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Epidemiology of and risk factors for gallstones

Nezam H Afdhal, MD, FRCPI
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Gallstone disease is one of the most common and costly of all digestive diseases. The third National Health and Nutrition Examination Survey estimated that 6.3 million men and 14.2 million women aged 20 to 74 in the United States had gallbladder disease [1].

Over the past two decades, a great deal has been learned about the epidemiology of and risk factors for gallstones (table 1). Ultrasonography has played a major role in this process, providing a rapid, risk-free method of screening large populations. Prior to the availability of ultrasound, most studies relied on highly selective autopsy data and limited oral cholecystography.


Epidemiologic data are available from a number of large European and American populations (table 2). These studies have revealed a marked variation in overall gallstone prevalence between different ethnic populations. As a general rule, there appears to be higher rates of cholelithiasis in Western Caucasian, Hispanic, and Native American populations and lower rates in Eastern European, African American, and Japanese populations [2-18].

In the United States, the age standardized prevalence of gallbladder disease was estimated based upon a sample of more than 14,000 persons aged 20 to 74 in whom gallbladder disease was detected by the presence of gallstones or cholecystectomy on ultrasonography [1]. The following prevalence rates were observed:

8.6 and 16.6 percent among non-Hispanic white men and women, respectively

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Literature review current through: Oct 2017. | This topic last updated: Nov 28, 2016.
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  1. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology 1999; 117:632.
  2. TORVIK A, HOIVIK B. Gallstones in an autopsy series. Incidence, complications, and correlations with carcinoma of the gallbladder. Acta Chir Scand 1960; 120:168.
  3. Zahor A, Sternby NH, Kagan A, et al. Frequency of cholelithiasis in Prague and Malmö. An autopsy study. Scand J Gastroenterol 1974; 9:3.
  4. Brett M, Barker DJ. The world distribution of gallstones. Int J Epidemiol 1976; 5:335.
  5. Lindström CG. Frequency of gallstone disease in a well-defined Swedish population. A prospective necropsy study in Malmö. Scand J Gastroenterol 1977; 12:341.
  6. Heaton KW, Braddon FE, Mountford RA, et al. Symptomatic and silent gall stones in the community. Gut 1991; 32:316.
  7. Maurer KR, Everhart JE, Ezzati TM, et al. Prevalence of gallstone disease in Hispanic populations in the United States. Gastroenterology 1989; 96:487.
  8. Sampliner RE, Bennett PH, Comess LJ, et al. Gallbladder disease in pima indians. Demonstration of high prevalence and early onset by cholecystography. N Engl J Med 1970; 283:1358.
  9. Thistle JL, Eckhart KL Jr, Nensel RE, et al. Prevalence of gallbladder disease among Chippewa Indians. Mayo Clin Proc 1971; 46:603.
  10. Williams CN, Johnston JL, Weldon KL. Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women. Can Med Assoc J 1977; 117:758.
  11. WILBUR RS, BOLT RJ. Incidence of gall bladder disease in normal men. Gastroenterology 1959; 36:251.
  12. Williams CN, Johnston JL. Prevalence of gallstones and risk factors in Caucasian women in a rural Canadian community. Can Med Assoc J 1980; 122:664.
  13. 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.
  14. Barbara L, Sama C, Morselli-Labate AM, et al. A ten year incidence of gallstone disease: The Sirmione study. J Hepatol 1993; 18(Suppl 1):S43.
  15. CUNNINGHAM JA, HARDENBERGH FE. Comparative incidence of choletithiasis in the Negro and white races; a study of 6185 autopsies. AMA Arch Intern Med 1956; 97:68.
  16. NEWMAN HF, NORTHUP JD. The autopsy incidence of gallstones. Surg Gynecol Obstet 1959; 109:1.
  17. Sichieri R, Everhart JE, Roth HP. Low incidence of hospitalization with gallbladder disease among blacks in the United States. Am J Epidemiol 1990; 131:826.
  18. Nomura H, Kashiwagi S, Hayashi J, et al. Prevalence of gallstone disease in a general population of Okinawa, Japan. Am J Epidemiol 1988; 128:598.
  19. Everhart JE, Yeh F, Lee ET, et al. Prevalence of gallbladder disease in American Indian populations: findings from the Strong Heart Study. Hepatology 2002; 35:1507.
  20. The epidemiology of gallstone disease in Rome, Italy. Part I. Prevalence data in men. The Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO). Hepatology 1988; 8:904.
  21. Valdivieso V, Covarrubias C, Siegel F, Cruz F. Pregnancy and cholelithiasis: pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 1993; 17:1.
  22. Maringhini A, Ciambra M, Baccelliere P, et al. Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history. Ann Intern Med 1993; 119:116.
  23. Everson GT. Pregnancy and gallstones. Hepatology 1993; 17:159.
  24. Kern F Jr, Everson GT, DeMark B, et al. Biliary lipids, bile acids, and gallbladder function in the human female. Effects of pregnancy and the ovulatory cycle. J Clin Invest 1981; 68:1229.
  25. Honoré LH. Increased incidence of symptomatic cholesterol cholelithiasis in perimenopausal women receiving estrogen replacement therapy: a retrospective study. J Reprod Med 1980; 25:187.
  26. Grodstein F, Colditz GA, Stampfer MJ. Postmenopausal hormone use and cholecystectomy in a large prospective study. Obstet Gynecol 1994; 83:5.
  27. Henriksson P, Einarsson K, Eriksson A, et al. Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. J Clin Invest 1989; 84:811.
  28. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280:605.
  29. Racine A, Bijon A, Fournier A, et al. Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort. CMAJ 2013; 185:555.
  30. Cirillo DJ, Wallace RB, Rodabough RJ, et al. Effect of estrogen therapy on gallbladder disease. JAMA 2005; 293:330.
  31. Liu B, Beral V, Balkwill A, et al. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ 2008; 337:a386.
  32. Coronary Drug Project Research Group. Gallbladder disease as a side effect of drugs influencing lipid metabolism. Experience in the Coronary Drug Project. N Engl J Med 1977; 296:1185.
  33. Strom BL, Tamragouri RN, Morse ML, et al. Oral contraceptives and other risk factors for gallbladder disease. Clin Pharmacol Ther 1986; 39:335.
  34. Scragg RK, McMichael AJ, Seamark RF. Oral contraceptives, pregnancy, and endogenous oestrogen in gall stone disease--a case-control study. Br Med J (Clin Res Ed) 1984; 288:1795.
  35. Thijs C, Leffers P, Knipschild P. Oral contraceptive use and the occurrence of gallstone disease--a case-control study. Prev Med 1993; 22:122.
  36. Thijs C, Knipschild P. Oral contraceptives and the risk of gallbladder disease: a meta-analysis. Am J Public Health 1993; 83:1113.
  37. Gilat T, Feldman C, Halpern Z, et al. An increased familial frequency of gallstones. Gastroenterology 1983; 84:242.
  38. Sarin SK, Negi VS, Dewan R, et al. High familial prevalence of gallstones in the first-degree relatives of gallstone patients. Hepatology 1995; 22:138.
  39. Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N Engl J Med 1999; 341:427.
  40. Friedman GD, Kannel WB, Dawber TR. The epidemiology of gallbladder disease: observations in the Framingham Study. J Chronic Dis 1966; 19:273.
  41. Mabee TM, Meyer P, DenBesten L, Mason EE. The mechanism of increased gallstone formation in obese human subjects. Surgery 1976; 79:460.
  42. Stampfer MJ, Maclure KM, Colditz GA, et al. Risk of symptomatic gallstones in women with severe obesity. Am J Clin Nutr 1992; 55:652.
  43. Scragg RK, McMichael AJ, Baghurst PA. Diet, alcohol, and relative weight in gall stone disease: a case-control study. Br Med J (Clin Res Ed) 1984; 288:1113.
  44. Jørgensen T. Prevalence of gallstones in a Danish population. Am J Epidemiol 1987; 126:912.
  45. Amaral JF, Thompson WR. Gallbladder disease in the morbidly obese. Am J Surg 1985; 149:551.
  46. Liddle RA, Goldstein RB, Saxton J. Gallstone formation during weight-reduction dieting. Arch Intern Med 1989; 149:1750.
  47. Broomfield PH, Chopra R, Sheinbaum RC, et al. Effects of ursodeoxycholic acid and aspirin on the formation of lithogenic bile and gallstones during loss of weight. N Engl J Med 1988; 319:1567.
  48. Shiffman ML, Kaplan GD, Brinkman-Kaplan V, Vickers FF. Prophylaxis against gallstone formation with ursodeoxycholic acid in patients participating in a very-low-calorie diet program. Ann Intern Med 1995; 122:899.
  49. Shiffman ML, Sugerman HJ, Kellum JM, Moore EW. Changes in gallbladder bile composition following gallstone formation and weight reduction. Gastroenterology 1992; 103:214.
  50. De Santis A, Attili AF, Ginanni Corradini S, et al. Gallstones and diabetes: a case-control study in a free-living population sample. Hepatology 1997; 25:787.
  51. Chapman BA, Wilson IR, Frampton CM, et al. Prevalence of gallbladder disease in diabetes mellitus. Dig Dis Sci 1996; 41:2222.
  52. Ruhl CE, Everhart JE. Association of diabetes, serum insulin, and C-peptide with gallbladder disease. Hepatology 2000; 31:299.
  53. Biddinger SB, Haas JT, Yu BB, et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 2008; 14:778.
  54. Hahm JS, Park JY, Park KG, et al. Gallbladder motility in diabetes mellitus using real time ultrasonography. Am J Gastroenterol 1996; 91:2391.
  55. Thijs C, Knipschild P, Brombacher P. Serum lipids and gallstones: a case-control study. Gastroenterology 1990; 99:843.
  56. Scragg RK, Calvert GD, Oliver JR. Plasma lipids and insulin in gall stone disease: a case-control study. Br Med J (Clin Res Ed) 1984; 289:521.
  57. Halldestam I, Kullman E, Borch K. Incidence of and potential risk factors for gallstone disease in a general population sample. Br J Surg 2009; 96:1315.
  58. Marks JW, Cleary PA, Albers JJ. Lack of correlation between serum lipoproteins and biliary cholesterol saturation in patients with gallstones. Dig Dis Sci 1984; 29:1118.
  59. Stender S, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A. Extreme bilirubin levels as a causal risk factor for symptomatic gallstone disease. JAMA Intern Med 2013; 173:1222.
  60. Conte D, Fraquelli M, Fornari F, et al. Close relation between cirrhosis and gallstones: cross-sectional and longitudinal survey. Arch Intern Med 1999; 159:49.
  61. Alvaro D, Angelico M, Gandin C, et al. Physico-chemical factors predisposing to pigment gallstone formation in liver cirrhosis. J Hepatol 1990; 10:228.
  62. Stauber RE, Rosenblum E, Eagon PK, et al. The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats. Gastroenterology 1991; 100:168.
  63. Acalovschi M, Dumitraşcu DL, Csakany I. Gastric and gall bladder emptying of a mixed meal are not coordinated in liver cirrhosis--a simultaneous sonographic study. Gut 1997; 40:412.
  64. Apstein MD, Dalecki-Chipperfield K. Spinal cord injury is a risk factor for gallstone disease. Gastroenterology 1987; 92:966.
  65. Quigley EM, Marsh MN, Shaffer JL, Markin RS. Hepatobiliary complications of total parenteral nutrition. Gastroenterology 1993; 104:286.
  66. Nightingale JM, Lennard-Jones JE, Gertner DJ, et al. Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gall stones in patients with a short bowel. Gut 1992; 33:1493.
  67. Hussaini SH, Murphy GM, Kennedy C, et al. The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones. Gastroenterology 1994; 107:1503.
  68. Ezzat S, Snyder PJ, Young WF, et al. Octreotide treatment of acromegaly. A randomized, multicenter study. Ann Intern Med 1992; 117:711.
  69. Newman CB, Melmed S, Snyder PJ, et al. Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study. J Clin Endocrinol Metab 1995; 80:2768.
  70. 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.
  71. Ståhlberg D, Reihnér E, Rudling M, et al. Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7 alpha-hydroxylase. Hepatology 1995; 21:1025.
  72. Teramoto T, Abe K, Taneyama T. Safety and efficacy of long-term combination therapy with bezafibrate and ezetimibe in patients with dyslipidemia in the prospective, observational J-COMPATIBLE study. Cardiovasc Diabetol 2013; 12:163.
  73. Arvidsson A, Alván G, Angelin B, et al. Ceftriaxone: renal and biliary excretion and effect on the colon microflora. J Antimicrob Chemother 1982; 10:207.
  74. Shiffman ML, Keith FB, Moore EW. Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. Gastroenterology 1990; 99:1772.
  75. Leitzmann MF, Giovannucci EL, Rimm EB, et al. The relation of physical activity to risk for symptomatic gallstone disease in men. Ann Intern Med 1998; 128:417.
  76. Leitzmann MF, Rimm EB, Willett WC, et al. Recreational physical activity and the risk of cholecystectomy in women. N Engl J Med 1999; 341:777.
  77. Lapidus A, Bångstad M, Aström M, Muhrbeck O. The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease. Am J Gastroenterol 1999; 94:1261.
  78. Brink MA, Slors JF, Keulemans YC, et al. Enterohepatic cycling of bilirubin: a putative mechanism for pigment gallstone formation in ileal Crohn's disease. Gastroenterology 1999; 116:1420.
  79. Fraquelli M, Losco A, Visentin S, et al. Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases. Arch Intern Med 2001; 161:2201.
  80. Parente F, Pastore L, Bargiggia S, et al. Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study. Hepatology 2007; 45:1267.
  81. Bodmer M, Brauchli YB, Krähenbühl S, et al. Statin use and risk of gallstone disease followed by cholecystectomy. JAMA 2009; 302:2001.
  82. 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.
  83. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III). Arch Intern Med 2000; 160:931.
  84. Zhang YP, Li WQ, Sun YL, et al. Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease. Aliment Pharmacol Ther 2015; 42:637.
  85. Leitzmann MF, Willett WC, Rimm EB, et al. A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men. JAMA 1999; 281:2106.
  86. Leitzmann MF, Stampfer MJ, Willett WC, et al. Coffee intake is associated with lower risk of symptomatic gallstone disease in women. Gastroenterology 2002; 123:1823.
  87. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Fruit and vegetable consumption and risk of cholecystectomy in women. Am J Med 2006; 119:760.
  88. Tsai CJ, Leitzmann MF, Hu FB, et al. A prospective cohort study of nut consumption and the risk of gallstone disease in men. Am J Epidemiol 2004; 160:961.
  89. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. The effect of long-term intake of cis unsaturated fats on the risk for gallstone disease in men: a prospective cohort study. Ann Intern Med 2004; 141:514.