Gallstones – Nonsurgical treatment

Nonsurgical treatment of gallstones
Salam F Zakko, MD, FACP, AGAF
Section Editor:
Sanjiv Chopra, MD, MACP
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF


Over the past several decades, four modalities for the nonsurgical treatment of gallbladder stones were evaluated and gained some popularity at various times. These included: 

?Oral medical dissolution with bile acids

?Percutaneous cholecystostomy with stone extraction

?Percutaneous or transnasal topical solvent dissolution

?Extracorporeal shock wave lithotripsy

To continue reading this article, you must log in with your personal, hospital, or group practice subscription.
Literature review current through: Mar 2018. | This topic last updated: Jan 15, 2018.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of UpToDate content is governed by the UpToDate Terms of Use. ©2018 UpToDate, Inc. All rights reserved.


  1. Darzi A, Geraghty JG, Williams NN, et al. The pros and cons of laparoscopic cholecystectomy and extracorporeal shock wave lithotripsy in the management of gallstone disease. Ann R Coll Surg Engl 1994; 76:42.
  2. Portincasa P, van de Meeberg P, van Erpecum KJ, et al. An update on the pathogenesis and treatment of cholesterol gallstones. Scand J Gastroenterol Suppl 1997; 223:60.
  3. Yamashita Y, Takada T, Kawarada Y, et al. Surgical treatment of patients with acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007; 14:91.
  4. Diehl AK. Epidemiology and natural history of gallstone disease. Gastroenterol Clin North Am 1991; 20:1.
  5. Attili AF, Carulli N, Roda E, et al. Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on Cholelithiasis (M.I.COL.). Am J Epidemiol 1995; 141:158.
  6. Attili AF, Capocaccia R, Carulli N, et al. Factors associated with gallstone disease in the MICOL experience. Multicenter Italian Study on Epidemiology of Cholelithiasis. Hepatology 1997; 26:809.
  7. Sherlock S, Dooley J. Diseases of the liver and biliary system, Blackwell Science, Oxford 2002.
  8. Trotman BW, Soloway RD. Pigment vs cholesterol cholelithiasis: clinical and epidemiological aspects. Am J Dig Dis 1975; 20:735.
  9. Ward A, Brogden RN, Heel RC, et al. Ursodeoxycholic acid: a review of its pharmacological properties and therapeutic efficacy. Drugs 1984; 27:95.
  10. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. part I. Dig Dis Sci 1982; 27:737.
  11. Bachrach WH, Hofmann AF. Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis. Part II. Dig Dis Sci 1982; 27:833.
  12. Fromm H, Malavolti M. Bile acid dissolution therapy of gallbladder stones. Baillieres Clin Gastroenterol 1992; 6:689.
  13. Peine CJ. Gallstone-dissolving agents. Gastroenterol Clin North Am 1992; 21:715.
  14. Rubin RA, Kowalski TE, Khandelwal M, Malet PF. Ursodiol for hepatobiliary disorders. Ann Intern Med 1994; 121:207.
  15. Guarino MP, Cong P, Cicala M, et al. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut 2007; 56:815.
  16. Hardison WG, Grundy SM. Effect of ursodeoxycholate and its taurine conjugate on bile acid synthesis and cholesterol absorption. Gastroenterology 1984; 87:130.
  17. Uchida K, Akiyoshi T, Igimi H, et al. Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice. Lipids 1991; 26:526.
  18. Wang DQ, Tazuma S, Cohen DE, Carey MC. Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse. Am J Physiol Gastrointest Liver Physiol 2003; 285:G494.
  19. van de Heijning BJ, van de Meeberg PC, Portincasa P, et al. Effects of ursodeoxycholic acid therapy on in vitro gallbladder contractility in patients with cholesterol gallstones. Dig Dis Sci 1999; 44:190.
  20. Bazzoli F, Festi D, Mazzella G, et al. Acquired gallstone opacification during cholelitholytic treatment with chenodeoxyholic, ursodeoxycholic, and tauroursodeoxycholic acids. Am J Gastroenterol 1995; 90:978.
  21. Tomida S, Abei M, Yamaguchi T, et al. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology 1999; 30:6.
  22. Paumgartner G, Pauletzki J, Sackmann M. Ursodeoxycholic acid treatment of cholesterol gallstone disease. Scand J Gastroenterol Suppl 1994; 204:27.
  23. Caroli A, Del Favero G, Di Mario F, et al. Computed tomography in predicting gall stone solubility: a prospective trial. Gut 1992; 33:698.
  24. Petroni ML, Jazrawi RP, Grundy A, et al. Prospective, multicenter study on value of computerized tomography (CT) in gallstone disease in predicting response to bile acid therapy. Dig Dis Sci 1995; 40:1956.
  25. Walters JR, Hood KA, Gleeson D, et al. Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy. Gut 1992; 33:375.
  26. Pereira SP, Veysey MJ, Kennedy C, et al. Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT scanning and reasons for nonresponse. Dig Dis Sci 1997; 42:1775.
  27. Malet PF, Baker J, Kahn MJ, Soloway RD. Gallstone composition in relation to buoyancy at oral cholecystography. Radiology 1990; 177:167.
  28. Dolgin SM, Schwartz JS, Kressel HY, et al. Identification of patients with cholesterol or pigment gallstones by discriminant analysis of radiographic features. N Engl J Med 1981; 304:808.
  29. Tangedahl T, Carey WD, Ferguson DR, et al. Drug and treatment efficacy of chenodeoxycholic acid in 97 patients with cholelithiasis and increased surgical risk. Dig Dis Sci 1983; 28:545.
  30. Maton PN, Iser JH, Reuben A, et al. Outcome of chenodeoxycholic acid (CDCA) treatment in 125 patients with radiolucent gallstones. Factors influencing efficacy, withdrawal, symptoms and side effects and post-dissolution recurrence. Medicine (Baltimore) 1982; 61:86.
  31. Tint GS, Salen G, Colalillo A, et al. Ursodeoxycholic acid: a safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med 1982; 97:351.
  32. Guarino MP, Cocca S, Altomare A, et al. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World J Gastroenterol 2013; 19:5029.
  33. Tudyka J, Kratzer W, Janowitz P, et al. Combined bile acid therapy is more effective on biliary lipids and dissolution rates than monotherapy after gallstone lithotripsy. Am J Gastroenterol 1995; 90:1942.
  34. May GR, Sutherland LR, Shaffer EA. Efficacy of bile acid therapy for gallstone dissolution: a meta-analysis of randomized trials. Aliment Pharmacol Ther 1993; 7:139.
  35. Jazrawi RP, Pigozzi MG, Galatola G, et al. Optimum bile acid treatment for rapid gall stone dissolution. Gut 1992; 33:381.
  36. Petroni ML, Jazrawi RP, Pazzi P, et al. Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group. Aliment Pharmacol Ther 2001; 15:123.
  37. Di Ciaula A, Wang DQ, Wang HH, et al. Targets for current pharmacologic therapy in cholesterol gallstone disease. Gastroenterol Clin North Am 2010; 39:245.
  38. Kupfer RM, Maudgal DP, Northfield TC. Gallstone dissolution rate during chenic acid therapy. Effect of bedtime administration plus low cholesterol diet. Dig Dis Sci 1982; 27:1025.
  39. Lanzini A, Facchinetti D, Northfield TC. Maintenance of hepatic bile acid secretion rate during overnight fasting by bedtime bile acid administration. Gastroenterology 1988; 95:1029.
  40. Senior JR, Johnson MF, DeTurck DM, et al. In vivo kinetics of radiolucent gallstone dissolution by oral dihydroxy bile acids. Gastroenterology 1990; 99:243.
  41. Bateson MC, Bouchier IA, Trash DB, et al. Calcification of radiolucent gall stone during treatment with ursodeoxycholic acid. Br Med J (Clin Res Ed) 1981; 283:645.
  42. Frigerio G. Ursodeoxycholic acid in the treatment of dyspepsia; Report of a multicenter controlled trial. Curr Ther Res 1979; 26:214.
  43. Venneman NG, Besselink MG, Keulemans YC, et al. Ursodeoxycholic acid exerts no beneficial effect in patients with symptomatic gallstones awaiting cholecystectomy. Hepatology 2006; 43:1276.
  44. Ertan A, Hernandez RE, Campeau RJ, et al. Extracorporeal shock-wave lithotripsy and ursodiol versus ursodiol alone in the treatment of gallstones. Gastroenterology 1992; 103:311.
  45. Ponchon T, Barkun AN, Pujol B, et al. Gallstone disappearance after extracorporeal lithotripsy and oral bile acid dissolution. Gastroenterology 1989; 97:457.
  46. Tint GS, Dyrszka H, Sanghavi B, et al. Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones. Gastroenterology 1992; 102:2042.
  47. Nicholl JP, Ross B, Milner PC, et al. Cost effectiveness of adjuvant bile salt treatment in extracorporeal shock wave lithotripsy for the treatment of gall bladder stones. Gut 1994; 35:1294.
  48. Saunders KD, Cates JA, Abedin MZ, Roslyn JJ. Lovastatin and gallstone dissolution: a preliminary study. Surgery 1993; 113:28.
  49. Chapman BA, Burt MJ, Chisholm RJ, et al. Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor. Dig Dis Sci 1998; 43:349.
  50. Kallien G, Lange K, Stange EF, Scheibner J. The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans. Hepatology 1999; 30:14.
  51. Duane WC. Effects of lovastatin and dietary cholesterol on bile acid kinetics and bile lipid composition in healthy male subjects. J Lipid Res 1994; 35:501.
  52. Hoogerbrugge-vd Linden N, de Rooy FW, Jansen H, van Blankenstein M. Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolaemia. Gut 1990; 31:348.
  53. Tazuma S, Takizawa I, Kunita T, et al. Effects of long-term treatment with low-dose pravastatin on biliary lipid and bile acid composition in patients with nonfamilial hyperlipoproteinemia. Metabolism 1995; 44:1410.
  54. Duane WC, Hunninghake DB, Freeman ML, et al. Simvastatin, a competitive inhibitor of HMG-CoA reductase, lowers cholesterol saturation index of gallbladder bile. Hepatology 1988; 8:1147.
  55. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Statin use and the risk of cholecystectomy in women. Gastroenterology 2009; 136:1593.
  56. Bodmer M, Brauchli YB, Krähenbühl S, et al. Statin use and risk of gallstone disease followed by cholecystectomy. JAMA 2009; 302:2001.
  57. González-Pérez A, García Rodríguez LA. Gallbladder disease in the general population: association with cardiovascular morbidity and therapy. Pharmacoepidemiol Drug Saf 2007; 16:524.
  58. Porsch-Ozçürümez M, Hardt PD, Schnell-Kretschmer H, et al. Effects of fluvastatin on biliary lipids in subjects with an elevated cholesterol saturation index. Eur J Clin Pharmacol 2001; 56:873.
  59. Smith JL, Roach PD, Wittenberg LN, et al. Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones. J Gastroenterol Hepatol 2000; 15:871.
  60. Wilson IR, Hurrell MA, Pattinson NR, Chapman BA. The effect of simvastatin and bezafibrate on bile composition and gall-bladder emptying in female non-insulin-dependent diabetics. J Gastroenterol Hepatol 1994; 9:447.
  61. Erichsen R, Frøslev T, Lash TL, et al. Long-term statin use and the risk of gallstone disease: A population-based case-control study. Am J Epidemiol 2011; 173:162.
  62. Smit JW, van Erpecum KJ, Renooij W, et al. The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease. Hepatology 1995; 21:1523.
  63. Sackmann M, Koelbl R, Pauletzki J, et al. Simvastatin added to ursodeoxycholic acid does not enhance disappearance of gallstone fragments after shock wave therapy. Z Gastroenterol 1995; 33:585.
  64. Caroli-Bosc FX, Le Gall P, Pugliese P, et al. Role of fibrates and HMG-CoA reductase inhibitors in gallstone formation: epidemiological study in an unselected population. Dig Dis Sci 2001; 46:540.
  65. Miettinen TE, Kiviluoto T, Taavitsainen M, et al. Cholesterol metabolism and serum and biliary noncholesterol sterols in gallstone patients during simvastatin and ursodeoxycholic acid treatments. Hepatology 1998; 27:649.
  66. Sharma BC, Agarwal DK, Baijal SS, Saraswat VA. Pravastatin has no effect on bile lipid composition, nucleation time, and gallbladder motility in persons with normal levels of cholesterol. J Clin Gastroenterol 1997; 25:433.
  67. Tazuma S, Kajiyama G, Mizuno T, et al. A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy. J Clin Gastroenterol 1998; 26:287.
  68. Wang HH, Portincasa P, Mendez-Sanchez N, et al. Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology 2008; 134:2101.
  69. de Bari O, Wang HH, Portincasa P, et al. Ezetimibe prevents the formation of oestrogen-induced cholesterol gallstones in mice. Eur J Clin Invest 2014; 44:1159.
  70. Doran J, Keighley MR, Bell GD. Rowachol–a possible treatment for cholesterol gallstones. Gut 1979; 20:312.
  71. Ellis WR, Somerville KW, Whitten BH, Bell GD. Pilot study of combination treatment for gall stones with medium dose chenodeoxycholic acid and a terpene preparation. Br Med J (Clin Res Ed) 1984; 289:153.
  72. Zakko S, Srb S. Chemical contact dissolution of cholesterol gallbladder stones. One hundred years later. Recenti Prog Med 1992; 83:416.
  73. vanSonnenberg E, Casola G, Varney RR, et al. Interventional radiology in the gallbladder. Radiographics 1989; 9:39.
  74. vanSonnenberg E, Casola G, Zakko SF, et al. Gallbladder and bile duct stones: percutaneous therapy with primary MTBE dissolution and mechanical methods. Radiology 1988; 169:505.
  75. Berger H, Forst H, Nattermann U, Pratschke E. [Percutaneous cholecystostomy in treating acute cholecystitis in patients at risk]. Rofo 1989; 150:694.
  76. Thistle JL, May GR, Bender CE, et al. Dissolution of cholesterol gallbladder stones by methyl tert-butyl ether administered by percutaneous transhepatic catheter. N Engl J Med 1989; 320:633.
  77. Zakko SF, Hofmann AF. Microprocessor-assisted solvent transfer system for effective contact dissolution of gallbladder stones. IEEE Trans Biomed Eng 1990; 37:410.
  78. Zakko SF, Hofmann AF. Microprocessor-assisted solvent-transfer system for gallstone dissolution. In vitro and in vivo validation. Gastroenterology 1990; 99:1807.
  79. Schoenfield LJ, Marks JW. Oral and contact dissolution of gallstones. Am J Surg 1993; 165:427.
  80. Hofmann AF, Amelsberg A, Esch O, et al. Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate. Dig Dis Sci 1997; 42:1274.
  81. Zakko SF, Scirica JC, Guttermuth MC, et al. Ethyl propionate is more effective and less cytotoxic than methyl tert-butyl ether for topical gallstone dissolution. Gastroenterology 1997; 113:232.
  82. Hofmann AF, Schteingart CD, vanSonnenberg E, et al. Contact dissolution of cholesterol gallstones with organic solvents. Gastroenterol Clin North Am 1991; 20:183.
  83. Zakko SF. Topical contact dissolution of gallbladder and biliary tract. In: Diseases of the gallbladder, Afdhal NH (Ed), NYC 2000.
  84. Palmer KR, Hofmann AF. Intraductal mono-octanoin for the direct dissolution of bile duct stones: experience in 343 patients. Gut 1986; 27:196.
  85. Lee LL, McGahan JP. Dissolution of cholesterol gallstones: comparison of solvents. Gastrointest Radiol 1986; 11:169.
  86. Davis CA, Landercasper J, Gundersen LH, Lambert PJ. Effective use of percutaneous cholecystostomy in high-risk surgical patients: techniques, tube management, and results. Arch Surg 1999; 134:727.
  87. Burhenne HJ, Stoller JL. Minicholecystostomy and radiologic stone extraction in high-risk cholelithiasis patients. Preliminary experience. Am J Surg 1985; 149:632.
  88. Zakko S. Diagnostic imaging before and after dissolution of gallbladder stones. Recenti Prog Med 1992; 83:407.
  89. Conway JD, Russo MW, Shrestha R. Endoscopic stent insertion into the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease. Gastrointest Endosc 2005; 61:32.
  90. Shrestha R, Trouillot TE, Everson GT. Endoscopic stenting of the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease awaiting orthotopic liver transplantation. Liver Transpl Surg 1999; 5:275.
  91. Shrestha R, Bilir BM, Everson GT, Steinberg SE. Endoscopic stenting of gallbladder for symptomatic cholelithiasis in patients with end-stage liver disease awaiting orthotopic liver transplantation. Am J Gastroenterol 1996; 91:595.
  92. Gaglio PJ, Buniak B, Leevy CB. Primary endoscopic retrograde cholecystoendoprosthesis: a nonsurgical modality for symptomatic cholelithiasis in cirrhotic patients. Gastrointest Endosc 1996; 44:339.
  93. Kalloo AN, Thuluvath PJ, Pasricha PJ. Treatment of high-risk patients with symptomatic cholelithiasis by endoscopic gallbladder stenting. Gastrointest Endosc 1994; 40:608.
  94. Schlenker C, Trotter JF, Shah RJ, et al. Endoscopic gallbladder stent placement for treatment of symptomatic cholelithiasis in patients with end-stage liver disease. Am J Gastroenterol 2006; 101:278.
  95. Sackmann M, Delius M, Sauerbruch T, et al. Shock-wave lithotripsy of gallbladder stones. The first 175 patients. N Engl J Med 1988; 318:393.
  96. T. Schöffmann; F.. Extracorporeal Shockwave Lithotripsy (Eswl) for the Treatment of Gallbladder Stones: Long-term Results after More than 20 Years. Hepato-Pancreato-Biliary 2016; 18:854e.
  97. Petroni ML, Jazrawi RP, Pazzi P, et al. Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group. Eur J Gastroenterol Hepatol 2000; 12:695.
  98. Portincasa P, van Erpecum KJ, van De Meeberg PC, et al. Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy. Hepatology 1996; 24:580.
  99. Lanzini A, Jazrawi RP, Kupfer RM, et al. Gallstone recurrence after medical dissolution. An overestimated threat? J Hepatol 1986; 3:241.
  100. Rabenstein T, Radespiel-Tröger M, Höpfner L, et al. Ten years experience with piezoelectric extracorporeal shockwave lithotripsy of gallbladder stones. Eur J Gastroenterol Hepatol 2005; 17:629.
  101. Sackmann M, Ippisch E, Sauerbruch T, et al. Early gallstone recurrence rate after successful shock-wave therapy. Gastroenterology 1990; 98:392.
  102. Villanova N, Bazzoli F, Taroni F, et al. Gallstone recurrence after successful oral bile acid treatment. A 12-year follow-up study and evaluation of long-term postdissolution treatment. Gastroenterology 1989; 97:726.
Print Friendly, PDF & Email