Liver injury possibly related to drug interaction after liver transplant: a case report

Zhu, Liqin; Jiang, Wentao; Pan, Cheng; Liu, Y. H.; Thian, Yee Liang

doi:10.1111/jcpt.12150

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…This remains an intimidating dilemma owing to the known hepatotoxicity of fluoropyrimidines. There are case reports of both liver injury and graft rejection in liver transplant recipients receiving fluoropyrimidine-based chemotherapy [124,125]. These findings explain the caution with which the treating oncologists approached the care for this patient.…”

Section: Discussionmentioning

confidence: 98%

DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report

et al. 2019

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5-Fluorouracil remains a foundational component of chemotherapy for solid tumour malignancies. While considered a generally safe and effective chemotherapeutic, 5-fluorouracil has demonstrated severe adverse event rates of up to 30%. Understanding the pharmacokinetics of 5-fluorouracil can improve the precision medicine approaches to this therapy. A single enzyme, dihydropyrimidine dehydrogenase (DPD), mediates 80% of 5-fluorouracil elimination, through hepatic metabolism. Importantly, it has been known for over 30-years that adverse events during 5-fluorouracil therapy are linked to high systemic exposure, and to those patients who exhibit DPD deficiency. To date, pre-treatment screening for DPD deficiency in patients with planned 5-fluorouracil-based therapy is not a standard of care. Here we provide a focused review of 5-fluorouracil metabolism, and the efforts to improve predictive dosing through screening for DPD deficiency. We also outline the history of key discoveries relating to DPD deficiency and include relevant information on the potential benefit of therapeutic drug monitoring of 5-fluorouracil. Finally, we present a brief case report that highlights a limitation of pharmacogenetics, where we carried out therapeutic drug monitoring of 5-fluorouracil in an orthotopic liver transplant recipient. This case supports the development of robust multimodality precision medicine services, capable of accommodating complex clinical dilemmas.

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Section: Discussionmentioning

confidence: 98%

DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report

et al. 2019

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“…MSC's hold promise on various levels, when seeded onto a liver matrix they have been shown to differentiate into hepatocytes and when transplanted restore liver function in a lethal liver failure model [11]. Our scaffolds were seeded for 10 days with AD-MSC's and although they did not express any markers of differentiation (HNF -alpha or CK 19data not shown), probably due to the short seeding period, the cells showed changes in cellular morphology and migration indicative of a degree of cellular-matrix cross talk.…”

Section: Discussionmentioning

confidence: 99%

“…To date different approaches have been developed for creating acellular liver matrices from different species e.g. rodents [10] [11], porcine [12][13][14], sheep [15] and human [16,17] using various combinations of chemicals, enzymes and physical forces. Detergents and enzymes are known to have a negative impact on the ECM of biological tissue; this damage can be mitigated by limiting the duration and exposure [18].…”

Section: Introductionmentioning

confidence: 99%

“…Different cells types have been used for re-cellularisation of de-cellularised liver matrices, including iPSC induced hepatocytes [7], human primary hepatocytes [23] and mesenchymal stromal cells. The seeding of the latter onto a liver scaffold supported hepatic differentiation and the ability to restore liver function in a severe liver failure model [11]. As such, the use of mesenchymal stromal cells as a potential cell source may be more favourable as they do not carry the potential tumorigenic risk associated with iPSC's.…”

Section: Introductionmentioning

confidence: 99%

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Development and Characterization of a Porcine Liver Scaffold

Ansari

Southgate

Obiri-Yeboa

et al. 2020

Stem Cells and Development

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The growing number of patients requiring liver transplantation for chronic liver disease cannot be currently met due to a shortage in donor tissue. As such, alternative tissue engineering approaches combining the use of acellular biological scaffolds and different cell populations (hepatic or progenitor) are being explored to augment the demand for functional organs. Our goal was to produce a clinically relevant sized scaffold from a sustainable source within 24 hours, whilst preserving the extra cellular matrix (ECM) to facilitate cell repopulation at a later stage. Whole porcine livers underwent perfusion de-cellularisation via the hepatic artery and hepatic portal vein using a combination of saponin, sodium deoxycholate (SOC) and deionised water washes resulting in an acellular scaffold with an intact vasculature and preserved ECM. Molecular and immuno-histochemical analysis (collagen I and IV and laminin) showed complete removal of any DNA material, together with excellent retention of glycosaminoglycans and collagen. FTIR analysis showed both absence of nuclear material and removal of any detergent residue, which was successfully achieved after additional ethanol gradient washes.Samples of the de-cellularised scaffold were assessed for cytotoxicity by seeding with porcine adipose derived mesenchymal stem cells in vitro, these cells over a 10 day period showed attachment and proliferation. Perfusion of the vascular tree with contrast media followed by CT imaging showed an intact vascular network. In vivo implantation of whole intact non-seeded livers, into a porcine model (as auxiliary graft) showed uniform perfusion macroscopically and histologically. Using this method, it is possible to create an acellular, clinically sized, liver scaffold with intact vasculature in less than 24 hours.

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Capecitabine/tacrolimus/warfarin interaction

2014

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Liver injury possibly related to drug interaction after liver transplant: a case report

Abstract: Close monitoring and prompt discontinuation of the drugs with high volume of distribution and metabolized through the liver are necessary to avoid drug-drug interaction in liver transplant patients.

Cited by 3 publications

References 11 publications

DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report

DPYD and Fluorouracil-Based Chemotherapy: Mini Review and Case Report

Development and Characterization of a Porcine Liver Scaffold

Capecitabine/tacrolimus/warfarin interaction

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