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Hussaini, Trana; Turgeon, Ricky D.; Partovi, Nilufar; Erb, Siegfried R.; Scudamore, Charles H.; Yoshida, Eric M.

doi:10.6002/ect.2017.0096

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…This survey suggests that transplantation centers are worried about graft rejection, perhaps in the light of the previous weaning studies and thus do not perform immunosuppression discontinuation. 61 In our routine practice, each patient receives an individualized combination therapy, which may be minimized without being totally discontinued. Intravenous methylprednisolone is administered from postoperative day 1-5 in tapering doses and then 30 mg per oral (PO) is administered by postoperative day 6.…”

Section: Long -Term Immunosuppressionmentioning

confidence: 99%

Update on Immunosuppression in Liver Transplantation

Taşdoğan

Şimşek

et al. 2017

Euroasian Journal of Hepato-Gastroenterology

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The standard therapy for decompensated end-stage chronic liver disease of any etiology and acute fulminant hepatic failure is liver transplantation (LT). Advances in immunosuppressive therapy decreased the rates of acute and chronic rejections. Thus, graft and patient survivals have significantly improved. However, long-term adverse effects of prolonged use of immunosuppressive agents such as malignancies, opportunistic infections, metabolic disorders, and other organ toxicities have now become a major concern. Consequently, alternative approaches are needed to deescalate the customary drugs and their side effects. Therapy must be individualized and additional preventive measures should be taken by patients with particular risk factors or predisposed to certain adverse effects. Current opinion favors a combination of agents with different mechanism of actions and toxicity profiles. Corticosteroids are employed in immediate and early postoperative period. Although they have a pronounced side effect profile, calcineurin inhibitors (CNIs) are still the backbone of early and late phase immunosuppressive regimens because of their proved efficacy. Antimetabolites are frequent choices for steroid and/or CNI-sparing strategies. Studies also have established a role for mammalian target of rapamycin (mTOR) inhibitors in specific groups of recipients. Biologic agents are a hot topic of interest and made their way into current strategies for induction. Agents extrapolated from other transplantation or immunologic experience are being evaluated.

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Section: Long -Term Immunosuppressionmentioning

confidence: 99%

Update on Immunosuppression in Liver Transplantation

Taşdoğan

Şimşek

et al. 2017

Euroasian Journal of Hepato-Gastroenterology

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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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Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

et al. 2021

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Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed. Harnessing the power of the immune system has shown promise in certain autoimmunity and cancer settings. In the context of the liver, regulatory T cell (Treg) therapies are in development. The hypothesis is that these specialized lymphocytes that dampen inflammation may reduce liver injury in patients with chronic, progressive diseases, and promote transplant tolerance. Various strategies including intrinsic and extracorporeal expansion of Treg cells, aim to increase their abundance to suppress immune responses. We recently discovered that hepatocytes engulf and delete Treg cells by enclysis. Herein, we propose that inhibition of enclysis may potentiate existing regulatory T cell therapeutic approaches in patients with autoimmune liver diseases and in patients receiving a transplant. Moreover, in settings where the abundance of Treg cells could hinder beneficial immunity, such us in chronic viral infection or liver cancer, enhancement of enclysis could result in transient, localized reduction of Treg cell numbers and tip the balance towards antiviral and anti-tumor immunity. We describe enclysis as is a natural process of liver immune regulation that lends itself to therapeutic targeting, particularly in combination with current Treg cell approaches.

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Untitled

Cited by 3 publications

References 15 publications

Update on Immunosuppression in Liver Transplantation

Update on Immunosuppression in Liver Transplantation

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

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

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