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Ursodeoxycholic acid for the prevention of gallstones and subsequent cholecystectomy after bariatric surgery: a meta-analysis of randomized controlled trials

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Abstract

Background

This meta-analysis aimed to compare the incidence of gallstone formation, subsequent biliary disease and the need for cholecystectomy in untreated patients and patients treated with ursodeoxycholic acid (UDCA) following bariatric surgery.

Methods

Randomized controlled trials (RCTs) comparing UDCA and controls for the prevention of gallstone formation after bariatric surgery published until February 2022 were selected and subjected to a systematic review and meta-analysis. Articles were searched in the MEDLINE, Web of Science and Cochrane Trials Register databases. Meta-analysis was performed with Review Manager 5.0.

Results

Eleven randomized controlled studies were included, with a total of 2363 randomized patients and 2217 patients analysed in the UDCA group versus 1415 randomized patients and 1257 patients analysed in the control group. Considering analysed patients, prophylactic use of UDCA was significantly associated with decreased (i) gallstone formation (OR = 0.25, 95% CI = 0.21–0.31), (ii) symptomatic gallstone disease (GD) (OR = 0.29, 95% CI = 0.20–0.42) and consequently (iii) cholecystectomy rate (OR = 0.33, 95% CI = 0.20–0.55). The results were similar in ITT analysis, in the subgroup of patients undergoing sleeve gastrectomy or considering only randomized versus placebo studies.

Conclusions

Prophylactic use of UDCA after bariatric surgery prevents both gallstone formation and symptomatic GD and reduces the need for cholecystectomy.

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References

  1. Aerts R, Penninckx F. The burden of gallstone disease in Europe. Aliment Pharmacol Ther. 2003;18(Suppl 3):49–53.

    Article  Google Scholar 

  2. Stampfer MJ, Maclure KM, Colditz GA, et al. Risk of symptomatic gallstones in women with severe obesity. Am J Clin Nutr. 1992;55:652–8.

    Article  CAS  Google Scholar 

  3. Go AS, Mozaffarian D, Roger VL, et al. Executive summary: heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation. 2013;127:143–52.

    Article  Google Scholar 

  4. Weinsier RL, Ullmann DO. Gallstone formation and weight loss. Obes Res. 1993;1:51–6.

    Article  CAS  Google Scholar 

  5. Yang H, Petersen GM, Roth MP, et al. Risk factors for gallstone formation during rapid loss of weight. Dig Dis Sci. 1992;37:912–8.

    Article  CAS  Google Scholar 

  6. Sugerman HJ, Brewer WH, Shiffman ML, et al. A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss. Am J Surg. 1995;169:91–6.

    Article  CAS  Google Scholar 

  7. Worobetz LJ, Inglis FG, Shaffer EA. The effect of ursodeoxycholic acid therapy on gallstone formation in the morbidly obese during rapid weight loss. Am J Gastroenterol. 1993;88:1705–10.

    CAS  PubMed  Google Scholar 

  8. Worni M, Guller U, Shah A, et al. Cholecystectomy concomitant with laparoscopic gastric bypass: a trend analysis of the nationwide inpatient sample from 2001 to 2008. Obes Surg. 2012;22:220–9.

    Article  Google Scholar 

  9. Nabil TM, Khalil AH, Gamal K. Effect of oral ursodeoxycholic acid on cholelithiasis following laparoscopic sleeve gastrectomy for morbid obesity. Surg Obes Relat Dis. 2019;15:827–31.

    Article  Google Scholar 

  10. Pizza F, D’Antonio D, Lucido FS, et al. The role of Ursodeoxycholic acid (UDCA) in Cholelithiasis management after One Anastomosis Gastric Bypass (OAGB) for morbid obesity: results of a monocentric randomized controlled trial. Obes Surg. 2020;30:4315–24.

    Article  Google Scholar 

  11. Sakran N, Dar R, Assalia A, et al. The use of Ursolit for gallstone prophylaxis following bariatric surgery: a randomized-controlled trial. Updates Surg. 2020;72:1125–33.

    Article  Google Scholar 

  12. Talha A, Abdelbaki T, Farouk A, et al. Cholelithiasis after bariatric surgery, incidence, and prophylaxis: randomized controlled trial. Surg Endosc. 2020;34:5331–7.

    Article  Google Scholar 

  13. Williams C, Gowan R, Perey BJ. A double-blind placebo-controlled trial of ursodeoxycholic acid in the prevention of gallstones during weight loss after vertical banded gastroplasty. Obes Surg. 1993;3:257–9.

    Article  CAS  Google Scholar 

  14. Wudel LJ Jr, Wright JK, Debelak JP, et al. Prevention of gallstone formation in morbidly obese patients undergoing rapid weight loss: results of a randomized controlled pilot study. J Surg Res. 2002;102:50–6.

    Article  CAS  Google Scholar 

  15. Choi JH, Lee SH, Cho IR, et al. Ursodeoxycholic acid for the prevention of gallstone and subsequent cholecystectomy following gastric surgery: a systematic review and meta-analysis. J Hepatobiliary Pancreat Sci. 2021;28:409–18.

    Article  Google Scholar 

  16. Magouliotis DE, Tasiopoulou VS, Svokos AA, et al. Ursodeoxycholic acid in the prevention of gallstone formation after bariatric surgery: an updated systematic review and meta-analysis. Obes Surg. 2017;27:3021–30.

    Article  Google Scholar 

  17. Stokes CS, Gluud LL, Casper M, et al. Ursodeoxycholic acid and diets higher in fat prevent gallbladder stones during weight loss: a meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2014;12:1090–100.

    Article  CAS  Google Scholar 

  18. Fearon NM, Kearns EC, Kennedy CA, et al. The impact of ursodeoxycholic acid on gallstone disease after bariatric surgery: a meta-analysis of randomized control trials. Surg Obes Relat Dis. 2022;18:77–84.

    Article  Google Scholar 

  19. Haal S, Guman MSS, Boerlage TCC, et al. Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial. Lancet Gastroenterol Hepatol. 2021;6:993–1001.

    Article  Google Scholar 

  20. Salman MA, Salman A, Mohamed US, et al. Ursodeoxycholic acid for the prevention of gall stones after laparoscopic sleeve gastrectomy: a prospective controlled study. Surg Endosc. 2022. https://doi.org/10.1007/s00464-021-08980-3.

    Article  PubMed  Google Scholar 

  21. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  Google Scholar 

  22. Higgins JP, Altman DG, Gotzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  Google Scholar 

  23. Abdallah E, Emile SH, Elfeki H, et al. Role of ursodeoxycholic acid in the prevention of gallstone formation after laparoscopic sleeve gastrectomy. Surg Today. 2017;47:844–50.

    Article  CAS  Google Scholar 

  24. Alimogullari M, Bulus H. Effectiveness of ursodeoxycholic acid treatment in the prevention of gallstone formation after laparoscopic sleeve gastrectomy. Acta Chir Belg. 2021;121:109–14.

    Article  Google Scholar 

  25. Coupaye M, Calabrese D, Sami O, et al. Evaluation of incidence of cholelithiasis after bariatric surgery in subjects treated or not treated with ursodeoxycholic acid. Surg Obes Relat Dis. 2017;13:681–5.

    Article  Google Scholar 

  26. Coupaye M, Calabrese D, Sami O, et al. Effectiveness of ursodeoxycholic acid in the prevention of cholelithiasis after sleeve gastrectomy. Obes Surg. 2019;29:2464–9.

    Article  Google Scholar 

  27. Della Penna A, Lange J, Hilbert J, et al. Ursodeoxycholic acid for 6 months after bariatric surgery is impacting gallstone associated morbidity in patients with preoperative asymptomatic gallstones. Obes Surg. 2019;29:1216–21.

    Article  Google Scholar 

  28. Machado FHF, Castro Filho HF, Babadopulos R, et al. Ursodeoxycholic acid in the prevention of gallstones in patients subjected to Roux-en-Y gastric bypass1. Acta Cir Bras. 2019;34:e20190010000009.

    Article  Google Scholar 

  29. Sen O, Turkcapar AG, Yerdel MA. Cholelithiasis after sleeve gastrectomy and effectiveness of ursodeoxycholic acid treatment. J Laparoendosc Adv Surg Tech A. 2020;30:1150–2.

    Article  Google Scholar 

  30. Vural A, Goksu K, Kahraman AN, et al. Increased gallstone formation after sleeve gastrectomy and the preventive role of ursodeoxycholic acid. Acta Gastroenterol Belg. 2020;83:33–8.

    CAS  PubMed  Google Scholar 

  31. Ul Hassan M, Akram MA, Javaid I, et al. Role of ursodeoxycholic acid in prevention of gallstones after sleeve gastrectomy. Pak J Med Health Sci. 2021;15:666–8.

    Google Scholar 

  32. Adams LB, Chang C, Pope J, et al. Randomized, prospective comparison of ursodeoxycholic acid for the prevention of gallstones after sleeve gastrectomy. Obes Surg. 2016;26:990–4.

    Article  Google Scholar 

  33. Miller K, Hell E, Lang B, et al. Gallstone formation prophylaxis after gastric restrictive procedures for weight loss: a randomized double-blind placebo-controlled trial. Ann Surg. 2003;238:697–702.

    Article  Google Scholar 

  34. Abouzeid TAO, Shoka AAA. Should we prescribe ursodeoxycholic acid after laparoscopic sleeve gastrectomy? A two-center prospective randomized controlled trial. Egypt J Surg. 2018;37:349–54.

    Article  Google Scholar 

  35. Weinsier RL, Wilson LJ, Lee J. Medically safe rate of weight loss for the treatment of obesity: a guideline based on risk of gallstone formation. Am J Med. 1995;98:115–7.

    Article  CAS  Google Scholar 

  36. Douglas IJ, Bhaskaran K, Batterham RL, et al. Bariatric surgery in the United Kingdom: a cohort study of weight loss and clinical outcomes in routine clinical care. PLoS Med. 2015;12:e1001925.

    Article  Google Scholar 

  37. Everhart JE, Khare M, Hill M, et al. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999;117:632–9.

    Article  CAS  Google Scholar 

  38. Hong S, Qiwen B, Ying J, et al. Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis. Eur J Gastroenterol Hepatol. 2011;23:1136–43.

    Article  Google Scholar 

  39. Sneineh MA, Harel L, Elnasasra A, et al. Increased incidence of symptomatic cholelithiasis after bariatric roux-En-Y gastric bypass and previous bariatric surgery: a single center experience. Obes Surg. 2020;30:846–50.

    Article  Google Scholar 

  40. Anveden A, Peltonen M, Naslund I, et al. Long-term incidence of gallstone disease after bariatric surgery: results from the nonrandomized controlled Swedish Obese Subjects study. Surg Obes Relat Dis. 2020;16:1474–82.

    Article  Google Scholar 

  41. Haal S, Guman MSS, Bruin S, et al. Risk factors for symptomatic gallstone disease and gallstone formation after bariatric surgery. Obes Surg. 2022;32:1270–8.

    Article  Google Scholar 

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Authors and Affiliations

  1. Service de Chirurgie Digestive, CHU de Caen Normandie, Normandie Univ, UNICAEN, 14000, CAEN, France

    Andrea Mulliri, Benjamin Menahem & Arnaud Alves

  2. ‘Cancers and Preventions’, Team Labeled ‘League Against Cancer’, U1086 INSERM-UCBN, 3 avenue du Général Harris, 14000, CAEN, France

    Andrea Mulliri, Benjamin Menahem, Arnaud Alves & Benoît Dupont

  3. UFR Médecine, Pôle de Formation Et de Recherche en Santé, CHU de Caen Normandie, Normandie Univ, UNICAEN, 2 rue des Rochambelles, 14000, CAEN cedex, France

    Benjamin Menahem & Arnaud Alves

  4. Departement d’Hépato-Gastroentérologie Et Nutrition, CHU de Caen Normandie, Normandie Univ, UNICAEN, 14000, CAEN, France

    Benoît Dupont

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  1. Andrea Mulliri
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  3. Arnaud Alves
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Contributions

Study concept and design: all authors. Literature screening and data acquisition: Andrea Mulliri and Benoît Dupont. First draft of manuscript: Benoît Dupont. Figure design: Benjamin Menahem. Data interpretation, critical revision of the manuscript and approval of final version: all authors.

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Correspondence to Benoît Dupont.

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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 57, 529–539 (2022). https://doi.org/10.1007/s00535-022-01886-4

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  • DOI: https://doi.org/10.1007/s00535-022-01886-4

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