Ischemic-type biliary lesions after liver transplantation: a retrospective analysis of risk factors and outcome.

BACKGROUND: Ischemic-type biliary lesions (ITBL) are the most troublesome complications after liver transplantation. Their cause remains unknown and, although some risk factors have been identified, results from different research groups are often conflicting. The goal of this study was to investigate potential risk factors for ITBL. METHODS: 565 transplantations performed between September 1997 and August 2010 were identified and divided into two cohorts: 77 in which the patient developed ITBL and 488 in which no ITBL occurred. The following factors were analyzed: donor age, patient Child-Pugh score, cold ischemia time, total ischemia time, type of perfusion solution, shipped versus non-shipped organ, ABO-compatibility versus identity between donor and recipient, Rhesus-difference versus identity between donor and recipient, presence versus absence of HLA antibodies in the patient at the time of registration on the transplant waiting list, presence in the donor of at least one HLA-C group 1 allele versus at least one HLA-C group 2 allele. HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIR) that regulate the cytotoxic activity of natural killer cells. HLA-C alleles can be allocated into two groups, HLA-C1 and HLA-C2, based on their KIR specificity. RESULTS: In a multivariate logistic regression analysis the donor age and patient Child-Pugh score C were found to be independent risk factors for ITBL (p < 0.001 and 0.007, respectively). However, the multivariate Cox regression analysis indicated that neither has an impact on graft survival. CONCLUSIONS: Donor age and patient Child-Pugh score predispose to ITBL, whereas other factors must intervene for their development.

Control of organ transplant-associated graft-versus-host disease by activated host lymphocyte infusions.

BACKGROUND: Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. METHODS: Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). RESULTS: Adoptive transfer of ex vivo activated alloreactive host T cells (aHLI) led to the control and complete resolution of severe GvHD without inducing allograft rejection. CONCLUSIONS: aHLI opens a novel therapeutic window to control solid-organ transplant-associated GvHD while preserving allograft integrity.