PTH-136 Activation of the pregnane X receptor (PXR) reduces the risk of early allograft dysfunction following liver transplantation. (22nd June 2015)

• Record Type: Journal Article
• Authors: Amer, A; Vallance, A; Wright, M; White, S
• Is Part Of: Gut. Volume 64(2015)Supplement 1
• Page Start: A468
• Page End: A468
• Publication Date: 2015-06-22
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2015-309861.1024
• Languages: English
• ISSNs: 0017-5749

Abstract

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.