The association of pregnane X receptor activation with outcomes after liver transplantation-A retrospective study.
Female
Follow-Up Studies
Graft Rejection
/ diagnosis
Graft Survival
Humans
Liver Transplantation
/ adverse effects
Living Donors
/ supply & distribution
Male
Middle Aged
Postoperative Complications
/ diagnosis
Pregnane X Receptor
/ metabolism
Prognosis
Retrospective Studies
Risk Factors
Survival Rate
biliary strictures
liver transplantation
pregnane X receptor
Journal
Clinical transplantation
ISSN: 1399-0012
Titre abrégé: Clin Transplant
Pays: Denmark
ID NLM: 8710240
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
11
07
2019
revised:
30
09
2019
accepted:
06
10
2019
pubmed:
20
10
2019
medline:
24
10
2020
entrez:
20
10
2019
Statut:
ppublish
Résumé
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. The study included deceased donor liver transplants at a single center over 6 years. Estimated hPXR activation value on day 7 (EPAV Overall, 240 liver transplants were included. Average EPAV 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.
Sections du résumé
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 (EPAV
RESULTS
Overall, 240 liver transplants were included. Average EPAV
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.
Substances chimiques
NR1I2 protein, human
0
Pregnane X Receptor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13734Subventions
Organisme : Medical Research Council
ID : MC_PC_13071
Pays : United Kingdom
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Kliewer SA, Moore JT, Wade L, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92(1):73-82.
Zhang X, gao Y, wang Y, et al. Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor. Drug Des Devel Ther. 2015;9:6343-6362.
Hu D, Wang Y, Chen Z, et al. The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation. J Ethnopharmacol. 2015;169:109-123.
Zhang J, Ding L, Wang B, et al. Notoginsenoside R1 attenuates experimental inflammatory bowel disease via pregnane X receptor activation. J Pharmacol Exp Ther. 2015;352(2):315-324.
Hu D, Wang Y, Chen Z, et al. Artemisinin protects against dextran sulfate-sodium-induced inflammatory bowel disease, which is associated with activation of the pregnane X receptor. Eur J Pharmacol. 2014;738:273-284.
Shah YM, Ma X, Morimura K, Kim I, Gonzalez FJ. Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappaB target gene expression. Am J Physiol Gastrointest Liver Physiol. 2007;292(4):G1114-1122.
Cheng J, Shah YM, Ma X, et al. Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther. 2010;335(1):32-41.
Mencarelli A, D'Amore C, Renga B, et al. Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune dysfunction in a mouse model of arthritis. Mar Drugs. 2013;12(1):36-53.
Marek CJ, Tucker SJ, Konstantinou DK, et al. Pregnenolone-16alpha-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms. Biochem J. 2005;387(Pt 3):601-608.
Wallace K, Cowie DE, Konstantinou DK, et al. The PXR is a drug target for chronic inflammatory liver disease. J Steroid Biochem Mol Biol. 2010;120(2-3):137-148.
Amer AO, Probert PM, Dunn M, et al. Sustained isoprostane E2 elevation, inflammation and fibrosis after acute ischaemia-reperfusion injury are reduced by pregnane X receptor activation. PLoS ONE. 2015;10(8):e0136173.
Ayoub WS, Esquivel CO, Martin P. Biliary complications following liver transplantation. Dig Dis Sci. 2010;55(6):1540-1546.
Op den Dries S, Sutton ME, Lisman T, Porte RJ. Protection of bile ducts in liver transplantation: looking beyond ischemia. Transplantation. 2011;92(4):373-379.
Joint Formulary Committee. British national formulary. 69th ed. London: British Medical Association: Pharmaceutical Society of Great Britain; 2015.
Shukla SJ, Sakamuru S, Huang R, et al. Identification of clinically used drugs that activate pregnane X receptors. Drug Metab Dispos. 2011;39(1):151-159.
Burton ME. Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring. 4th ed. Baltimore: Lippincott Williams & Wilkins; 2006.
Shukla SJ, Nguyen DT, Macarthur R, et al. Identification of pregnane X receptor ligands using time-resolved fluorescence resonance energy transfer and quantitative high-throughput screening. Assay Drug Dev Technol. 2009;7(2):143-169.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-213.
Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010;16(8):943-949.
Sarkar M, Watt KD, Terrault N, Berenguer M. Outcomes in liver transplantation: does sex matter? J Hepatol. 2015;62(4):946-955.
Jay C, Ladner D, Wang E, et al. A comprehensive risk assessment of mortality following donation after cardiac death liver transplant - an analysis of the national registry. J Hepatol. 2011;55(4):808-813.
Mourad MM, Algarni A, Liossis C, Bramhall SR. Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation. World J Gastroenterol. 2014;20(20):6159-6169.
Ryu CH, Lee SK. Biliary strictures after liver transplantation. Gut Liv. 2011;5(2):133-142.
Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87.
Fagerholm U. Prediction of human pharmacokinetics-evaluation of methods for prediction of volume of distribution. J Pharm Pharmacol. 2007;59(9):1181-1190.