The association of pregnane X receptor activation with outcomes after liver transplantation-A retrospective study.

ABSTRACT

BACKGROUND: Many complications following liver transplantation are linked to ischemia-reperfusion injury. Activation of the pregnane X receptor (PXR) has been shown to alleviate this process in animal models. The aim of this retrospective study was to investigate the effect of early activation of human PXR (hPXR) on postoperative complications and survival following liver transplantation. METHODS: The study included deceased donor liver transplants at a single center over 6 years. Estimated hPXR activation value on day 7 (EPAV7 ) was calculated per patient based on potency/total dose of known hPXR-activating drugs administered in the first week post-transplantation. Patients were divided into low and high hPXR activation groups based on EPAV7 . RESULTS: Overall, 240 liver transplants were included. Average EPAV7 was significantly lower in patients who developed anastomotic biliary strictures (17.7 ± 5.5 vs 35.1 ± 5.7 in stricture-free patients; P = .03) and sepsis (16.4 ± 7.1 vs 34.9 ± 5.5; P = .04). Patient survival was significantly improved in the high hPXR group (5-year survival 88.7% ± 3.8% versus 70.7% ± 5.8% [low hPXR]; P = .023). Regression analysis identified EPAV7 as a significant independent predictor of patient survival. CONCLUSION: hPXR activation within the first week of liver transplantation is a prognostic indicator of patient survival, possibly due to the associated lower biliary stricture and infection rates.