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

Amer, Aimen; McColl, Kirsty; Bouayyad, Sarah; Kanwar, Aditya; Sen, Gourab; French, Jeremy; Manas, Derek; Wright, Matthew C.; White, Steve

doi:10.1111/ctr.13734

Cited by 5 publications

(5 citation statements)

References 23 publications

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“…The pathophysiology for the development of anastomotic stricture is believed to be ischemia or fibrosis of the bile duct following a suboptimal surgical technique or a bile leak in the early postoperative period [587]. Small caliber of the bile ducts, size mismatch between donor and recipient ducts, postoperative bile leak, inappropriate suture material, tension at the anastomosis, and excessive use of cauterization to control bleeding were risk factors for anastomotic strictures [587][588][589][590].…”

Section: Portal Vein and Hepatic Vein Complicationsmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation

Kim,

Yoon,

Kim

et al. 2024

Hepatol Int

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Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines. Keywords Living donor liver transplantation • Deceased donor liver transplantation • Multidisciplinary • GradeSpecial consideration: LDLT in ACLF In a study of 112 LDLT recipients with ACLF, defined by the APASL definition, post-LT outcomes were excellent (92.9% at 5 years) [69]. In a study on high-model end-stage liver disease (MELD) (score ≥ 30) LDLT recipients with ACLF (n = 190), defined by the World Congress of Gastroenterology [70], the 5-year survival rate was 72.1% [71]. In a study of 117 LDLT recipients who had ACLF, as defined by the EASL-CLIF definition, post-transplant survival after LDLT was 92.9%, 85.4%, and 75.6% at 1 year, while mortality rate without LT was 28.5%, 77.7%, and 93.4% at 90 days, for ACLF grades 1, 2, and 3, respectively [72]. These data indicate that LDLT can be a life-saving treatment option for patients with ACLF.LDLT differs significantly from DDLT, as the timing of LDLT can be determined by the transplant team. There are advantages and disadvantages of LDLT in the setting of ACLF. The benefit of LDLT in patients with ACLF is its ability to provide rapid transplantation to critically ill patients [73], without waiting for deceased donor allocation. The ideal time for LT can be selected by transplant team when willing living donor is available. If ideal time for LT can be selected in the dynamic course of ACLF, this may improve post-LT outcome. The disadvantages of LDLT include the need for healthy, willing liver donor, and the use of partial grafts for critically ill patients. A graft-to-recipient weight ratio (GRWR) is a factor associated with post-LT outcomes in LDLT [74]. The donor risk index is a factor associated with post-LT outcomes for patients with ACLF who received DDLT [66,75]. This indicates that DDLT, which uses whole liver grafts, might be a better compared to LDLT, which uses partial grafts, in ACLF. In addition, there are uncertainties regarding the criteria for living donor graft quality that is required for critically ill patients with ACLF. In studies that reported...

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Section: Portal Vein and Hepatic Vein Complicationsmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation

Kim,

Yoon,

Kim

et al. 2024

Hepatol Int

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“…Although many risk factors have been implicated in the development of AS, there is discordance among studies. Risk factors for the development of AS can be grouped into several broad categories, including ischaemic (surgical technique, longer intensive care unit (ICU) stay, and longer cold and warm ischaemia times), genetic factors, and inflammatory (CMV, Epstein-Barr Virus, and acute/chronic cellular rejection) 55 56…”

Section: Anastomotic Stricturesmentioning

confidence: 99%

Post-transplant biliary complications: advances in pathophysiology, diagnosis, and treatment

Fasullo

Patel

Khanna

et al. 2022

BMJ Open Gastroenterol

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Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease. Long-term survival is excellent, yet LT recipients are at risk of significant complications. Biliary complications are an important source of morbidity after LT, with an estimated incidence of 5%–32%. Post-LT biliary complications include strictures (anastomotic and non-anastomotic), bile leaks, stones, and sphincter of Oddi dysfunction. Prompt recognition and management is critical as these complications are associated with mortality rates up to 20% and retransplantation rates up to 13%. This review aims to summarise our current understanding of risk factors, natural history, diagnostic testing, and treatment options for post-transplant biliary complications.

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“…Specific interactions of interest include the effect of the anti-tubercular drug rifampicin on isoniazidmediated hepatotoxicity via the accumulation of the endogenous hepatotoxin protoporphyrin IX in the liver (Li, Lu et al 2013). PXR may prognosticate for survival in patients undergoing liver transplantation (Amer, McColl et al 2019), perhaps via its effects on tacrolimus metabolism (Stifft, van Kuijk et al 2018). In addition, recent work has highlighted new roles for PXR as a factor promoting radio resistance in cancer (Niu, Cui et al 2022), drug sensitivity or resistance (Creusot, Gassiot et al 2020, Sári, Mikó et al 2020, Matheux, Gassiot et al 2021, Ozawa, Miura et al 2021, and promotes striated and smooth muscle metabolism and physiology (Swales, Moore et al 2012, Ortiz-Flores, Portilla-Martínez et al 2020.…”

Section: Brief Historical Perspectivementioning

confidence: 99%

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

Dvořák

Mani

2022

Drug Metab Dispos

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Xenobiotic receptors, for example like the pregnane X receptor, regulate multiple host physiological pathways including xenobiotic metabolism, certain aspects of cellular metabolism, and innate immunity. These ligand-dependent nuclear factors regulate gene expression via genomic recognition of specific promoters and transcriptional activation of the gene. Natural or endogenous ligands are not commonly associated with this class of receptors; however, since these receptors are expressed in a cell-type specific manner in the liver and intestines, there has been significant recent effort to characterize microbially derived metabolites as ligands for these receptors. In general, these metabolites are thought to be weak micromolar affinity ligands. This journal anniversary minireview will focus on recent efforts to derive potentially non-toxic microbial metabolite chemical mimics that could one day be developed as drugs combating xenobiotic-receptor modifying pathophysiology. The review will include our perspective of the field and recommend certain directions for future research. SIGNIFICANCE STATEMENTThe xenobiotic receptors (XR) regulate host drug metabolism, cellular metabolism, and immunity. Their presence in host intestines allows them to function not only as xenosensors, but also to respond to the complex metabolic environment present in the intestines. Specifically, this review focuses on describing microbial metabolite-XR interactions and the translation of these findings towards discovery of novel chemical mimics as potential drugs of the future for diseases such as inflammatory bowel disease.

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

Cited by 5 publications

References 23 publications

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation

Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation

Post-transplant biliary complications: advances in pathophysiology, diagnosis, and treatment

Microbial Metabolites as Ligands to Xenobiotic Receptors: Chemical Mimicry as Potential Drugs of the Future

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