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A longitudinal study of histologic and immunohistologic changes in an experimental model of sclerosing cholangitis*

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Summary

A longitudinal study of intra and extrahepatic bile duct injuries was performed in an animal model of secondary sclerosing cholangitis induced by formalin injection into the common bile duct. Lymphocytic infiltration inside and around the bile ducts occurred seven days after injection. The disease later evolved to a fibrous cholangitis of the small bile ducts. Septal intrahepatic and extrahepatic bile duct involvement became evident three months after formalin injection. The ductular proliferation led to a progressive biliary cirrhosis with portal to portal fibrous septa. After formalin injection, bile duct cells expressed the Ia antigen in the cytoplasm and/or on the membrane of bile duct cells. The intensity of staining did not correlate with the duration or severity of the disease. Lymphocytes infiltrating into and around the bile duct were mainly T-cells. This study suggests that a local cell-mediated immune response to the injection of a toxic agent induces pathological features similar to those of sclerosing cholangitis in man.

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References

  • Ballardini G, Mirakian R, Bianchi FB, Pisi E, Doniach D, Bottazo GF (1987) Aberrant expression of HLA-DR antigens on bile duct epithelium in primary biliary cirrhosis. Relevance to pathogenesis. Lancet II:1009–1012

    Google Scholar 

  • Barbatis C, Grases P, Shepherd HA, Chapman RW, Trowell J, Jewell DPJ, McGee JO (1985) Histological features of sclerosing cholangitis in patients with chronic ulcerative colitis. J Clin Pathol 38:778–783

    Google Scholar 

  • Blackstone MO, Nemchausky BA (1978) Cholangiographic abnormalities in ulcerative colitis associated pericholangitis which resemble sclerosing cholangitis. Am J Dig Dis 23:579–585

    Google Scholar 

  • Bodenheimer HC, LaRusso NF, Thayer WR, Charland C, Staples C, Ludwig J (1983) Elevated circulating immune complexes in primary sclerosing cholangitis. Hepatology 3:150–154

    Google Scholar 

  • Bottazo F, Dean BM, McNally JM, McKay EH, Swifft PGF, Gamble DR (1985) In situ characterization of auto-immune phenomena and expression of HLA molecules in the pancreas in diabetes insulitis. N Eng J Med 313:353–360

    Google Scholar 

  • Cerf-Bensussan N, Guaroni A, Kurnick J, Bann A (1985) Intra-epithelial lymphocytes module Ia expression by intestinal epithelial cells. J Immunol 132:2244–2251

    Google Scholar 

  • Chapman WG, Marborgh BA, Rhodes J, Summerfield JA, Dick R, Scheuer PJ, Sherlock S (1980) Primary sclerosing cholangitis: a review of its clinical features, cholangiography and hepatic histology. Gut 21:870–877

    Google Scholar 

  • Chapman RW (1985) Primary sclerosing cholangitis. J Hepatol 1:179–186

    Google Scholar 

  • Chapman RW, Kelly PMA, Heryet A, Jewell DP, Fleming KA (1988) Expression of HLA-DR antigens on bile duct epithelium in primary sclerosing cholangitis. Gut 29:422–427

    Google Scholar 

  • Hanafusa T, Pujol-Barrel R, Chiovato R, Russel RCG, Domiach D, Bottazo GF (1983) Aberrant expression of HLA-DR antigen on thyrocytes in Graves disease: relevance for auto-immunity. Lancet II:1111–1115

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) Use of Avidin-Biotin-Peroxiase complex (ABC) in immuno-peroxidase techniques. A comparison between ABC and unlabelled antibody (PAP) procedure. J Histochem Cytochem 59:577–580

    Google Scholar 

  • Review by an international group (1983) Histopathology of the intrahepatic biliary tree. Liver 3:161–175

    Google Scholar 

  • Kemeny MM, Battinflora H, Blayney DW (1985) Sclerosing cholangitis after continuous hepatic artery infusion of FUDR. Ann Surg 202:240–252

    Google Scholar 

  • Larusso NF, Wiesner RH, Ludwig J, McCarty RL (1984) Primary sclerosing cholangitis. N Eng J Med 310:899–903

    Google Scholar 

  • Lindor KD, Wiesner RH, LaRusso NF, Homburger HA (1987) Enhanced autoreactivity of T-lymphocytes in primary sclerosing cholangitis. Hepatology 7:884–888

    Google Scholar 

  • Ludwig J, Barham S, Larusso N, Elveback L, Wiesner R, Mac Call J (1981) Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology 6:632–640

    Google Scholar 

  • Ludwig J, Czaja A, Dickson E, Larusso N, Wiesner R (1984) Manifestations of non suppurative cholangitis in chronic hepatobiliary diseases: morphologic spectrum, clinical correlations and terminology. Liver 4:105–116

    Google Scholar 

  • Ludwig J, Mac Carty R, Larusso N, Krom R, Wiesner R (1986) Intrahepatic cholangiectases and large-duct obliteration in primary sclerosing cholangitis. Hepatology 6:560–568

    Google Scholar 

  • McFarlane IG, Wojcicka BM, Tsantoulas DC, Portmann BC, Eddlestone AL, Williams R (1979) Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other chronic liver diseases. Gastroenterology 76:1333–1340

    Google Scholar 

  • Marymont JV, Dakhil SR, Travers H, Housholer DF (1985) Chemical cholecystitis associated with hepatic arterial chemotherapy delivered by a permanently implanted pump. Hum Pathol 16:986–990

    Google Scholar 

  • Mistilis SP (1965) Pericholangitis and ulcerative colitis. I. Pathology, etiology and pathogenesis. Ann Intern Med 63:1–16

    Google Scholar 

  • Nakanuma Y, Hirai N, Kono N, Ohta G (1986) Histological and ultrastructural examination of the intrahepatic biliary tree in primary sclerosing cholangitis. Liver 6:317–325

    Google Scholar 

  • Shea WJ, Demas BE, Goldberg HI, Hohn DC, Ferrel LD, Kerlan RK (1986) Sclerosing cholangitis associated with hepatic arterial FUDR chemotherapy: radiographic-histologig correlation. AJR 146:717–721

    Google Scholar 

  • Van Den Oord JJ, Sciot R, Desmet VJ (1986) Expression of MHC products by normal and abnormal bile duct epithelium. J Hepatol 3:310–317

    Google Scholar 

  • Wee A, Ludwig J (1985) Pericholangitis in chronic ulcerative colitis: Primary sclerosing cholangitis of the small bile ducts? Ann Intern Med 102:580–587

    Google Scholar 

  • Whiteside TL, Lasky S, Si L, Vanthiel DL (1985) Immunologic analysis of mopnonuclear cells in liver tissues and blood of patients with primary sclerosing cholangitis. Hepatology 5:468–474

    Google Scholar 

  • Wiesner RH, Larusso NF (1980) Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 79:200–206

    Google Scholar 

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This study was supported in part by a grant from the Research Council of the Faculté de Médecine, Université de Paris-Sud, and the Faculté de Médecine, Paris VI

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Bedossa, P., Houry, S., Bacci, J. et al. A longitudinal study of histologic and immunohistologic changes in an experimental model of sclerosing cholangitis*. Vichows Archiv A Pathol Anat 414, 165–171 (1989). https://doi.org/10.1007/BF00718596

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  • DOI: https://doi.org/10.1007/BF00718596

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