Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients

Fairfield, Cameron J; Penninga, Luit; Powell, James J.; Harrison, Ewen M; Wigmore, Stephen J.

doi:10.1002/14651858.cd007606.pub3

Cited by 21 publications

(15 citation statements)

References 123 publications

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“…Although old studies on steroid sparing regimens (GC minimization or discontinuation after 3 mo of transplant surgery) showed higher rates of acute rejection and graft loss, in those studies immunosuppressive regimens contained cyclosporine as a CNI[ 13 ]. Nowadays, induction therapies with thymoglobulin or IL2 receptor antagonists and new maintenance immunosuppressive regimens, such as tacrolimus instead of cyclosporine as CNI or mTOR inhibitors, in combination with low doses of CNIs and/or mycophenolate, provided the opportunity for successful steroid-sparing immunosuppression regimens[ 1 , 9 - 11 , 14 , 15 ]. Although, steroid sparing immunosuppressive regimens were used for low immunological risk patients, an analysis of 169479 renal transplant patients using the Scientific Registry of Transplant Recipients found that rapid discontinuation of steroids can be used in all adult and pediatric first kidney transplant recipients from either a deceased or living donor and in second kidney transplant recipients from a living donor or patients at risk for rejection or recurrence of underlying diseases without decreasing patients’ or graft survival rates.…”

Section: Transplant Recipientsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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Section: Transplant Recipientsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

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“…The combination of drugs seems to be important however with the effects of tacrolimus on MSC being reversed by the combined use of oxytocin (118). Whilst it has been demonstrated that avoidance of corticosteroids in patients following a liver transplantation is likely to be safe and reduce associated complications (119), corticosteroids are still widely used in the setting of liver transplantation, both for induction of immunosuppression and treatment of rejection (120). When combined with dexamethasone in in vitro assays the ability of MSC to suppress T cell proliferations seems to be reversed (121), however the ability of MSC to suppress natural killer cell activation seems to be enhanced with dexamethasone augmenting the ability of MSC to IL-2 and IL-12 induced CD69 expression and reduce production of IFNγ (122).…”

Section: Msc As a Therapy In Post-transplant Carementioning

confidence: 99%

Mesenchymal Stromal Cells, a New Player in Reducing Complications From Liver Transplantation?

Owen

Newsome

2020

Front. Immunol.

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In response to the global burden of liver disease there has been a commensurate increase in the demand for liver transplantation. However, due to a paucity of donor organs many centers have moved toward the routine use of marginal allografts, which can be associated with a greater risk of complications and poorer clinical outcomes. Mesenchymal stromal cells (MSC) are a multi-potent progenitor cell population that have been utilized to modulate aberrant immune responses in acute and chronic inflammatory conditions. MSC exert an immunomodulatory effect on innate and adaptive immune systems through the release of both paracrine soluble factors and extracellular vesicles. Through these routes MSC can switch the regulatory function of the immune system through effects on macrophages and T regulatory cells enabling a switch of phenotype from injury to restoration. A key benefit seems to be their ability to tailor their response to the inflammatory environment without compromising the host ability to fight infection. With over 200 clinical trials registered to examine MSC therapy in liver disease and an increasing number of trials of MSC therapy in solid organ transplant recipients, there is increasing consideration for their use in liver transplantation. In this review we critically appraise the potential role of MSC therapy in the context of liver transplantation, including their ability to modulate reperfusion injury, their role in the reduction of medium term complications in the biliary tree and their potential to enhance tolerance in transplanted organs.

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“…Three meta-analyses[9-11] were published prior to the date of submission by Lan et al[1]. Two further meta-analyses have been published since this date[12,13]. In each case where any of the three studies discussed have been included in another meta-analyses the authors have concluded that the studies have been subject to duplicate publication.…”

Section: To the Editormentioning

confidence: 99%

Duplicate publication bias weakens the validity of meta-analysis of immunosuppression after transplantation

Fairfield

Wigmore

2017

WJG

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Duplicate publication can introduce significant bias into a meta-analysis if studies are inadvertently included more than once. Many studies are published in more than one journal to maximize readership and impact of the study findings. Inclusion of multiple publications of the same study within a meta-analysis affords inappropriate weight to the duplicated data if reports of the same study are not linked together. As studies which have positive findings are more likely to be published in multiple journals this leads to a potential overestimate of the benefits of an intervention. Recent advances in immunosuppression strategies following liver transplantation have led to many studies investigating immunosuppressive regimes including immunosuppression monotherapy. In this letter we focus on a recently published meta-analysis by Lan et al investigating studies assessing immunosuppression monotherapy for liver transplantation. The authors claim to have identified fourteen separate randomised studies investigating immunosuppression monotherapy. Seven of the references appear to relate to only three studies which have been subject to duplicate publication. Several similarities can be identified in each of the duplicate publications including similar authorship, identical immunosuppression regimes, identical dates of enrolment and citation of the original publication in the subsequent manuscripts. We discuss the evidence of the duplicate publication inclusion in the meta-analysis.

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Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted patients

Cited by 21 publications

References 123 publications

Current status of glucocorticoid usage in solid organ transplantation

Current status of glucocorticoid usage in solid organ transplantation

Mesenchymal Stromal Cells, a New Player in Reducing Complications From Liver Transplantation?

Duplicate publication bias weakens the validity of meta-analysis of immunosuppression after transplantation

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