Late biliary strictures following liver transplantation are a major source of graft loss, and usually attributed to vascular problems. In many cases, however, vascular pathologies are missing. This study investigates the association of late biliary strictures and the presence of pre-transplant donor specific antibodies (DSA) and positive cross match.

29 cases of late extra-hepatic biliary strictures, occurring 6 weeks to 3 years after transplantation, were identified by MRCP, ERCP or PTC in recipients of deceased donor liver transplants between 2002 and 2011 (n=286). Their preoperative sera were retrospectively examined for DSA using Luminex single bead assays. Donor cells were cross-matched using flow cytometry. 20 recipients with no evidence of biliary pathologies served as control. Acute rejection, hepatitis and demographic criteria were considered for matching the control group.

Cumulative class II MFI >500 and/or B-cell cross-match positivity was found to be strongly associated with the incidence of late extra-hepatic biliary strictures. Class I DSA did not reveal any association. The study group showed cumulative class II DSA >500 MFI in 24/29 patients (83%) and B-cell crossmatch positivity in 20/29 patients (69%). Using both criteria, 26/29 recipients (90%) could have been identified prior to transplantation for being at risk to develop late biliary strictures. Only 3/20 recipients (15%) of the control group showed B-cell cross-match positivity. None of them had a cumulative class II MFI >200. None of 4/20 controls (20%) with cumulative class II MFI >500 showed a positive B-cell cross-match.

This is the first evidence indicating that pre-transplant class II DSA and B-cell cross-match positivity are strongly associated with the risk of developing late extra-hepatic biliary strictures following liver transplantation. These data are suggestive for an immunological aetiology of non-vascular late biliary strictures.

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