Common Bile Duct Ligation as Model for Secondary Biliary Cirrhosis

  • Sanne Van Campenhout
  • Hans Van Vlierberghe
  • Lindsey DevisscherEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1981)


Cholestatic liver disease covers a range of biliary disorders marked by an impaired bile duct flow. Various conditions can result in bile obstruction including choledocholithiasis, surgical trauma, and autoimmune disorders. Cholestatic liver disease can be mild but generally progresses to more severe conditions with increased hepatobiliary injury, cholangitis, and ultimately liver fibrosis and cirrhosis. An extensively used experimental model to investigate the pathophysiology of biliary cirrhosis and potential novel therapies is the common bile duct ligation in mice and rats. Common bile duct ligation induces the different stages of cholestatic-induced liver disease being cholestasis, subsequently accompanied by inflammation and finally liver fibrosis and cirrhosis. In this protocol, an outline of the surgical procedures to conduct common bile duct ligation in mice is provided. The major steps include the isolation of the common bile duct, followed by ligation and dissection.

Key words

Common bile duct ligation Cholestasis Biliary cirrhosis Liver disease Mouse surgery Portal hypertension Hepatopulmonary syndrome Obstructive jaundice Animal model Ascites 



This work was financially supported by the grants of the Special Research Funds—University Ghent (BOF-UGent) and the Fund for Scientific Research—Flanders (FWO-Vlaanderen).


  1. 1.
    Boberg KM, Cadamuro M, Fabris L et al (2017) Biliary disease. Springer International Publishing, ChamGoogle Scholar
  2. 2.
    Selvasekaran R, Nagalakshmi G, Anandan H (2017) Clinical spectrum of presentation of obstructive jaundice in inflammation, stone disease, and malignancy. Int J Sci Study 5:10–14CrossRefGoogle Scholar
  3. 3.
    Kremer AE, Rust C, Eichhorn P et al (2009) Immune-mediated liver diseases: programmed cell death ligands and circulating apoptotic markers. Expert Rev Mol Diagn 9:139–156CrossRefGoogle Scholar
  4. 4.
    Zakharia K, Tabibian A, Lindor KD et al (2018) Complications, symptoms, quality of life and pregnancy in cholestatic liver disease. Liver Int 38:399–411CrossRefGoogle Scholar
  5. 5.
    Jansen PLM, Ghallab A, Vartak N et al (2017) The ascending pathophysiology of cholestatic liver disease. Hepatology 65:722–738CrossRefGoogle Scholar
  6. 6.
    Pavlidis ET, Pavlidis TE (2018) Pathophysiological consequences of obstructive jaundice and perioperative management. Hepatob Pancreatic Dis Int 17:17–21CrossRefGoogle Scholar
  7. 7.
    Moezi L, Dehpour AR (2013) Cardiovascular abnormalities in obstructive cholestasis: the possible mechanisms. Liver Int 33:7–15CrossRefGoogle Scholar
  8. 8.
    Wu W, Zhang JL, Yang WL et al (2016) Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome. J Gastroenterol Hepatol 31:1888–1894CrossRefPubMedGoogle Scholar
  9. 9.
    Geerts AM, Vanheule E, Praet M et al (2008) Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation. Int J Exp Pathol 89:251–263CrossRefPubMedGoogle Scholar
  10. 10.
    Shikata F, Sakaue T, Nakashiro K et al (2014) Pathophysiology of lung injury induced by common bile duct ligation in mice. PLoS One 9:14CrossRefGoogle Scholar
  11. 11.
    Fallon MB, Abrams GA, McGrath JW et al (1997) Common bile duct ligation in the rat: a model of intrapulmonary vasodilatation and hepatopulmonary syndrome. Am J Physiol-Gastroint Liver Physiol 272:G779–G784CrossRefGoogle Scholar
  12. 12.
    Raevens S, Geerts A, Paridaens A et al (2018) Placental growth factor inhibition targets pulmonary angiogenesis and represents a novel therapy for hepatopulmonary syndrome in mice. Hepatology 68:634–651CrossRefGoogle Scholar
  13. 13.
    Marques TG, Chaib E, da Fonseca JH et al (2012) Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection. Acta Cir Bras 27:589–594CrossRefGoogle Scholar
  14. 14.
    Georgiev P, Jochum W, Heinrich S et al (2008) Characterization of time-related changes after experimental bile duct ligation. Br J Surg 95:646–656CrossRefGoogle Scholar
  15. 15.
    Tag CG, Sauer-Lehnen S, Weiskirchen S et al (2015) Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis. J Vis Exp:11Google Scholar
  16. 16.
    Xie CX, Ma B, Wang N et al (2017) Comparison of serological assessments in the diagnosis of liver fibrosis in bile duct ligation mice. Exp Biol Med 242:1398–1404CrossRefGoogle Scholar
  17. 17.
    Zhang CY, Yuan WG, He P et al (2016) Liver fibrosis and hepatic stellate cells: etiology, pathological hallmarks and therapeutic targets. World J Gastroenterol 22:10512–10522CrossRefPubMedGoogle Scholar
  18. 18.
    Chaniotakis I, Spyrliadis A, Katsimpoulas M et al (2016) The mouse and the rat in surgical research. The anesthetic approach. J Hell Vet Med Soc 67:147–162CrossRefGoogle Scholar
  19. 19.
    Arras M, Autenried P, Rettich A et al (2001) Optimization of intraperitoneal injection anesthesia in mice: drugs, dosages, adverse effects, and anesthesia depth. Comp Med 51:443–456Google Scholar
  20. 20.
    Hildebrandt IJ, Su H, Weber WA (2008) Anesthesia and other considerations for in vivo imaging of small animals. ILAR J 49:17–26CrossRefGoogle Scholar
  21. 21.
    Baker P, Barraclough B, Berry W et al (2009) Section II: Ten essential objectives for safe surgery: review of the evidence and recommendations. In: Gawande A, Weiser T (eds) WHO guidelines for safe surgery 2009: safe surgery saves lives. World Health Organization, Geneva, pp 43–61Google Scholar
  22. 22.
    Welberg LAM, Kinkead B, Thrivikraman KV et al (2006) Ketamine-xylazine-acepromazine anesthesia and postoperative recovery in rats. J Amer Assoc Lab Anim Sci 45:13–20Google Scholar
  23. 23.
    Martini FH, Tallitsch RB, Nath JL et al (2015) Human anatomy, 6th edn. Pearson, BostonGoogle Scholar
  24. 24.
    Yang Y, Chen B, Chen Y et al (2015) A comparison of two common bile duct ligation methods to establish hepatopulmonary syndrome animal models. Lab Anim 49:71–79CrossRefGoogle Scholar
  25. 25.
    Goodman ZD (2007) Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol 47:598–607CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Sanne Van Campenhout
    • 1
  • Hans Van Vlierberghe
    • 1
  • Lindsey Devisscher
    • 2
    Email author
  1. 1.Internal Medicine and PediatricsGhent UniversityGhentBelgium
  2. 2.Basic and Applied Medical SciencesGhent UniversityGhentBelgium

Personalised recommendations