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PTH-136 Activation of the pregnane X receptor (PXR) reduces the risk of early allograft dysfunction following liver transplantation
  1. A Amer1,2,
  2. A Vallance2,
  3. M Wright2,
  4. S White1
  1. 1Institute of Transplantation, Freeman Hospital
  2. 2Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK

Abstract

Introduction There has been increasing interest in the pregnane X receptor (PXR) in recent years as a promising drug target for the treatment of inflammatory liver disease. Our group has previously demonstrated that activation of the PXR reduces oxidative stress and fibrosis in a rat model of liver ischaemia-reperfusion injury. The aim of this study was to investigate the effect of PXR activation on early graft function in clinical liver transplantation.

Method Data was collected retrospectively for all patients receiving liver transplants in a major transplant centre in the UK over the past three years. Patients were divided into high and low PXR activation groups based on the potency and number of PXR-activating drugs administered over the first week of transplantation. Early allograft dysfunction (EAD) was measured using a validated scoring system and was compared between the two groups in addition to graft and patient survival.

Results Eighty three patients were considered eligible for inclusion in this study (n = 43 and 40 in the low and high PXR activation groups respectively). The incidence of EAD was significantly higher in the low PXR activation group (30.2% vs. 10% in the high PXR activation group; P < 0.05). No significant differences in graft or patient survival were demonstrated in this small cohort.

Conclusion Activation of the PXR resulted in a reduction in EAD following liver transplantation in the clinical setting; consistent with our previous results in the animal model. Our findings have important implications for the potential reduction of graft loss following DCD liver transplantation.

Disclosure of interest None Declared.

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