Cholecystectomy and Biliary Sphincterotomy Increase Fecal Bile Loss and Improve Lipid Profile in Dyslipidemia

  • Ilia SergeevEmail author
  • Nirit Keren
  • Timna Naftali
  • Fred M. Konikoff
Original Article


Background and Aims

Bile is the only significant pathway for cholesterol elimination. Cholecystectomy (CS) increases fecal bile acid loss, and endoscopic biliary sphincterotomy (ES) is thought to have a similar effect. We speculated that a combined effect of ES + CS would further enhance fecal bile acid loss, potentially causing lipid profile changes in these patients.


Fecal bile acids and sterols were determined using gas chromatography in cohorts of post-CS + ES, post-CS and in healthy controls. The effect of ES + CS on blood lipid profile was assessed retrospectively in a single-center cohort of post-CS + ES patients, using a computerized database. Parameters of interest included demographics, medical history, and lipid profiles.


Fecal primary bile acid concentrations were increased after CS + ES compared to CS and controls (cholic acid [CA] 1.4 ng/mg vs. 0.26 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.004, chenodeoxycholic acid [CDCA] 1.92 ng/mg vs. 0.39 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.01, respectively). Fecal cholesterol excretion was similar in all three groups. Baseline serum lipid profile and subsequent changes following CS + ES were correlated. In patients with baseline hypercholesterolemia (total cholesterol (TC) > 200 mg/dl), TC levels decreased by 28.5 mg/dl, and LDL levels decreased by 21.5 mg/dl. The effect was more pronounced in those with TC > 200 mg/dl, despite of statin intake. In patients with hypertriglyceridemia [triglycerides (TG) > 200 mg/dl], TG decreased by 67.8 mg/dl following ES + CS. Among patients without dyslipidemia or dyslipidemia with adequate response to statins, the effect of ES + CS on lipid profile was minor.


Fecal bile acid loss increases following CS + ES. The effect on blood lipid profile depends on baseline TC and TG levels. Lipid profile is improved in dyslipidemic patients, while the impact of CS + ES is minimal on the normolipemic population.


Bile acids Blood lipid profile Cholecystectomy Biliary sphincterotomy 



Cholic acid


Chenodeoxycholic acid




Deoxycholic acid


Endoscopic biliary sphincterotomy


High-density cholesterol


Lithocholic acid


Total bile acids


Total blood cholesterol




Ursodeoxycholic acid



We thank Professor Uri Gophna for his help with study concept and preparation.


This study was supported in part by the Josefina Maus and Gabriela Cesarman Chair for Research in Liver Diseases, Sackler Faculty of Medicine, Tel Aviv University.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest to report.


  1. 1.
    Fort JM, Azpiroz F, Casellas F, et al. Bowel habits after cholecystectomy: physiological changes and clinical implications. Gastroenterology. 1996;111:617–622.CrossRefPubMedGoogle Scholar
  2. 2.
    Breuer NF, Jaekel S, Dommes P, et al. Fecal bile acid excretion pattern in cholecystectomized patients. Dig Dis Sci. 1986;31:953–960 CrossRefPubMedGoogle Scholar
  3. 3.
    Fromm H, Tunuguntla AK, Malavolti M, et al. Absence of significant role of bile acids in diarrhea of heterogenous group of postcholecystectomy patients. Dig Dis Sci. 1987;32:33–44. CrossRefPubMedGoogle Scholar
  4. 4.
    Sauter GH, Moussavian AC, Meyer G, et al. Bowel habits and bile acid malabsorption in the months after cholecystectomy. Am J Gastroenterol. 2002;97:1732–1735.CrossRefPubMedGoogle Scholar
  5. 5.
    Almond HR, Vlahcevic ZR, Bell CC, et al. Bile acid pools, kinetics and biliary lipid composition before and after cholecystectomy. N Engl J Med. 1973;289:1213–1216.CrossRefPubMedGoogle Scholar
  6. 6.
    Berr F, Stellaard F, Pratschke E, et al. Effects of cholecystectomy on the kinetics of primary and secondary bile acids. J Clin Investig. 1989;83:1541–1550.CrossRefPubMedGoogle Scholar
  7. 7.
    Kullak-Ublick GA, Paumgartner G, Berr F. Long term effects of cholecystectomy on bile acid metabolism. Hepatology. 1995;21:41–45.CrossRefPubMedGoogle Scholar
  8. 8.
    Malik AA, Wani ML, Tak SI, et al. Association of dyslipidemia with cholilithiasis and effect of cholecystectomy on the same. Int J Surg. 2011;9:641–642.CrossRefPubMedGoogle Scholar
  9. 9.
    Juvonen T, Kervinen K, Kairaluoma MI, et al. Effect of cholecystectomy on plasma lipid and lipoprotein levels. Hepatogastroenterology. 1995;42:377–382.PubMedGoogle Scholar
  10. 10.
    Sauerbruch T, Stellaard F, et al. Effect of endoscopic sphincterotomy on bile acid pool size and bile lipid composition in man. Digestion. 1983;27:87–92.CrossRefPubMedGoogle Scholar
  11. 11.
    Alazmi WM, Fogel EL, Watkins JL, et al. The effects of biliary sphincterotomy on serum cholesterol levels in postcholecystectomy patients: a pilot study. Can J Gastroenterol. 2005;21:81–84.CrossRefGoogle Scholar
  12. 12.
    Ung KA, Mottacki N, Rudling M, et al. Biliary sphincterotomy does not relate to diarrhea or major changes in bile acid synthesis or plasma lipids. Scand J Gastroenterol. 2009;44:1132–1138.CrossRefPubMedGoogle Scholar
  13. 13.
    Batta AK, Salen G, Arora R, et al. Side chain conjugation prevents bacterial 7-dehydroxylation of bile acids. J Biol Chem. 1990;265:10925–10928.PubMedGoogle Scholar
  14. 14.
    Keren N, Konikoff FM, Paitan Y, et al. Interactions between the intestinal microbiota and bile acids in gallstones patients. Environ Microbiol Rep. 2015;7:874–880.CrossRefPubMedGoogle Scholar
  15. 15.
    Soran H, Dent R, Dirrington P. Evidence-based goals in LDL-C reduction. Clin Res Cardiol. 2017;106:237–248.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–458.CrossRefPubMedGoogle Scholar
  17. 17.
    Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovasculardisease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996;3:213–219.CrossRefPubMedGoogle Scholar
  18. 18.
    Catapano AL, Graham I, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Denke MA, Frantz ID. Response to a cholesterol lowering diet: efficacy is greater in hypercholesterolemia subjects even after adjustment for regression to mean. Am J Med. 1993;94:626–631.CrossRefPubMedGoogle Scholar
  20. 20.
    Clifton PM, Kestin M, Abbey M, et al. Relationship between sensitivity to dietary fat and dietary cholesterol. Arterioscler Thromb Vasc Biol. 1990;10:394–401.Google Scholar
  21. 21.
    Goldberg RB, Guyon JR, Mazone T, et al. Relationships between metabolic syndrome and other baseline factors and the efficacy of ezetimibe/simvastatin and atorvastatin in patients with type 2 diabetes and hypercholesterolemia. Diabetes Care. 2010;33:1021–1024.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Smiderle L, Lima LO, Hutz MH, et al. Evaluation of sexual dimorphism in the efficacy and safety of imvastatin/atorvastatin therapy in a southern Brazilian cohort. Arq Bras Cardiol. 2014;103:33–40.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Farnier M, Salko T, Isaacson JL, et al. Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate or gemfibrozil). Am J Cardiol. 2003;92:794–797.CrossRefPubMedGoogle Scholar
  24. 24.
    Chen MM, Hale C, Stanislaus S, et al. FGF21 acts as a negative regulator of bile acid synthesis. J Endocrinol. 2018;237:139–152.CrossRefPubMedGoogle Scholar
  25. 25.
    Inagaki T, Choi M, Moschetta A, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217–225.CrossRefPubMedGoogle Scholar
  26. 26.
    Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013;3:1191–1212.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Guo S, Li L, Yin H. Cholesterol homeostasis and liver X receptor (LXR) in atherosclerosis. Cardiovasc Hematol Disord Drug Targets. 2018;18:27–33.CrossRefPubMedGoogle Scholar
  28. 28.
    Goodwin B, Watson MA, Kim H, et al. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol. 2003;17:386–394.CrossRefPubMedGoogle Scholar
  29. 29.
    Lee SD, Tontonoz P. Liver X receptors at the intersection of lipid metabolism and atherogenesis. Atherosclerosis.. 2015;242:29–36.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Dergunov AD. Apolipoprotein E genotype as a most significant predictor of lipid response at lipid-lowering therapy: mechanistic and clinical studies. Biomed Pharmacother. 2011;65:597–603.CrossRefPubMedGoogle Scholar
  31. 31.
    Brisson D, Ledoux K, Bosse Y, et al. Effect of apolipoprotein E, peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients. Pharmacogenetics. 2002;12:313–320.CrossRefPubMedGoogle Scholar
  32. 32.
    Kriaa A, Bourgin M, Potiron A, et al. Microbial impact on cholesterol and bile acid metabolism: current status and future prospects. J Lipid Res. 2019;60:323–332.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gastroenterology and HepatologyMeir Medical CenterKfar SabaIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations