Comprehensive risk assessment for early neurologic complications after liver transplantation

Wu, Seng-Tang; Chen, Teng-Wei; Feng, An‐Chieh; Fan, Huiying; Hsieh, Chung-Bao; Chung, Kuo‐Piao

doi:10.3748/wjg.v22.i24.5548

Cited by 20 publications

(14 citation statements)

References 36 publications

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“…Hypothetically, it may be related to a lower capacity of older livers of metabolizing such drugs. Lue et al's results could be partially in line with those described by Wu et al, who reported that donor age <22 or ≥40 years and graft-recipient weight ratio are associated with neurological complications after LT (9). In this study, that included 295 adult LT recipients (193 of whom received their grafts from living donors), the incidence of neurological complications was 49.3%, with encephalopathy being the most common complication (n=106, 73%).…”

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confidence: 88%

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Neurotoxicity after liver transplantation: does donor age matter?

Sastre

Crespo

2021

Transl Gastroenterol Hepatol

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Early calcineurin inhibitors (CNIs)-induced neurotoxicity is a serious and frequent complication after liver transplantation (LT). It takes place in 6-47% of LT recipients treated with CNI, and it is associated with significant mortality, morbidity, and prolonged hospital stay (1-3). Controversy continues over which patients have a greater risk of developing CNI neurotoxicity after LT (4). The incidence of early CNI neurotoxicity is higher in LT recipients receiving tacrolimus compared with patients receiving cyclosporine (5). Major central nervous system manifestations are diverse, and they are commonly classified as minor (tremor, headache, insomnia, paresthesia), and major (encephalopathy, akinetic mutism, seizures, speech disorders, polyneuropathy, psychosis) (3). Different ways of treating early CNI neurotoxicity have been described, such as a decrease in the dosage of CNI using other immunosuppressant drugs (mycophenolate mofetil or everolimus), switching from tacrolimus to cyclosporine or vice versa, and even CNI withdrawal in the most severe cases (2).Several retrospective studies have investigated the risk factors and possible mechanism of CNI neurotoxicity. Most studies have focused on recipients' risk factors: age, MELD score, ALT, bilirubin, creatinine, glycemia, hypocholesterolemia, hyponatremia, hypomagnesemia, h y p e r t e n s i o n , a l c o h o l c o n s u m p t i o n a n d h e p a t i c encephalopathy (2,3,6) have been shown as potential risk factors for CNI neurotoxicity. In addition, Yamauchi et al. described that a polymorphism in the ABCB1 gene may be a risk factor for tacrolimus induced neurotoxicity in related living donor LT recipients (7). However, few studies have evaluated donor and technical aspects as potential risk factors for CNI-neurotoxicity in liver transplant recipients (8,9).

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confidence: 88%

“…In addition, Yamauchi et al described that a polymorphism in the ABCB1 gene may be a risk factor for tacrolimus induced neurotoxicity in related living donor LT recipients (7). However, few studies have evaluated donor and technical aspects as potential risk factors for CNI-neurotoxicity in liver transplant recipients (8,9).…”

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confidence: 99%

Neurotoxicity after liver transplantation: does donor age matter?

Sastre

Crespo

2021

Transl Gastroenterol Hepatol

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“…Conditions that increase the neurotoxicity of immunosuppressant agents include pre-existing mental disorders [78], hypertension [79], electrolyte disorders including hyper and hyponatremia and hypomagnesemia [37], dysmetabolic alterations, such as hyperglycemia [37], infections that impair the function of the blood–brain barrier (BBB), hypocholesterolemia, which increases the uptake of immunosuppressant drugs in the brain [80], polymorphisms of the adenosine triphosphate (ATP)-binding cassette transporter B1 (ABCB1) gene and cytochrome pigment (CYP) gene, which decrease immunosuppressant efflux or elimination [81,82], drug interactions [82,83], a prolonged surgical period [84], and low liver function or acute liver failure [85].…”

Section: Clinical Features Induced By Different Immunosuppressantsmentioning

confidence: 99%

Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

Zhang

Egashira

Masuda

2019

IJMS

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Although transplantation procedures have been developed for patients with end-stage hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity commonly occurs in clinical practice, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms through which CNIs cause neurotoxicity include increasing the permeability or injury of the blood–brain barrier, alterations of mitochondrial function, and alterations in the electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures, mycophenolate mofetil induces depression and headaches, methotrexate affects the central nervous system, the mouse monoclonal immunoglobulin G2 antibody (used against the cluster of differentiation 3) also induces headaches, and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms help reduce neurotoxic events considerably. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, combination therapy with drugs used to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize recent topics on the mechanisms of immunosuppressive drug-related neurotoxicity. In addition, information about the neuroprotective effects of several immunosuppressants is also discussed.

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“…Conditions that increase the neurotoxicity of immunosuppressant agents include pre-existing mental disorders [78]; hypertension [79]; electrolyte disorders, including hyper-and hyponatremia and hypomagnesemia [37]; dysmetabolic alterations, such as hyperglycaemia [37]; infections that impair the function of the blood-brain barrier (BBB); hypocholesterolaemia, which increases the uptake of immunosuppressant drugs in the brain [80]; polymorphisms of the ATP-binding cassette transporter B1 (ABCB1) gene and cytochrome pigment (CYP) gene, which decrease immunosuppressant efflux or elimination [81,82]; drug interactions [82,83]; a prolonged surgical period [84]; and low liver function or acute liver failure [85].…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

Zhang¹,

Egashira²,

Masuda³

2019

Preprint

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Although transplantation procedures have been developed for patients with end-stagec hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces depression and headache; methotrexate affects the central nervous system; mouse monoclonal immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms have greatly reduced neurotoxic events. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, using drugs to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize the recent topics on the mechanisms of neurotoxicity of immunosuppressive drugs. In addition, some information about neuroprotective effects of several immunosuppressants are also discussed.

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Comprehensive risk assessment for early neurologic complications after liver transplantation

Abstract: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Cited by 20 publications

References 36 publications

Neurotoxicity after liver transplantation: does donor age matter?

Neurotoxicity after liver transplantation: does donor age matter?

Recent Topics on The Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

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