Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Hepatic ductopenia and vanishing bile duct syndrome

Nancy Reau, MD
Section Editor
Sanjiv Chopra, MD, MACP
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF


Vanishing bile duct syndrome refers to a group of acquired disorders resulting in progressive destruction and disappearance of the intrahepatic bile ducts and, ultimately, cholestasis. Ductopenia (a pathologic description) refers to the associated reduction in the number of intrahepatic bile ducts, a process that ultimately leads to cholestasis.

The diagnosis is made pathologically, although it can be suggested on imaging tests such as endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography when disease is advanced. There are multiple etiologies that can result in this final common pathologic picture, including autoimmune disorders, medications, genetic abnormalities, infectious diseases, and neoplastic disorders. The prognosis and treatment depend on the etiology and degree of injury. This topic will review the anatomy, classification, pathophysiology, diagnosis, and treatment of this heterogeneous group of disorders.


The biliary tree is the tubular system of ducts that transports bile from the liver to the small intestine. It is divided into intra- and extrahepatic systems. Few disease states involve both systems, thus allowing for a natural taxonomic separation between the intra- and extrahepatic biliary tree [1].

The extrahepatic system includes the right and left hepatic ducts, cystic duct, and common bile duct.

The intrahepatic biliary tree contains ducts proximal to the right and left hepatic ducts [2]. The intrahepatic system is further divided into intrahepatic large bile ducts (segmental and area ducts) that are grossly visible, and the intrahepatic small bile ducts (septal, interlobular, ductules, and canal of Hering).


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Mar 7, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Geubel AP, Sempoux CL. Drug and toxin-induced bile duct disorders. J Gastroenterol Hepatol 2000; 15:1232.
  2. Nakanuma Y, Tsuneyama K, Harada K. Pathology and pathogenesis of intrahepatic bile duct loss. J Hepatobiliary Pancreat Surg 2001; 8:303.
  3. Moore KL. The Digestive System. In: The developing Human, clinically oriented embryology, 4th ed, WB Saunders, Philadelphia 1988.
  4. Clotman F, Libbrecht L, Gresh L, et al. Hepatic artery malformations associated with a primary defect in intrahepatic bile duct development. J Hepatol 2003; 39:686.
  5. Ludwig J, Wiesner RH, LaRusso NF. Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis. J Hepatol 1988; 7:193.
  6. Desmet VJ. Vanishing bile duct syndrome in drug-induced liver disease. J Hepatol 1997; 26 Suppl 1:31.
  7. Woolf GM, Vierling JM. Disappearing intrahepatic bile ducts: the syndromes and their mechanisms. Semin Liver Dis 1993; 13:261.
  8. Ludwig J. Idiopathic adulthood ductopenia: an update. Mayo Clin Proc 1998; 73:285.
  9. Burak KW, Pearson DC, Swain MG, et al. Familial idiopathic adulthood ductopenia: a report of five cases in three generations. J Hepatol 2000; 32:159.
  10. Hubscher SG, Lumley MA, Elias E. Vanishing bile duct syndrome: a possible mechanism for intrahepatic cholestasis in Hodgkin's lymphoma. Hepatology 1993; 17:70.
  11. DeBenedet AT, Berg CL, Enfield KB, et al. A case of vanishing bile duct syndrome and IBD secondary to Hodgkin's lymphoma. Nat Clin Pract Gastroenterol Hepatol 2008; 5:49.
  12. Liangpunsakul S, Kwo P, Koukoulis GK. Hodgkin's disease presenting as cholestatic hepatitis with prominent ductal injury. Eur J Gastroenterol Hepatol 2002; 14:323.
  13. Ozkan A, Yoruk A, Celkan T, et al. The vanishing bile duct syndrome in a child with Hodgkin disease. Med Pediatr Oncol 2001; 36:398.
  14. Dich NH, Goodman ZD, Klein MA. Hepatic involvement in Hodgkin's disease. Clues to histologic diagnosis. Cancer 1989; 64:2121.
  15. Thompson HH, Pitt HA, Lewin KJ, Longmire WP Jr. Sclerosing cholangitis and histiocytosis X. Gut 1984; 25:526.
  16. Sherlock S. The syndrome of disappearing intrahepatic bile ducts. Lancet 1987; 2:493.
  17. Bihl F, Emmenegger U, Reichen J, et al. Macrophage activating syndrome is associated with lobular hepatitis and severe bile duct injury with cholestasis. J Hepatol 2006; 44:1208.
  18. Li H, Li X, Liao XX, et al. Drug associated vanishing bile duct syndrome combined with hemophagocytic lymphohistiocytosis. World J Gastrointest Endosc 2012; 4:376.
  19. Lacerda MA, Ludwig J, Dickson ER, et al. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol 1995; 90:247.
  20. Wee A, Ludwig J. Pericholangitis in chronic ulcerative colitis: primary sclerosing cholangitis of the small bile ducts? Ann Intern Med 1985; 102:581.
  21. Vierling JM, Howell CD. Disappearing bile ducts: immunologic mechanisms. Hosp Pract (Off Ed) 1990; 25:141.
  22. Murphy JR, Sjogren MH, Kikendall JW, et al. Small bile duct abnormalities in sarcoidosis. J Clin Gastroenterol 1990; 12:555.
  23. Farouj NE, Cadranel JF, Mofredj A, et al. Ductopenia related liver sarcoidosis. World J Hepatol 2011; 3:170.
  24. Burton JR Jr, Rosen HR. Diagnosis and management of allograft failure. Clin Liver Dis 2006; 10:407.
  25. Hindupur S, Yeung M, Shroff P, et al. Vanishing bile duct syndrome in a patient with advanced AIDS. HIV Med 2007; 8:70.
  26. Tyler KL, Sokol RJ, Oberhaus SM, et al. Detection of reovirus RNA in hepatobiliary tissues from patients with extrahepatic biliary atresia and choledochal cysts. Hepatology 1998; 27:1475.
  27. Lefkowitch JH, Schiff ER, Davis GL, et al. Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group. Gastroenterology 1993; 104:595.
  28. Delladetsima JK, Makris F, Psichogiou M, et al. Cholestatic syndrome with bile duct damage and loss in renal transplant recipients with HCV infection. Liver 2001; 21:81.
  29. Jung S, Lee HC, Han JM, et al. Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine. J Gastroenterol Hepatol 2002; 17:345.
  30. Kikuchi K, Miyakawa H, Abe K, et al. Vanishing bile duct syndrome associated with chronic EBV infection. Dig Dis Sci 2000; 45:160.
  31. Levy C, Lindor KD. Drug-induced cholestasis. Clin Liver Dis 2003; 7:311.
  32. Khanlou H, Sass D, Rothstein K, et al. Idiopathic adulthood ductopenia: case report and review of the literature. Arch Intern Med 2000; 160:1033.
  33. Moreno A, Carreño V, Cano A, González C. Idiopathic biliary ductopenia in adults without symptoms of liver disease. N Engl J Med 1997; 336:835.
  34. Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. J Hepatol 2001; 35:134.
  35. Smith LA, Ignacio JR, Winesett MP, et al. Vanishing bile duct syndrome: amoxicillin-clavulanic acid associated intra-hepatic cholestasis responsive to ursodeoxycholic acid. J Pediatr Gastroenterol Nutr 2005; 41:469.
  36. O'Brien CB, Shields DS, Saul SH, Reddy KR. Drug-induced vanishing bile duct syndrome: response to ursodiol. Am J Gastroenterol 1996; 91:1456.
  37. Okan G, Yaylaci S, Peker O, et al. Vanishing bile duct and Stevens-Johnson syndrome associated with ciprofloxacin treated with tacrolimus. World J Gastroenterol 2008; 14:4697.
  38. Rios R, Herrero JI, Quiroga J, et al. Idiopathic adulthood ductopenia: long-term follow-up after liver transplantation. Dig Dis Sci 2001; 46:1420.