Increased bile duct complications and/or chronic rejection in crossmatch positive human liver allografts

Abstract

Bile duct complications continue to be a significant cause of bile morbidity after orthotopic liver transplantation, with an incidence of 7% to 34% of patients. 1,2 Bile of duct obstruction, usually due to strictures, biliary leakage, and/or cholangitis, accounts for the majority of these complications. In contrast, although low incidence of chronic rejection has been reported under FK 506-based immunosuppression in early trials of liver transplantation, 3 chronic rejection after liver transplantation occurs in only 5% to 9% of cases, and it remains one of the most common causes of graft loss. 4,5 There have been many conflicting recent reports concerning a relationship between the bile duct-related complications or ductopenic chronic rejection and a positive crossmatch. [6][7][8] . We investigated the outcome of liver grafts from positive crossmatch donors, focusing on biliary complications and ductopenic chronic rejection, and we compared the results to a consecutive negative cross-match control group at the same time. CASE MATERIALSWe analyzed 306 consecutive adults (more than 16 years of age) primary liver transplant cases performed at Presbyterian University Hospital in Pittsburgh between November 13, 1989, and September 26, 1990. Twenty-eight (9.1%) patients were from a donor whose crossmatch test results were positive (more than 50% of donor lymphocytes were killed by dithiothreitolpretreated recipient serum). Selection of the contemporaneous 278 consecutive control patients whose crossmatch test results were negative when less than 10% of donor lymphocytes were killed, and were doubtfully or weakly positive when 11 % to 49% of donor lymphocytes were killed. None of the 306 patients received ABO blood group-incompatible grafts. All donor livers were preserved by University of Wisconsin solution.The study groups differed in crossmatch status, negative control (group 1, n = 278) and positive group (group 2, n = 28). There was a generally high degree of illness in both the positive crossmatch group and their controls, as defined by the United Network for Organ Sharing (UNOS) stratification (Table 1). The Crossmatch TestEach recipient's serum was drawn immediately before and after liver transplantation and tested for cytotoxic cross-matching activity before and after treatment with dithiothreitol (DTT), which inactivates IgM antibodies. 9 Donor T lymphocytes isolated from lymph nodes using CD3-conjugated dynabeads (Dynal, Great Neck. NY) were used.

Antibody-mediated rejection in liver transplantation: Current controversies and future directions

“…The first potential correlation between a positive T cell cross-match and graft injury was reported in 1999. 14 In this retrospective analysis, the incidence of biliary complications during the average follow-up of 7 years was found to be 36.8% for cross-match-positive recipients and 10.2% for cross-match-negative recipients. According to a more recent analysis of a single-center experience, 21 circulating DSAs were documented in 7 of 10 liver transplant recipients with biopsy-proven ductopenia.…”

Current views on rejection pathology in liver transplantation

“…7b) [94] and independent of ACR [87] where it mimics biliary obstruction with portal oedema and a ductular reaction [87]. C4d staining has been demonstrated in CR [30], a high incidence of anti-tissue antibodies has been found in patients experiencing CR [32,69] and there is an increased incidence of CR in patients with preformed DSAs [99], all of which suggest that AMR plays a role in the development of CR.…”

Implications of a positive crossmatch in liver transplantation: A 20-year review

“…With respect to graft complications, the Mayo group in 1988 observed a greater frequency of vanishing bile duct syndrome in positive crossmatch recipients 13. Approximately a decade ago, the Pittsburgh group reported an increased incidence of biliary complications and chronic rejection in recipients with a positive T cell crossmatch 14. Finally, in a recent report by Opelz et al,15 a positive T cell crossmatch in primary LT recipients was found to be significantly associated with impaired graft survival.…”