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Histological classification of autoimmune cholestatic liver diseases

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Immunology and Liver

Part of the book series: Falk Symposium ((FASS,volume 114))

Abstract

A number of diseases may be associated with immune-mediated bile duct damage (Table 1). In practice the term autoimmunecholestatic liver disease can be applied to three main syndromes: primary biliary cirrhosis (PBC); primary sclerosing cholangitis (PSC); and overlap syndromes involving PBC, PSC and autoimmune hepatitis (AIH) in varying combinations. The use of the term autoimmunein this context is somewhat unsatisfactory, as there is no conclusive evidence to indicate that the autoantibodies which characterize these syndromes play a major pathogenetic role in mediating damage to biliary epithelial cells. Bile ducts are also targets for alloimmune damage in liver allograft rejection and graft versus host disease. Inflammatory bile duct lesions can also be seen in a number of other conditions such as sarcoidosis, hepatitis C infection and drug reactions, in which immune mechanisms may also be involved. It has also been suggested that some cases of so-called’ idiopathic’ adult ductopenia may represent examples of small duct PSC or autoimmune cholangitis in which the usual diagnostic markers are no longer present1.

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References

  1. Ludwig J. Idiopathic adulthood ductopenia: an update. Mayo Clin Proc. 1998;73:285–291.

    Article  PubMed  CAS  Google Scholar 

  2. Portmann B, MacSween RNM. Diseases of the intrahepatic bile ducts. In: MacSween RNM, Anthony PP, Scheuer PJ, Burt AD, Portmann BC, editors. Pathology of the Liver, 3rd edn. Edinburgh: Churchill Livingstone; 1994:477–512.

    Google Scholar 

  3. Van Den Oord JJV, Fevery J, de Groote J, Desmet VJ. Immunohistochemical characterization of inflammatory infiltrates in primary biliary cirrhosis. Liver. 1984;4:264–274.

    Article  PubMed  Google Scholar 

  4. Krams SM, Van de Water J, Coppel RL A et al. Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis. Hepatology. 1990;12:306–313.

    Article  PubMed  CAS  Google Scholar 

  5. Nakanuma Y. Distribution of B lymphocytes in nonsuppurative cholangitis in primary biliary cirrhosis. Hepatology. 1993;18:570–575.

    Article  PubMed  CAS  Google Scholar 

  6. Terasaki S, Nakanuma Y, Yanazaki M, Unoura M. Eosinophilic infiltration of the liver in primary biliary cirrhosis: a morphological study. Hepatology. 1993;17:206–212.

    Article  PubMed  CAS  Google Scholar 

  7. Martinez OM, Villanueva JC, Gershwin ME, Sheri MK. Cytokine patterns and cytotoxic mediators in primary biliary cirrhosis. Hepatology. 1995;21:113–119.

    PubMed  CAS  Google Scholar 

  8. Ishak KG. Sarcoidosis of the liver and bile ducts. Mayo Clin Proc. 1998;73:467–472.

    Article  PubMed  CAS  Google Scholar 

  9. Hoso M, Nakanuma Y, Kawano M et al. Granulomatous cholangitis in chronic hepatitis C: a new diagnostic problem in liver pathology. Pathol Int. 1996;46:301–305.

    Article  PubMed  CAS  Google Scholar 

  10. Chapman RW, Arborgh BMA, Rhodes JM, Summerfield J A, Dick R, Scheuer PJ. Primary sclerosing cholangitis: a review of its clinical features, cholangiography and hepatic histology. Gut. 1980;21:870–877.

    Article  PubMed  CAS  Google Scholar 

  11. Ludwig J, Colina F, Poterucha JJ. Granulomas in primary sclerosing cholangitis. Liver. 1995;15:307–312.

    PubMed  CAS  Google Scholar 

  12. Ishak KG, Zimmerman HG. Drug induced and toxic granulomatous hepatitis. Baillière’s Clin Gastroenterol. 1988;2:463–480.

    Article  CAS  Google Scholar 

  13. Ferrell LD, Lee R, Brixko C et al. Hepatic granulomas following liver transplantation. Clinicopathologic features in 42 patients. Transplantation. 1995;60:926–933.

    PubMed  CAS  Google Scholar 

  14. Kaplan KJ, Goodman ZD, Ishak KG. Liver involvement in Langerhans’ cell histiocytosis: a study of nine cases. Mod Pathol. 1999;12:370–378.

    PubMed  CAS  Google Scholar 

  15. Abt AB, Kirschner RH, Belliveau RE et al. Hepatic pathology associated with Hodgkin’s disease. Cancer. 1974;33:1564–1571.

    Article  PubMed  CAS  Google Scholar 

  16. Kadin ME, Donaldson SS, Dorfman RF. Isolated granulomas in Hodgkin’s disease. N Engl J Med. 1970;283:859–861.

    Article  PubMed  CAS  Google Scholar 

  17. Harrison RF, Hübscher SG. The spectrum of bile duct lesions in end-stage primary sclerosing cholangitis. Histopathology. 1991;19:321–327.

    Article  PubMed  CAS  Google Scholar 

  18. Wee A, Ludwig J. Pericholangitis in chronic ulcerative cholitis: primary sclerosing cholangitis of the small bile ducts? Ann Intern Med. 1985;102:581–587.

    PubMed  CAS  Google Scholar 

  19. Ludwig J. Small duct primary sclerosing cholangitis. Semin Liver Dis. 1991;11:1–17.

    Article  Google Scholar 

  20. Angulo P, Lindor KD. Primary sclerosing cholangitis. Hepatology. 1999;30:325–332.

    Article  PubMed  CAS  Google Scholar 

  21. Boberg KM, Schrumpf E, Fausa O, Elgjo K, Kolmannskog F, Haaland T et al. Hepatobiliary disease in ulcerative colitis. An analysis of 18 patients with hepatobiliary lesions classified as small-duct primary sclerosing cholangitis. Scand J Gastroenterol. 1994;29:744–752.

    Article  PubMed  CAS  Google Scholar 

  22. Ludwig J, MacCarty RL, LaRusso NF, Krom RAF, Wiesner RH. Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis. Hepatology. 1986;6:560–568.

    Article  PubMed  CAS  Google Scholar 

  23. Oguma S, Belle S, Starzl TE, Demetris AJ. A histometric analysis of chronically rejected human liver allografts: insights into mechanisms of bile duct loss: direct immunological and ischaemic factors. Hepatology. 1989;9:204–209.

    Article  PubMed  CAS  Google Scholar 

  24. Wiesner RH, Ludwig J, Van Hoek B, Krom RA. Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. Hepatology. 1991;14:721–729.

    Article  PubMed  CAS  Google Scholar 

  25. Dilawari JB, Chawala YK. Pseudosclerosing cholangitis in extrahepatic portal venous obstruction. Gut. 1992;33:272–276.

    Article  PubMed  CAS  Google Scholar 

  26. Nakanuma Y, Hoso M, Sasaki M et al. Histopathology of the liver in non-cirrhotic portal hypertension of unkown aetiology. Histopathology. 1996;28:195–204.

    Article  PubMed  CAS  Google Scholar 

  27. Woolf GM, Vierling JM. Disappearing intrahepatic bile ducts: the syndromes and their mechanisms. Semin Liver Dis. 1993;13:261–275.

    Article  PubMed  CAS  Google Scholar 

  28. Forbes A, Blanshard C, Gazzard B. Natural history of AIDS related slcerosing cholangitis: a study of 20 cases. Gut. 1993;34:116–121.

    Article  PubMed  CAS  Google Scholar 

  29. Lucas SB. Other viral and infectious diseases and HIV-related liver disease. In: MacSween RNM, Anthony PP, Scheuer PJ, Burt AD, Portmann BC, editors. Pathology of the liver. 3rd Edition Edinburgh: Churchill Livingstone; 1994: pp 269–316.

    Google Scholar 

  30. Thompson HH, Pitt HA, Lewin KJ, Longmire WP. Sclerosing cholangitis and histiocytosis X. Gut 1984; 25: 526–530.

    Article  PubMed  CAS  Google Scholar 

  31. Baron TH, Koehler RE, Rodgers WH, Fallon MB, Ferguson SM. Mast cell cholangiopathy: another cause of sclerosing cholangitis. Gastroenterology. 1995;109:1677–1681.

    Article  PubMed  CAS  Google Scholar 

  32. Terada T, Nakanuma Y. Intrahepatic cholangiographic appearance simulating primary sclerosing cholangitis in several hepatobiliary diseases. A post mortem cholangiographic and histopatho-logical study in 154 livers at autopsy. Hepatology. 1995;22:75–81.

    Article  PubMed  CAS  Google Scholar 

  33. Wiesner RH, LaRusso NF, Ludwig J, Dickson ER. Comparison of the clinicopathologic features of primary sclerosing cholangitis and primary biliary cirrhosis. Gastroenterology. 1985;88:108–114.

    PubMed  CAS  Google Scholar 

  34. Degott C, Zafrani ES, Callard P, Balkau B, Poupon RE, Poupon R. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression. Hepatology. 1999;29:1007–1012.

    Article  PubMed  CAS  Google Scholar 

  35. Nakanuma Y. Necroinflammatory changes in hepatic lobules in primary biliary cirrhosis with less well defined cholestatic changes. Human Pathology. 1993;24:378–383.

    Article  PubMed  CAS  Google Scholar 

  36. Burt AD, MacSween RNM. Bile duct proliferation-its true significance. Histopathology. 1993;23:599–602.

    Article  PubMed  CAS  Google Scholar 

  37. Desmet V, Roskams T, Van Eyken P. Ductular reaction in the liver. Pathol Res Pract. 1995;191:513–524.

    Article  PubMed  CAS  Google Scholar 

  38. Nagore N, Howe S, Boxer L, Scheuer PJ. Liver cell rosettes: structural differences in cholestasis and hepatitis. Liver. 1989;9:43–51.

    PubMed  CAS  Google Scholar 

  39. Crosby HA, Hübscher SG, Fabris L et al. Immunolocalization of putative human liver progenitor cellsin livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibodyOV-6. Am J Pathol. 1998;152:771–779.

    PubMed  CAS  Google Scholar 

  40. Roskams T, De Vos R, Van Eyken P, Myazaki H, Van Damme B, Desmet V. Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man. J Hepatol. 1998;29:455–463.

    Article  PubMed  CAS  Google Scholar 

  41. Crosby HA, Hübscher SG, Joplin RE, Kelly DA, Strain AJ. Immunolocalization of OV-6, a putative progenitor cell marker in humal fetal and diseased pediatric liver. Hepatology. 1998;28:980–985.

    Article  PubMed  CAS  Google Scholar 

  42. Rubin E, Schaffner F, Popper H. Primary biliary cirrhosis. Chronic non-suppurative destructive cholangitis. Am J Pathol. 1965;46:387–407.

    PubMed  CAS  Google Scholar 

  43. Scheuer PJ. Primary biliary cirrhosis. Proc R Soc Med. 1967;60:1257–1260.

    PubMed  CAS  Google Scholar 

  44. Popper H Schaffner F. n-suppurative destructive chronic cholangitis and chronic hepatitis. In Popper H Schaffner F editors. Progress in Liver Diseases III]. New YorkGrune & Stratton; 1970:336–3

    Google Scholar 

  45. Ludwig J, Dickson ER, McDonald GS. Staging of chronic non-suppurative cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch (A). 1978;379: 103–112.

    CAS  Google Scholar 

  46. Ludwig J. Surgical pathology of the syndrome of primary sclerosing cholangitis. Am J Surg Pathol. 1989;33:43–49.

    Google Scholar 

  47. Hübscher SG. Histological grading and staging in chronic hepatitis: clinical applications and problems.Journal of Hepatology. 1998;29:1015–1022.

    Article  PubMed  Google Scholar 

  48. Garrido MC, Hübscher SG. Accuracy of staging in primary biliary cirrhosis. J Clin Pathol. 1996;49:556–559.

    Article  PubMed  CAS  Google Scholar 

  49. Olsson R, Hagerstrand I, Broomé U et al. Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis. J Clin Pathol. 1995;48:933–935.

    Article  PubMed  CAS  Google Scholar 

  50. Horsmanns Y, Piret A, Brenard R, Rahier J, Geuvel AP. Autoimmune chronic active hepatitis responsive to immunosuppressive therapy evolving into a typical primary biliary cirrhosis syndrome: a case report. J Hepatol. 1994;21:194–198.

    Article  Google Scholar 

  51. Colombato LA, Alvarez F, Cote J, Huet PM. Autoimmune cholangiopathy: the result of consecutive primary biliary cirrhosis and autoimmune hepatitis? Gastroenterology. 1994;107:1839–1843.

    PubMed  CAS  Google Scholar 

  52. Minuk GY, Sutherland LR, Pappas SC, Kelly JK, Martin SE. Autoimmune chronic active hepatitis (lupoid hepatitis) and primary sclerosing cholangitis in two young adult females. Canad J Gastroenterol. 1988;2:22–27.

    Google Scholar 

  53. Leggett BA, Hallam A, Powell EE, Powell LW. Autoimmune chronic active hepatitis evolving to primary sclerosing cholangitis: evidence for a common pathogenesis. Hepatology. 1992;16:191A.

    Google Scholar 

  54. Lawrence SP, Sherman KE, Lawson JM, Goodman ZY. A 38 year old man with chronic hepatitis. Semin Liver Dis. 1994;14:97–105.

    Article  PubMed  CAS  Google Scholar 

  55. Brunner G, Klinge O. A cholangitis with antinuclear antibodies (immunocholangitis) resembling chronic destructive non-suppurative cholangitis. Dtsch Med Wochenschr. 1987;112:1454–1458.

    Article  PubMed  CAS  Google Scholar 

  56. Ben-Ari Z, Dhillon AP, Sherlock S. Autoimmune cholangiopathy: part of the spectrum of autoimmune chronic active hepatitis. Hepatology. 1993;18:10–15.

    Article  PubMed  CAS  Google Scholar 

  57. Chazouilleres O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998;28:296–301.

    Article  PubMed  CAS  Google Scholar 

  58. Czaja AJ. Frequency and nature of the variant syndrome of autoimmune liver disease. Hepatology. 1998;28:360–365.

    Article  PubMed  CAS  Google Scholar 

  59. Boberg KM, Fausa O, Haaland T et al Features of autoimmune hepatitis in primary sclerosing cholangitis: an evaluation of 114 primary sclerosing cholangitis patients according to a scoring system for the diagnosis of autoimmune hepatitis. Hepatology. 1996;23:1369–1376.

    Article  PubMed  CAS  Google Scholar 

  60. Lohse AW, Meyer zum Buschenfelde KH, Franz B, Kanzler S, Gerken G, Dienes HP. Characterisation of the overlap syndrome of primary biliary cirrhosis (PBC) and autoimmune hepatitis: evidence for it being a hepatitic form of PBC in genetically susceptible individuals. Hepatology. 1999;29:1078–1084.

    Article  PubMed  CAS  Google Scholar 

  61. Czaja AJ. The variant forms of autoimmune hepatitis. Ann Intern Med. 1996;125:588–598.

    PubMed  CAS  Google Scholar 

  62. Taylor SL, Dean PJ, Riely CA. Primary autoimmune cholangitis. An alternative to antimito-chondrial antibody-negative primary biliary cirrhosis. Am J Surg Pathol. 1994;18:91–99.

    Article  PubMed  CAS  Google Scholar 

  63. Goodman ZD, McNally PR, Davis Dr, Ishak KG. Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases. Dig Dis Sci. 1995;40:1232–1242.

    Article  PubMed  CAS  Google Scholar 

  64. Heathcote J. Autoimmune cholangitis. Gut. 1997;40:440–442.

    PubMed  CAS  Google Scholar 

  65. Michieletti P, Wanless IR, Katz A et al. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. Gut. 1994;35:260–265.

    Article  PubMed  CAS  Google Scholar 

  66. Sanchez-Pobre P, Castellano G, Colina F et al. Antimitochondrial antibody-negative chronic nonsuppurative destructive cholangitis. Atypical primary biliary cirrhosis or autoimmune cholangitis? J Clin Gastroenterol. 1996;23:191–198.

    Article  PubMed  CAS  Google Scholar 

  67. Kinoshita H, Omargi K, Whittingham S et al. Autoimmune cholangitis and primary biliary cirrhosis-an autoimmune enigma. Liver. 1999;19:122–128.

    Article  PubMed  CAS  Google Scholar 

  68. Lacerda MA, Ludwig J, Dickson ER, Jorgensen RA, Lindor KD. Antimitochondrial antibody-negative primary biliary cirrhosis. Am J Gastroenterol. 1995;90:247–249.

    PubMed  CAS  Google Scholar 

  69. Tsuneyama K, Van de Water J, Van Thiel D et al. Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis. Hepatology. 1995;22:1440–1446.

    PubMed  CAS  Google Scholar 

  70. Kaserer K, Exner M, Mosberger I, Penner E, Wrba F. Characterization of the inflammatory infiltrate in autoimmune cholangitis. A morphological and immunohistochemical study. Virchows Archiv. 1998;432:217–222.

    Article  PubMed  CAS  Google Scholar 

  71. Heathcote EJ. Autoimmune cholangitis. In: Lindor KD, Dickson ER, editors. Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis and Adult Cholangiopathies. Philadelphia: WB Saunders; 1998:303–311.

    Google Scholar 

  72. Vierling JM. Autoimmune cholangiopathy. Clin Liver Dis. 1999;3:571–584.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. S. G. Hübscher
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Editors and Affiliations

  1. Abt. Gastroenterologie/Hepatologie Zentrum Innere Medizin, Medizinische Hochscule Hannover, Carl-Neuberg Str. 1, D-30625, Hannover, Germany

    M. P. Manns

  2. Medizinische Klinik II, Klinikum Grosshadern der LMU München, Marchioninistr. 15, D-81377, München, Germany

    G. Paumgartner

  3. Abt. Gastroenterologie Zentrum der Innere Medizin, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60596, Frankfurt, Germany

    U. Leuschner

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Hübscher, S.G. (2000). Histological classification of autoimmune cholestatic liver diseases. In: Manns, M.P., Paumgartner, G., Leuschner, U. (eds) Immunology and Liver. Falk Symposium, vol 114. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4000-3_20

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  • DOI: https://doi.org/10.1007/978-94-011-4000-3_20

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5768-4

  • Online ISBN: 978-94-011-4000-3

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