Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on modern management of frailty

LIVE: Thursday 17th October 2024, 18:00-19:30 (CEST)

Frailty has a significant impact on health and wellbeing, especially in older adults. Join our experts to understand the factors that contribute to the development of frailty and find out how to manage the condition and reduce the risk of disability, dependency, and mortality.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences

25-09-2024 | Crohn's Disease | Original Article

Risk Factors for Gallstones in Crohn’s Disease: A Systematic Review and Meta-Analysis

Authors: Yan Gong, Yishu He, Mengting Wan, Hong Chen

Published in: Digestive Diseases and Sciences

Login to get access

Abstract

Background

Crohn’s disease (CD) have an increased risk of gallstone disease. We aimed to systematically evaluate the prevalence rate and relevant risk factors of gallstones in CD patients.

Methods

A comprehensive search of PubMed, Embase, and Web of Science databases from inception to September 10, 2023, identified studies investigating risk factors for gallstone development among CD patients. Gender, age, body mass index, disease duration, disease site, stenosis, prior surgery, hospitalization times, corticosteroids, immunomodulators, and total parenteral nutrition (TPN) were assessed as potential risk factors. Odds ratios (OR) and confidence intervals (CI) were calculated.

Result

Among 1184 articles, 11 observational studies (3588 patients) were included. The prevalence of CD patients with gallstones was approximately 14.7%. Factors significantly associated with increased gallstone risk included Age ≥ 40 years old (OR 3.06, 95% CI 2.09- 4.48), disease duration > 15 years (OR 3.01, 95% CI 2.06–4.42), lifetime surgery(OR 2.50, 95% CI 1.99–3.12), disease located in ileocolon (OR 1.38, 95% CI 1.04–1.83) and ileocecal(OR 1.93, 95% CI 1.16–3.21), multiple hospitalizations(OR 4.26, 95% CI 2.43–7.46), corticosteroid treatments(OR 2.65, 95% CI 1.52–4.63), immunomodulator therapy(OR 1.94, 95% CI 1.12–3.38), and TPN use(OR 2.66, 95% CI 1.29–5.51). Sex, stenosis, overweight, or low weight did not significantly increase the risk of gallstone developing.

Conclusion

Age, long disease duration, specific disease locations (ileocolon, ileocecal), surgery, number of hospitalizations, corticosteroids, immunomodulator therapy, and TPN were identified as factors that increased the risk of gallstones in CD patients. About 14.7% of CD patients experience gallstones, so raising awareness and implementing prevention are needed.
Registration: PROSPERO (CRD42023449299).

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12:205–217.PubMedCrossRef
2.
Gg K, Jw W. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56–66.CrossRef
3.
4.
Gizard E, Ford AC, Bronowicki J-P et al. Systematic review: the epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2014;40:3–15.PubMedCrossRef
5.
Baig MMA, Irfan SA, Sumbal A et al. Prevalence of gallstones in ulcerative colitis and Crohn’s disease: a systematic review and meta-analysis. Cureus. 2022;14:e26121.PubMedPubMedCentral
6.
7.
Shabanzadeh DM. Incidence of gallstone disease and complications. Curr Opin Gastroenterol. 2018;34:81–89.PubMedCrossRef
8.
Bargiggia S, Maconi G, Elli M et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol. 2003;36:417–420.PubMedCrossRef
9.
Fagagnini S, Heinrich H, Rossel J-B et al. Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases. PLoS One. 2017;12:e0185193.PubMedPubMedCentralCrossRef
10.
Lapidus A, Bångstad M, Aström M et al. The prevalence of gallstone disease in a defined cohort of patients with Crohn’s disease. Am J Gastroenterol. 1999;94:1261–1266.PubMedCrossRef
11.
Lin J, Shen B, Lee H-J et al. Histopathological characterization of cholecystectomy specimens in patients with inflammatory bowel disease. J Crohns Colitis. 2012;6:895–899.PubMedCrossRef
12.
Saubermann LJ, Deneau M, Falcone RA et al. Hepatic issues and complications associated with inflammatory bowel disease: a clinical report from the naspghan inflammatory bowel disease and hepatology committees. J Pediatr Gastroenterol Nutr. 2017;64:639–652.PubMedCrossRef
13.
Fousekis FS, Katsanos KH, Theopistos VI et al. Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study. BMC Gastroenterol. 2019;19:48.PubMedPubMedCentralCrossRef
14.
La Meir M, Van Molhem Y. Recurrence of gallstone ileus with Crohn’s disease. Acta Chir Belg. 2001;101:35–37.PubMedCrossRef
15.
Koutroumpakis F, Lodhi M, Ahsan M et al. The impact of cholecystectomy on long-term disease outcomes and quality of life in patients with Crohn’s disease. Inflamm Bowel Dis. 2021;27:336–343.PubMedCrossRef
16.
Chew SSB, Ngo TQ, Douglas PR et al. Cholecystectomy in patients with Crohn’s ileitis. Dis Colon Rectum. 2003;46:1484–1488.PubMedCrossRef
17.
Goet JC, Beelen EMJ, Biermann KE et al. Cholecystectomy risk in Crohn’s disease patients after ileal resection: a long-term nationwide cohort study. J Gastrointest Surg. 2019;23:1840–1847.PubMedCrossRef
18.
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;161:2201–2204.PubMedCrossRef
19.
Kratzer W, Haenle M-M, Mason R-A et al. Prevalence of cholelithiasis in patients with chronic inflammatory bowel disease. World J Gastroenterol. 2005;11:6170–6175.PubMedPubMedCentralCrossRef
20.
Acosta MB, Dominguez-Munoz JE, de Nunez-Pardo Vera MC et al. Relationship between clinical features of Crohn’s disease and the risk of developing extraintestinal manifestations. Eur J Gastroenterol Hepatol. 2007;19:73–78.CrossRef
21.
Sturdik I, Krajcovicova A, Jalali Y et al. Pathophysiology and risk factors for cholelithiasis in patients with Crohn’s disease. Physiol Res. 2019;68:S173–S182.PubMedCrossRef
22.
23.
24.
Sterne JAC, Sutton AJ, Ioannidis JPA et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.PubMedCrossRef
25.
26.
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;45:1267–1274.PubMedCrossRef
27.
Repiso A, Alcántara M, Muñoz-Rosas C et al. Extraintestinal manifestations of Crohn’s disease: prevalence and related factors. Rev Esp Enferm Dig. 2006;98:510–517.PubMedCrossRef
28.
Lorusso D, Leo S, Mossa A et al. Cholelithiasis in inflammatory bowel disease: a case–control study. Dis Colon Rectum. 1990;33:791–794.PubMedCrossRef
29.
Silva J, Brito BS, de Silva INN et al. Frequency of hepatobiliary manifestations and concomitant liver disease in inflammatory bowel disease patients. Biomed Res Int. 2019;2019:7604939.PubMedPubMedCentralCrossRef
30.
Zhang FM, Xu CF, Shan GD et al. Is gallstone disease associated with inflammatory bowel diseases? A meta-analysis. J Dig Dis. 2015;16:634–641.PubMedCrossRef
31.
Johansson K, Sundström J, Marcus C et al. Risk of symptomatic gallstones and cholecystectomy after a very-low-calorie diet or low-calorie diet in a commercial weight loss program: 1-year matched cohort study. Int J Obes. 2014;38:279–284.CrossRef
32.
33.
Hsu H-Y, Huang C-Y, Hwang L-C. Sex difference of the predictive value of BMI, waist circumference and percentage body fat mass for gallstone disease. Br J Nutr. 2019;121:955–960.PubMedCrossRef
34.
Wen N, Wang Y, Cai Y, Nie G et al. Risk factors for recurrent common bile duct stones: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2023;17:937–947.PubMedCrossRef
35.
Song ST, Shi J, Wang XH et al. Prevalence and risk factors for gallstone disease: a population-based cross-sectional study. J Dig Dis. 2020;21:237–245.PubMedCrossRef
36.
Colvin HS, Kimura T, Iso H et al. Risk factors for gallstones and cholecystectomy: a large-scale population-based prospective cohort study in Japan. Dig Dis. 2022;40:385–393.PubMedCrossRef
37.
Damião AOMC, Sipahi AM, Vezozzo DP et al. Gallbladder hypokinesia in Crohn’s disease. Digestion. 1997;58:458–463.PubMedCrossRef
38.
Vu MK, Gielkens HA, van Hogezand RA et al. Gallbladder motility in Crohn disease: influence of disease localization and bowel resection. Scand J Gastroenterol. 2000;35:1157–1162.PubMedCrossRef
39.
Masclee AAM, Vu MK. Gallbladder motility in inflammatory bowel diseases. Dig Liver Dis. 2003;35:S35–S38.PubMedCrossRef
40.
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;116:1420–1427.PubMedCrossRef
41.
Vítek L, Carey MC. Enterohepatic cycling of bilirubin as a cause of ‘black’ pigment gallstones in adult life. Eur J Clin Invest. 2003;33:799–810.PubMedCrossRef
42.
Pereira SP, Bain IM, Kumar D et al. Bile composition in inflammatory bowel disease: ileal disease and colectomy, but not colitis, induce lithogenic bile. Aliment Pharmacol Ther. 2003;17:923–933.PubMedCrossRef
43.
Brink M, MendezSanchez N, Carey M. Bilirubin cycles enterohepatically after ileal resection in the rat. Gastroenterology. 1996;110:1945–1957.PubMedCrossRef
44.
45.
46.
Keulemans YCA, Mok KS, Slors JFM et al. Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn’s disease compared to patients with ulcerative colitis. J Hepatol. 1999;31:685–691.PubMedCrossRef
47.
Maurer P, Haag K, Roth M et al. No evidence for abnormal gallbladder emptying in Crohn’s disease. Hepatogastroenterology. 1996;43:807–812.PubMed
48.
49.
Pringle PL, Stewart KO, Peloquin JM et al. Body mass index, genetic susceptibility, and risk of complications among individuals with Crohn’s disease. Inflamm Bowel Dis. 2015;21:2304–2310.PubMed
50.
Nic Suibhne T, Raftery TC, McMahon O et al. High prevalence of overweight and obesity in adults with Crohn’s disease: associations with disease and lifestyle factors. J Crohn’s Colitis. 2013;7:e241–e248.CrossRef
51.
52.
53.
Greuter T, Porchet F, Braga-Neto MB et al. Impact of obesity on disease activity and disease outcome in inflammatory bowel disease: results from the Swiss inflammatory bowel disease cohort. UEG J. 2020;8:1196–1207.CrossRef
54.
55.
Cohen S, Kpplan M, Gottlieb L et al. Liver disease and gallstones in regional enteritis. Gastroenterology. 1971;60:237–245.PubMedCrossRef
56.
57.
Peyrin-Biroulet L. Is ileocaecal Crohn’s disease L1 or L3 according to the Montreal classification? Gut. 2008;57:427–427.PubMedCrossRef
58.
Lapidus A, Einarsson C. Bile composition in patients with ileal resection due to Crohn’s disease. Inflamm Bowel Dis. 1998;4:89–94.PubMedCrossRef
59.
Holzer A, Harsch S, Renner O et al. Diminished expression of apical sodium-dependent bile acid transporter in gallstone disease is independent of ileal inflammation. Digestion. 2008;78:52–59.PubMedCrossRef
60.
Navaneethan U, Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16:1598–1619.PubMedCrossRef
61.
Pitt HA, King W 3rd, Mann LL et al. Increased risk of cholelithiasis with prolonged total parenteral nutrition. Am J Surg. 1983;145:106–112.PubMedCrossRef
62.
Greuter T, Vavricka SR. Extraintestinal manifestations in inflammatory bowel disease—epidemiology, genetics, and pathogenesis. Expert Rev Gastroenterol Hepatol. 2019;13:307–317.PubMedCrossRef
63.
64.
65.
66.
Messing B, Bories C, Kunstlinger F, Bernier J-J. Does total parenteral nutrition induce gallbladder sludge formation and lithiasis? Gastroenterology. 1983;84:1012–1019.PubMedCrossRef
67.
68.
Angelico M, Guardia PD. Review article: hepatobiliary complications associated with total parenteral nutrition. Aliment Pharmacol Ther. 2000;14:54–57.PubMedCrossRef
69.
Muller EL, Grace PA, Pitt HA. The effect of parenteral nutrition on biliary calcium and bilirubin. J Surg Res. 1986;40:55–62.PubMedCrossRef
70.
Shiloni E, Coronado E, Freund HR. Role of total parenteral nutrition in the treatment of Crohn’s disease. Am J Surg. 1989;157:180–185.PubMedCrossRef
71.
Triantafillidis JK, Papalois AE. The role of total parenteral nutrition in inflammatory bowel disease: current aspects. Scand J Gastroenterol. 2013;49:3–14.CrossRef
72.
73.
Kucharski MA, Wierzbicka A, Tsibulski A et al. Parenteral and enteral nutrition: a bridge to healing and biological therapy in a patient with enterocutaneous fistula and sepsis complicated Crohn’s disease. J Parenter Enteral Nutr. 2021;45:430–433.CrossRef
74.
Zittan E, Gralnek IM, Hatoum OA et al. Preoperative exclusive total parental nutrition is associated with clinical and laboratory remission in severe active Crohn’s disease—a pilot study. Nutrients. 2020;12:1244.PubMedPubMedCentralCrossRef
75.
McNeice A, Scott R, Rafferty GP et al. The hepatobiliary complications of malnutrition and nutritional support in adults. Ir J Med Sci. 2019;188:109–117.PubMedCrossRef
76.
Thompson J. The role of prophylactic cholecystectomy in the short-bowel syndrome. Arch Surg. 1996;131:556–559.PubMedCrossRef
77.
Appleton ND, Lal S, Carlson GL et al. Cholelithiasis and related morbidity in chronic intestinal failure: a longitudinal cohort study from a National Specialized Centre. J Gastrointest Surg. 2019;23:2002–2006.PubMedCrossRef
78.
Portincasa P, Di Ciaula A, de Bari O, Garruti G, Palmieri VO, Wang DQ-H. Management of gallstones and its related complications. Expert Rev Gastroenterol Hepatol. 2016;10:93–112.PubMedCrossRef
79.
Choi JH, Lee SH, Cho IR, Paik WH, Ryu JK, Kim Y-T. Ursodeoxycholic acid for the prevention of gallstone and subsequent cholecystectomy following gastric surgery: a systematic review and meta-analysis. J Hepatobiliary Pancreat Sci. 2021;28:409–418.PubMedCrossRef
80.
Venneman NG, van Erpecum KJ. Gallstone disease: primary and secondary prevention. Best Pract Res Clin Gastroenterol. 2006;20:1063–1073.PubMedCrossRef
81.
Mulliri A, Menahem B, Alves A et al. Ursodeoxycholic acid for the prevention of gallstones and subsequent cholecystectomy after bariatric surgery: a meta-analysis of randomized controlled trials. J Gastroenterol. 2022;57:529–539.PubMedCrossRef
Metadata
Title
Risk Factors for Gallstones in Crohn’s Disease: A Systematic Review and Meta-Analysis
Authors
Yan Gong
Yishu He
Mengting Wan
Hong Chen
Publication date
25-09-2024
Publisher
Springer US
Published in
Digestive Diseases and Sciences
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-024-08597-1

EASD 2024

‘Noninferior’ reduction of type 1 diabetes HbA1c by weekly insulin efsitora alfa

Weekly treatment with insulin efsitora is noninferior to daily insulin degludec for the reduction of HbA1c in adults with type 1 diabetes, show the findings of the QWINT-5 trial.

Read more

Weight loss with new obesity drug amycretin

Tirzepatide significantly reduces UACR in individuals with obesity and type 2 diabetes

Liraglutide reduces BMI for young children with obesity

» View more highlights on the EASD 2024 hub page

2024 ESC Congress

Noise pollution dangerous for heart health

Two studies underscore the adverse impact of noise pollution on the risk for and prognosis after myocardial infarction.

Read more

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more
Image Credits