Summary
In previous studies cytomegalovirus (CMV) infection was identified as one risk factor in the development of vanishing bile duct syndrome (VBDS) after orthotopic liver transplantation (OLT), but its precise role in relation to the pathogenesis of tissue damage is uncertain. In the present study a-interferon (α-IFN) expression in the liver was studied as an indirect marker of viral infection in serial liver biopsies from 42 patients following OLT. α-IFN was identified more frequently in the bile duct cytoplasm of patients developing VBDS, with or without evidence of preceding CMV infection (7/8 and 4/5 cases, respectively), when compared with patients with acute CMV but without evidence of VBDS (6/19 cases; P<0.05) or those with neither complication (2/10 cases; P<0.01). α-IFN was detectable in bile duct cytoplasm for a longer period in patients developing VBDS than in those with acute CMV infection alone (median 14 weeks and range 9–19, median 6 weeks and range 1–11 weeks, respectively; P< 0.025). These data indicate that persistent CMV infection of bile duct cells is a likely co-factor linked to progression to VBDS, but the processes that allow persistent viral infection and bile duct destruction remain to be determined.
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Abbreviations
- CMV:
-
Cytomegalovirus
- VBDS:
-
Vanishing bile duct syndrome
- OLT:
-
Orthotopic liver transplantation
- α-IFN:
-
α-interferon
References
Arnold JC, Gmelin K, Otto G, Alexander GJM, Williams R (1991) Effect of cytomegalovirus infection on expression of HLA-antigens in liver allografts. Transplant Proc 23:442–443
Arnold JC, Portmann BC, O'Grady JG, Naoumov NV, Alexander GJM, Williams R (1992). Persistence of cytomegalovirus genome in the liver during development of the vanishing bile duct syndrome. Hepatology 16:285–292
Foulis AK, Farquharson MA, Meager A (1987) Immunoreactive α-interferon in insulin-secreting β-cells in type 1 diabetes mellitus. Lancet 11:1423–1427
Griffiths PD, Grundy JE (1987) Molecular biology and immunology of cytomegalovirus. Biochem J 241:313–324
Khan NUD, Pulford KAF, Farquharson MA, Howatson A, Stewart C, Jackson R, McNicol AM, Foulis AV (1989). The distribution of immunoreactive interferon-alpha in normal human tissues. Immunology 66:201–206
Naoumov NV, Alexander GJM, Eddleston ALWF,Williams R (1988) In situ hybridisation in formalin fixed paraffin wax embedded liver specimens: method for detecting human and viral DNA using biotinylated probes. J Clin Pathol 41:793–798
Naoumov NV, Alexander GJM, O'Grady JG, Aldis P, Portmann BC, Williams R (1988). Rapid diagnosis of cytomegalovirus infection by in situ hybridisation in liver grafts. Lancet I:1361–1364
O'Grady JG, Alexander GJM, Sutherland S, Donaldson PT, Harvey F, Portmann BC, Calne RY, Williams R (1988). Cytomegalovirus infection and donor/recipient HLA antigens: inter-dependent co-factors in the pathogenesis of vanishing bile duct syndrome after liver transplantation. Lancet II:302–305
O'Grady JG, Williams R (1988) Liver transplantation: long-term management, complications and disease recurrence. In: Maddrey WC (ed) Liver transplantation. Elsevier, New York, pp 143–165
Oguma S, Belle S, Starzl T, Demetris AJ (1989). A histiometric analysis of chronically rejected human liver allografts: insights into the mechanism of bile duct loss: direct immunologic and ischemic factors. Hepatology 9:205–209
Portmann BC, Neuberger JM, Williams R (1983) Intrahepatic bile duct lesions. In: Calne RY (ed) Liver transplantation. Grune & Stratton, New York, pp 279–287
Scheuer PJ (1987) Acute hepatitis. In: MacSween RNM, Anthony PP, Scheuer PJ (eds) Pathology of the liver. Churchill Livingstone, London, pp 202–223
Singh N, Dummer JS, Kusne S, Breinig MK, Armstrong JA, Makowa L, Starzl TE, Ho M(1988) Infections with cytomegalovirus and other herpes viruses in 121 liver transplant recipients: transmission by donated organ and the effect of OKT 3 antibodies. J Infect Dis 158:124–131
Van Hoek B, Telenti A, Krom RAF, Wiesner RH (1990) Do intrahepatic human bile duct epithelial cells play a role in transmission of cytomegalovirusinfection? Gastroenterology [Suppl] 1277
Vierling JM, Fennel RH (1985) Histopathology of early and late human hepatic rejection: evidence of progressive destruction of interlobular bile ducts. Hepatology 5:1076–1082
Wight DGD, Portmann BC (1987) Pathology of liver transplantation, 2nd edn. Grume & Stratton, New York, pp 385–435
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Arnold, J.C., Nouri-Aria, K.T., O'Grady, J.G. et al. Hepatic α-interferon expression in cytomegalovirus-infected liver allograft recipients with and without vanishing bile duct syndrome. Clin Investig 71, 191–196 (1993). https://doi.org/10.1007/BF00180101
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DOI: https://doi.org/10.1007/BF00180101