PubMed] [Google Scholar]
  12. Mok H. Y., Perry P. M., Dowling R. H. The control of bile acid pool size: effect of jejunal resection and phenobarbitone on bile acid metabolism in the rat. Gut. 1974 Apr;15(4):247–253. [PMC free article] [PubMed] [Google Scholar]
  13. Nicolau G., Shefer S., Salen G., Mosbach E. H. Determination of hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity in man. J Lipid Res. 1974 Jan;15(1):94–98. [PubMed] [Google Scholar]
  14. Northfield T. C., LaRusso N. F., Hofmann A. F., Thistle J. L. Biliary lipid output during three meals and an overnight fast. II. Effect of chenodeoxycholic acid treatment in gallstone subjects. Gut. 1975 Jan;16(1):12–17. doi: 10.1136/gut.16.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ponz De Leon M., Ferenderes R., Carulli N. Composizione della bile in popolazioni ad elevato rischio di colelitiasi. Minerva Med. 1976 Nov 3;67(53):3483–3490. [PubMed] [Google Scholar]
  16. Shaffer E. A., Small D. M. Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity. J Clin Invest. 1977 May;59(5):828–840. doi: 10.1172/JCI108705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Swell L., Bell C. C., Jr, Gregory D. H., Vlahcevic Z. R. The cholesterol saturation index of human bile. Am J Dig Dis. 1974 Mar;19(3):261–265. doi: 10.1007/BF01072543. [DOI] [PubMed] [Google Scholar]
  18. Trotman B. W., Petrella E. J., Soloway R. D., Sanchez H. M., Morris T. A., 3rd, Miller W. T. Evaluation of radiographic lucency or opaqueness of gallstones as a means of identifying cholesterol or pigment stones. Correlation of lucency or opaqueness with calcium and mineral. Gastroenterology. 1975 Jun;68(6):1563–1566. [PubMed] [Google Scholar]

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