Immunosuppressive Drugs in Liver Transplant: An Insight

Panackel, Charles; Mathew, Joe Francis; N, Mohamed Fawas; Jacob, Mathew

doi:10.1016/j.jceh.2022.06.007

Cited by 34 publications

(24 citation statements)

References 111 publications

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“…15 Nowadays, most transplant patients receive conditioning with anti-thymocyte globulin (ATG), basiliximab, or intraoperative alemtuzumab and steroids. 16,17 Post-transplant therapy is primarily T-cell-specific immunosuppressants, particularly calcineurin inhibitors. 14,15,17 The calcineurin inhibitor tacrolimus is used as maintenance therapy in most patients, with additional agents such as steroids, cyclosporine A, azathioprine, mycophenolate mofetil, everolimus, or a mammalian target of rapamycin inhibitor, usually used after an episode of rejection.…”

Section: Liver Tr Ans Pl Antationmentioning

confidence: 99%

Live‐attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation

Keutler,

Lainka,

Posovszky

2024

Pediatric Transplantation

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BackgroundInfections are a serious short‐ and long‐term problem after pediatric organ transplantation. In immunocompromised patients, they can lead to transplant rejection or a severe course with a sometimes fatal outcome. Vaccination is an appropriate means of reducing morbidity and mortality caused by vaccine‐preventable diseases. Unfortunately, due to the disease or its course, it is not always possible to establish adequate vaccine protection against live‐attenuated viral vaccines (LAVVs) prior to transplantation. LAVVs such as measles, mumps, and rubella (MMR) are still contraindicated in solid organ transplant recipients receiving immunosuppressive therapy (IST), thus creating a dilemma.AimThis review discusses whether, when, and how live‐attenuated MMR vaccines can be administered effectively and safely to pediatric liver transplant recipients based on the available data.Material and MethodsWe searched PubMed for literature on live‐attenuated MMR vaccination in pediatric liver transplantation (LT).ResultsNine prospective observational studies and three retrospective case series were identified in which at least 833 doses of measles vaccine were administered to 716 liver transplant children receiving IST. In these selected patients, MMR vaccination was well tolerated and no serious adverse reactions to the vaccine were observed. In addition, an immune response to the vaccine was demonstrated in patients receiving IST.ConclusionDue to inadequate vaccine protection in this high‐risk group, maximum efforts must be made to ensure full immunization. MMR vaccination could also be considered for unprotected patients after LT receiving IST following an individual risk assessment, as severe harm from live vaccines after liver transplantation has been reported only very rarely. To this end, it is important to establish standardized and simple criteria for the selection of suitable patients and the administration of the MMR vaccine to ensure safe use.

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Section: Liver Tr Ans Pl Antationmentioning

confidence: 99%

Live‐attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation

Keutler,

Lainka,

Posovszky

2024

Pediatric Transplantation

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“…T-cell specific antibody induction has been investigated to minimize corticosteroids in liver transplant recipients 1 , 6 . Induction immunosuppression using T-cell specific antibodies is now available and is used in approximately one-third of liver transplant recipients during the past decade 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Induction immunosuppression using T-cell specific antibodies is now available and is used in approximately one-third of liver transplant recipients during the past decade 7 . T-cell specific antibodies used for induction immunosuppression include interleukin-2 receptor antagonists (daclizumab, or basiliximab), monoclonal antibodies specific for the CD3 receptor (muromonab-CD3) or the CD52 surface protein (alemtuzumab), and polyclonal antibodies (rabbit or horse anti-thymocyte globulin (ATG)) 6 .…”

Section: Introductionmentioning

confidence: 99%

T-cell specific antibody induction versus corticosteroid induction immunosuppression for liver transplant recipients: a meta-analysis

Jung

Kuh

Lim

et al. 2023

Sci Rep

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Corticosteroids remain the mainstay of immunosuppression for liver transplant recipients despite several serious complications including infection, hepatitis C virus (HCV) recurrence, diabetes mellitus (DM), and hypertension. We attempted to compare the safety and efficacy of T-cell specific antibody induction with complete corticosteroid avoidance. We searched MEDLINE, EMBASE, and Cochrane central library. Randomized controlled trials comparing T-cell specific antibody induction with corticosteroid induction immunosuppression were included. Our primary outcome was the incidence of biopsy-proven acute rejection. Eleven trials involving 1683 patients were included. The incidence of acute rejection was not significantly different between the antibody and steroid induction groups (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.72, 1.01, P = 0.06, I2 = 0%). However, T-cell specific antibody induction significantly reduced the risk of cytomegalovirus infection (RR 0.48, 95% CI 0.33, 0.70, P = 0.0002, I2 = 3%), HCV recurrence (RR 0.89, 95% CI 0.80, 0.99, P = 0.03, I2 = 0%), DM (RR 0.41, 95% CI 0.32, 0.54, P < 0.0001, I2 = 0%) and hypertension (RR 0.71, 95% CI 0.55, 0.90, P = 0.005, I2 = 35%). Trial sequential analysis for acute rejection showed that the cumulative z-curve did not cross the Trial sequential boundary and the required information size was not reached. T-cell specific antibody induction compared to corticosteroid induction seems to significantly reduce opportunistic infections including cytomegalovirus infection and HCV recurrence and metabolic complications including DM and hypertension. However, given the insufficient study power, low quality of evidence, and heterogeneous immunosuppressive regimens, our results should be cautiously appreciated.

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“…Nevertheless, a large number of patients show immune rejection after LT and have to take a longterm administration of immunosuppressive agents, such as calcineurin inhibitors (e.g., tacrolimus), antimetabolite inhibitors (e.g., azathioprine and mycophenolate mofetil), and corticosteroids [4][5][6]. These agents often lead to various adverse events such as nephrotoxicity, metabolic disorders, and primary malignancies [7]. Therefore, it is urgent to find alternatives for immunosuppressants, with an aim to attenuate the immunosuppressant-induced adverse events.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

Li,

Yu,

Chen

et al. 2023

Dig Dis

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Background: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants. Summary: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT. Key messages: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

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Immunosuppressive Drugs in Liver Transplant: An Insight

Cited by 34 publications

References 111 publications

Live‐attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation

Live‐attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation

T-cell specific antibody induction versus corticosteroid induction immunosuppression for liver transplant recipients: a meta-analysis

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

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