Gallstone dissolution with chenodeoxycholic acid
- 21 Downloads
- 5 Citations
Summary
Out of 95 patients with radiolucent gallstones who enrolled in a clinical study with chenodeoxycholic acid (CDC) for gallstone dissolution 75 patients with cholecystolithiasis completed 12 months of treatment. As a side effect 31% of patients reported intermittent diarrhea which did not cause cessation of therapy or missing of work. The incidence of biliary colic was markedly decreased during treatment in comparison to the rate in the year before. From more than 20 laboratory values checked before start and every 3 months during therapy only aminotransferases increased up to 3 fold in 20% of patients. γ-GT elevated in 31% of patients before treatment improved in half of these patients during therapy. Gallstone dissolution defined as 30% or more diminution of the gallstone area on comparable x-rays occurred in 40% of patients. Analysis of factors showed that gallstones above 2 cm in diameter did not dissolve. When the dose of CDC was retrospectively related to body weight a success rate of 68% was found in the group taking more than 13 mg CDC/kg/day. The lithogenic index determined at 6 and 12 months had significantly decreased after 6 months in patients with success. This study demonstrates that medical dissolution of gallstones with chenodeoxycholic acid should be performed in patients with radiolucent stones of less than 2 cm in diameter and with a dose above 13 mg CDC/kg body weight/day. Under these conditions the success rate is above 60% accompanied by minimal side effects.
Key words
Gallstone dissolution Chenodeoxycholic acid ManGallensteinauflösung mit Chenodesoxycholsäure
Zusammenfassung
Von 95 Patienten mit röntgenologisch nichtschattengebenden Gallensteinen, die an einer klinischen Studie zur medikamentösen Steinauflösung mit Chenodesoxycholsäure (CDC) teilnahmen, wurden 75 Patienten mit Cholecystolithiasis über 12 Monate behandelt. Als Nebenwirkung bemerkten 31% der Patienten intermittierend Durchfall, der jedoch nicht zum Absetzen der Behandlung oder Arbeitsausfall führte. Die Häufigkeit der Gallenkoliken war während der Behandlung deutlich herabgesetzt im Vergleich zum vorangehenden Jahr. Von über 20 Laborwerten, die vor Beginn und alle 3 Monate während der Therapie überprüft wurden, stiegen nur die Aminotransferasen bei 20% der Patienten bis zum dreifachen der Norm. γ-GT war vor der Behandlung bei 31% der Patienten erhöht und verbesserte sich bei der Hälfte dieser Patienten während der Therapie. Eine Auflösung der Gallensteine, definiert als Verkleinerung der Gallensteinfläche auf vergleichbaren Röntgenbildern um 30% oder mehr, wurde bei 40% der Patienten beobachtet. Die Analyse der Faktoren zeigte, daß Gallensteine über 2 cm Durchmesser sich nicht auflösten. Wenn die CDC-Dosis retrospektiv auf das Körpergewicht bezogen wurde, fand sich die höchste Erfolgsrate mit 68% in jener Patientengruppe, die über 13 mg CDC/kg/Tag einnahm. Der lithogene Index, der nach 6 und 12 Monaten Behandlung bestimmt wurde, war nach 6 Monaten signifikant vermindert bei Patienten mit Gallensteinauflösung.
Diese Studie zeigt, daß die medikamentöse Auflösung von Gallensteinen mit Chenodesoxycholsäure bei Patienten mit nichtschattengebenden Gallensteinen von weniger als 2 cm Durchmesser durchgeführt werden sollte mit einer Dosierung von mehr als 13 mg CDC/kg Körpergewicht/Tag. Unter diesen Bedingungen liegt die Erfolgsrate über 60% bei gleichzeitig minimalen Nebenwirkungen.
Schlüsselwörter
Gallensteinauflösung Chenodesoxycholsäure MenschPreview
Unable to display preview. Download preview PDF.
References
- 1.Admirand, W.H., Small, D.M.: The physicochemical basis of cholesterol gallstone formation in man. J. Clin. Invest.47, 1043–1048 (1968)PubMedGoogle Scholar
- 2.Bateson, M.C., Murison, J., Ross, P.E., Bouchier, J.A.D.: Comparison of fixed doses of chenodeoxycholic acid for gallstone dissolution. Lancet1, 1111–2214 (1978)PubMedGoogle Scholar
- 3.Bell, D.G., Dowling, R.H., Whitney, B., Sutor, D.J.: The value of radiology in predicting gallstone type when selecting patients for medical treatment. Gut16, 359–364 (1975)PubMedGoogle Scholar
- 4.Bell, G.D., Mok, H.Y., Thwe, M., Murphy, G.M., Henry, K., Dowling, R.H.: Liver structure and function in cholelithiasis: effect of chenodeoxycholic acid. Gut15, 165–172 (1974)PubMedGoogle Scholar
- 5.Carey, M.C., Small, D.M.: The physical chemistry of Cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. J. Clin. Invest.61, 998–1026 (1978)PubMedGoogle Scholar
- 6.Coyne, M.J., Bonorris, G.G., Goldstein, L.J., Schoenfield, L.J.: Effect of chenodeoxycholic acid and phenobarbital on the rate-limiting enzymes of hepatic cholesterol and bile acid synthesis in patients with gallstones. J. Lab. Clin. Med.87, 281–291 (1976)PubMedGoogle Scholar
- 7.Danzinger, R.G., Hofmann, A.F., Schoenfield, L.J., Thistle, J.L.: Dissolution of cholesterol gallstones by chenodeoxycholic acid. New Engl. J. Med.286, 1–8 (1972)PubMedGoogle Scholar
- 8.Danzinger, R.G., Hofmann, A.F., Thistle, J.L., Schoenfield, L.J.: Effect of oral chenodeoxycholic acid on bile acid kinetics and biliary lipid composition in women with cholelithiasis. J. Clin. Invest.52, 2809–2821 (1973)PubMedGoogle Scholar
- 9.Debongnie, J.C., Philips, S.F.: Capacity of the human colon to absorb fluid. Gastroenterology74, 698–703 (1978)PubMedGoogle Scholar
- 10.Den Besten, L., Connor, W.E., Bell, S.: The effect of dietary cholesterol on the composition of human bile. Surgery73, 266–273 (1973)PubMedGoogle Scholar
- 11.Edholm, P.: Gallbladder evacuation in the normal male induced by cholecystokinin. Acta Radiol.53, 257–265 (1960)PubMedGoogle Scholar
- 12.Friedman, G.D., Kannel, W.B., Dawler, T.R.: The epidemiology of gallbladder disease: observations in the Framingham study. J. Chron. Dis.19, 273–292 (1966)PubMedGoogle Scholar
- 13.Fromm, H., Eschler, A., Töllner, D., Canzler, H., Schmidt, F.W.: Untersuchungen zur Gallensteinauflösung in vivo. Dtsch. Med. Wochenschr.100, 1619–1624 (1975)PubMedGoogle Scholar
- 14.Hack, J.: Beziehungen zwischen Gallensteinen und Gallenblasenveränderungen. Dissertation Johannes Gutenberg-Universität Mainz 1978Google Scholar
- 15.Hegardt, F.G., Dam, H.: The solubility of cholesterol in aqueous solution of bile salts and bile salts plus lecithin. Z. Ernährungswiss.10, 223–233 (1971)Google Scholar
- 16.Hofmann, A.F.: Die Gallensäuren in der Klinischen Medizin: Was ist neu und was hat praktische Bedeutung? Internist18, 195–200 (1977)PubMedGoogle Scholar
- 17.Ingelfinger, F.J.: Digestive disease as a national problem: V. Gallstones. Gastroenterology55, 102–104 (1968)PubMedGoogle Scholar
- 18.Iser, J.J., Dowling, R.H., Mok, H.Y., Bell, G.D.: Chenodeoxycholic acid treatment of gallstones: A follow-up report and analysis of factors influencing response to therapy. New Engl. J. Med.293, 378–383 (1975)PubMedGoogle Scholar
- 19.Leuschner, U., Reber, E., Erb, W.: Erfahrungen bei der Behandlung von Gallensteinpatienten mit Chenodesoxycholsäure. Dtsch. Med. Wochenschr.102, 156–160 (1977)PubMedGoogle Scholar
- 20.Lindström, O.G.: Frequency of gallstone disease in a well-defined Swedish population. A prospective necropsy study in Malmö. Scand. J. Gastroenterol.12, 341–346 (1977)PubMedGoogle Scholar
- 21.Makino, J., Shinozaki, K., Yoshino, K.: Dissolution of cholesterol gallstones by ursodeoxycholic acid. Jpn. J. Gastroenterol.72, 690–691 (1975)Google Scholar
- 22.Maugdal, D.P., Bird, R., Blackwood, W.S., Northfield, T.C.: Low-cholesterol diet: enhancement of effect of CDCA in patients with gallstones. Br. Med. J.2, 851–853 (1978)PubMedGoogle Scholar
- 23.Metzger, A.L., Heymsfield, S., Grundy, S.: The lithogenic index — a numerical expression for the relative lithogenicity of bile. Gastroenterology62, 499–500 (1972)PubMedGoogle Scholar
- 24.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. Lancet2, 253–257 (1974)PubMedGoogle Scholar
- 25.Northfield, T.C., Hofmann, A.F.: Biliary lipid output during three meals and an overnight fast. Gut16, 1–17 (1975)PubMedGoogle Scholar
- 26.Redinger, R.N., Small, D.M.: Bile composition, bile salt metabolism and gallstones. Arch. Int. Med.130, 618–638 (1972)Google Scholar
- 27.Sachs, L.: Angewandte Statistik, 4th ed. Berlin, Heidelberg, New York: Springer 1974Google Scholar
- 28.Schäfer, J.: Faktoren der Gallensteinauflösung in vitro. Dissertation Johannes Gutenberg-Universität Mainz 1977Google Scholar
- 29.Schwarz, H.P., v. Bergman, K., Paumgartner, G.: A simple method for the estimation of bile acids in serum. Clin. Chim. Acta50, 197–206 (1974)Google Scholar
- 30.Silva, G.S.P.: A simple method for computing the volume of the human gallbladder. Radiology52, 94–101 (1949)Google Scholar
- 31.Sperry, W.M., Webb, M.: A revision of the Schoenheimer-Sperry method for cholesterol determination. J. Biol. Chem.187, 97–102 (1950)PubMedGoogle Scholar
- 32.Stiehl, A., Raedsch, R., Regula, M., Kommerell, B.: Zur Behandlung von Patienten mit Cholesteringallensteinen mit Chenodesoxycholsäure: Veränderungen im Gallensäurestoffwechsel. Inn. Med.2, 13–18 (1975)Google Scholar
- 33.Stiehl, A., Czygan, P., Kommerell, B., Weis, H.J., Holtermüller, K.H.: Ursodeoxycholic acid versus chenodeoxycholic acid. Comparison of their effects on bile acid and bile lipid composition in patients with cholesterol gallstones. Gastroenterology75, 1016–1020 (1978)PubMedGoogle Scholar
- 34.Stiehl, A., Czygan, P., Raedsch, R.: Sulphation of lithocholate in patients during chenodeoxycholate treatment a protective mechanism. In: Advances in Bile Acid Research, Matern, S., Hackenschmidt, J., Back, P. (eds.), p. 347–350. Stuttgart, New York: Schattauer 1975Google Scholar
- 35.Tao, J.C., Cussler, E.L., Evans, D.F.: Accelerating gallstone dissolution. Proc. Nat. Acad. Sci.71, 3917–3921 (1974)PubMedGoogle Scholar
- 36.Thistle, J.L., Hofmann, H.F.: Efficacy and specificity of chenodeoxycholic acid therapy for dissolving gallstones. New Engl. J. Med.285, 655–659 (1973)Google Scholar
- 37.Thomas, P.J., Hofmann, A.F.: A simple calculation of the lithogenic index of bile: expressing biliary lipid composition on rectangular coordinates. Gastroenterology65, 698–700 (1973)PubMedGoogle Scholar
- 38.Vlahcevic, Z.R., Bell, C.C., Buhac, J., Farrar, J.T., Swell, L.: Diminished bile acid pool size in patients with gallstones. Gastroenterology59, 165–173 (1970)PubMedGoogle Scholar
- 39.Vlahavic, Z.R., Bell, C.C. Jr., Juttijudata, P., Swell, L.: Bilerich duodenal fluid as an indicator of biliary lipid composition and its applicability to detection of lithogenic bile. Dig. Dis.16, 797–802 (1971)Google Scholar
- 40.Wassner, U.J.: Das Gallensteinleiden im Spiegel der Statistik. Langenbecks Arch. u. Dtsch. Z. Chir.285, 160–182 (1957)Google Scholar
- 41.Williams, G., Tenida, N., Maton, P.N., Murphy, G.M., Dowling, R.H.: The biliary cholesterol saturation index (SI) in ursodeoxycholic acid-rich bile: is the Carey correction necessary when predicting gallstone dissolution! 5th International Symposium on Bile Acids, Cortina d'Ampezzo 1979, p. 56Google Scholar
- 42.Zilversmit, D.B., Davis, A.K.: Microdetermination of plasma phospholipids by trichloroacetic acid and precipitation. J. Lab. Clin. Med.35, 155–158 (1950)PubMedGoogle Scholar