Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure

R. H. Wiesner, J. Ludwig, B. Van Hoek, R. A F Krom

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms ''acute'' and ''chronic'' seem inappropriate in some instances. Thus the term ''cellular rejection'' better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of ''chronic rejection,'' the term ''ductopenic rejection,'' defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss (''ductopenia''). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and γ-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation. In rare instances, the onset of ductopenic rejection can occur later than 6 mo after transplantation. Ductopenic rejection appears to be most common in patients who undergo liver transplantation for PSC; this observation has not yet been satisfactorily explained. Other risk factors predisposing the development of ductopenic rejection include a positive lymphocytotoxic crossmatch and the absence of azathioprine from the immunosuppressive regimen. Once the diagnosis of unequivocal ductopenic rejection has been confirmed histologically, the condition is frequently irreversible despite maximal immunosuppressive therapy. In these instances, retransplantation is needed as soon as hepatic synthetic function becomes severely compromised. Unfortunately, recurrence of ductopenic rejection in the transplanted graft is a common event; it has been reported in 27% to 90% of cases. The use of new immunosuppressants and new drug combinations will likely help prevent and improve treatment of the hitherto irreversible manifestations of ductopenic rejection.

Original languageEnglish (US)
Pages (from-to)721-728
Number of pages8
JournalHepatology
Volume14
Issue number4 I
DOIs
StatePublished - 1991

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Liver Failure
Bile Ducts
Allografts
Hepatocytes
Immunosuppressive Agents
Liver Transplantation
Liver
Transplantation
Arteritis
Foam Cells
Cholangitis
Cholestasis
Azathioprine
Drug Combinations
Bilirubin
Hepatitis
Alkaline Phosphatase
Therapeutics
Arteries
Transplants

ASJC Scopus subject areas

  • Hepatology

Cite this

Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. / Wiesner, R. H.; Ludwig, J.; Van Hoek, B.; Krom, R. A F.

In: Hepatology, Vol. 14, No. 4 I, 1991, p. 721-728.

Research output: Contribution to journalArticle

Wiesner, R. H. ; Ludwig, J. ; Van Hoek, B. ; Krom, R. A F. / Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. In: Hepatology. 1991 ; Vol. 14, No. 4 I. pp. 721-728.
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