scholarly journals Strategies to Improve Immune Suppression Post-Liver Transplantation: A Review

2021 ◽  
Vol 2 (4) ◽  
pp. 441-454
Author(s):  
Islam B Mohamed ◽  
Fuad Z Aloor ◽  
Prasun K Jalal
Keyword(s):  
Liver Transplantation ◽  
Graft Loss ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Neurological Complications ◽  
Immunosuppressive Agent ◽  
Post Transplantation ◽  
Immunosuppressive Medications ◽  
Medication Side ◽  
Clinical Dilemma

Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.

Liver transplantation

2020 ◽  
pp. 3100-3107
Author(s):  
John G. O’Grady
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Antiviral Agents ◽  
Graft Loss ◽  
Graft Function ◽  
Myeloproliferative Disease ◽  
Direct Acting Antiviral ◽  
Tumour Bulk ◽  
Technical Complication ◽  
End Stage

Liver transplantation is an established treatment for liver conditions that broadly fall into the categories of acute liver failure, end-stage chronic liver disease, primary hepatic malignancy, and metabolic disease. The expected 1-year survival rate is over 90% and some patients are alive more than 40 years after transplantation. Disease severity scores for cirrhosis heavily influence selection of patients with cirrhosis for transplantation. The prototype is the MELD (Model for End-Stage Liver Disease) score, based on serum bilirubin, serum creatinine, and INR: a score of 16 is considered the threshold that confers benefit from liver transplantation. Hepatocellular carcinoma accounts for most of the malignancy group and selection is largely determined by tumour bulk assessed by the number and size of lesions. Immunosuppression strategies based on tacrolimus, with or without other drugs including mTOR (mechanistic target of rapamycin) inhibitors, antiproliferative agents, or prednisolone, are highly effective in preventing loss of the graft through classical rejection processes. Recurrence of original disease is the main cause of loss of graft function, with recurrence of hepatitis C a particularly challenging problem, although new direct-acting antiviral agents are likely to radically improve outcomes. Technical problems can also result in graft loss due to hepatic artery thrombosis or diffuse ischaemic cholangiopathy, especially in livers harvested from donors after cardiac death. Anastomotic biliary strictures are the commonest technical complication, with 15 to 20% of patients requiring some form of endoscopic or surgical intervention. There is a considerably increased risk of myeloproliferative disease and skin cancers in transplant recipients, as well as aetiology-specific risk. Many patients die having achieved a normal life expectancy, and death with a functioning graft is the commonest terminal scenario.

scholarly journals Diffusion MRI Findings in Encephalopathy Induced by Immunosuppressive Therapy after Liver Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Emanuele Tinelli ◽  
Nicoletta Locuratolo ◽  
Alberto Pierallini ◽  
Massimo Rossi ◽  
Francesco Fattapposta
Keyword(s):  
Liver Transplantation ◽  
Immunosuppressive Therapy ◽  
Cyclosporine A ◽  
Early Recognition ◽  
Brain Mri ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Neurological Complications ◽  
Solid Organ ◽  
Diffusion Weighted Images

Neurological complications are common after liver transplantation, as they affect up to one-third of the transplanted patients and are associated with significant morbidity. The introduction of calcineurin inhibitors, cyclosporine A and tacrolimus, in immunosuppressive regimens significantly improved the outcome of solid-organ transplantation even though immunosuppression-associated neurotoxicity remains a significant complication, particularly occurring in about 25% of cases after liver transplantation. The immunosuppressant cyclosporine A and tacrolimus have been associated with the occurrence of major neurological complications, diffuse encephalopathy being the most common. The biochemical and pathogenetic basis of calcineurin inhibitors-induced neurotoxicity are still unclear although several mechanisms have been suggested. Early recognition of symptoms could help reduce neurotoxic event. The aim of the study was to evaluate cerebral changes through MRI, in particular with diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps, in two patients undergoing liver transplantation after immunosuppressive therapy. We describe two patients in which clinical pictures, presenting as a severe neurological condition, early after orthotopic liver transplantation during immunosuppression therapy, showed a different evolution in keeping with evidence of focal-multifocal lesions at DWI and ADC maps. At clinical onset, DWI showed hyperintensity of the temporo-parieto-occipital cortex with normal ADC values in the patient with following good clinical recovery and decreased values in the other one; in the latter case, MRI abnormalities were still present after ten days, until the patient’s exitus. The changes in DWI with normal ADC may be linked to brain edema with a predominant vasogenic component and therefore reversible, while the reduction in ADC is due to cytotoxic edema and linked to more severe, nonreversible, clinical picture. Brain MRI and particularly DWI and ADC maps provide not only a good and early representation of neurological complications during immunosuppressant therapy but can also provide a useful prognostic tool on clinical outcome of the patient.

scholarly journals Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7274 ◽  
Author(s):  
Hui-Ying Liu ◽  
Yuan-Tso Cheng ◽  
Hao Lun Luo ◽  
Chiang-Chi Huang ◽  
Chien Hsu Chen ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Induction Therapy ◽  
Dose Regimen ◽  
Low Dose ◽  
Graft Loss ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Kidney Transplant Recipients ◽  
Significant Difference ◽  
Kidney Transplantations

Background Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. Methods We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. Results There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. Discussion In recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

scholarly journals Hemodynamics in renal transplant in children with various morphological changes in the long-term post-transplant period

2021 ◽  
pp. 286-293
Author(s):  
Denis B. Ektov ◽  
Mikhail I. Pykov ◽  
Alexey L. Valov ◽  
Maria S. Molchanova ◽  
Berta L. Kushnir ◽  
...  
Keyword(s):  
Renal Artery ◽  
Morphological Changes ◽  
Objective Assessment ◽  
Graft Function ◽  
Resistance Index ◽  
Calcineurin Inhibitors ◽  
Nitrogen Excretion ◽  
Post Transplantation ◽  
Morphological Studies ◽  
The Common

Introduction. Ultrasound scanning is one of the main methods of instrumental examination of patients after allogenic transplantation of kidney. The main reasons of dysfunction of the kidney transplant in long post-transplantation term are acute or chronic rejection, as well as acute and chronic nephrotoxicity of calcineurin inhibitors.Objective. Assessment of dopplerographic indicators of the blood flow throughout the transplanted kidney vessels in patients with preserved nitrogen excretion function under various morphological changes.Materials and methods. The study includes an analysis of the medical history of 98 children with end-stage chronic renal failure who underwent 98 allogeneic kidney transplants from a posthumous donor. There were analyzed the results of 185 percutaneous puncture biopsies and ultrasound studies of renal transplants. The analyzed data of morphological studies are divided into 4 groups. 1st group – there are no morphological changes affecting graft function. 2nd group – morphological signs of calcineurin toxicity. 3rd group – borderline damage of the graft. 4th group – acute and chronic graft rejection.Results and discussion. Indices of resistance and pulsation measured at the level of the renal artery and interlobular arteries tended to decrease in the kidneys with immunological influence and remained stable in other morphological groups. This means that, the higher the degree of hyalinosis of the arteries, the lower the indices of resistance and pulsation indices measured at the level of the common renal artery and interlobular arteries.Conclusions. The revealed tendency of a decrease in the values of the resistance index and the pulsation index at the level of the common renal artery of the interlobular arteries can be considered as one of the initial ultrasound signs that allow to speak of a decrease in the elasticity of the vascular wall. Normal indices of renal hemodynamics do not exclude the presence of pathological processes leading to graft dysfunction.

scholarly journals Successful treatment of BK virus associated-nephropathy in a human immunodeficiency virus-positive kidney transplant recipient

2020 ◽  
Vol 31 (4) ◽  
pp. 387-391 ◽  
Author(s):  
Gaetano Alfano ◽  
Francesco Fontana ◽  
Giovanni Guaraldi ◽  
Gianni Cappelli ◽  
Cristina Mussini
Keyword(s):  
Transplant Recipient ◽  
Kidney Transplant ◽  
Successful Treatment ◽  
Kidney Transplant Recipient ◽  
Graft Loss ◽  
Graft Function ◽  
Opportunistic Pathogen ◽  
Bk Virus ◽  
Kidney Transplant Recipients ◽  
Post Transplantation

BK virus (BKV) is an opportunistic pathogen in those with impaired immunity. Viral replication is generally asymptomatic but is able to induce cytopathic alterations in renal cells. If BKV infection is left untreated, it leads to BKV-associated nephropathy (BKVAN) and graft loss. There is scarce experience in the management of BKV infection in kidney transplant recipients living with HIV. We report the successful treatment of BKVAN in an HIV-positive kidney transplant recipient who experienced BKV replication in the immediate post-transplantation period. A change in therapy from calcineurin inhibitor to sirolimus, steroid withdrawal and a short course of an immunomodulatory agent (leflunomide) controlled BKV viremia in the absence of drug side-effects or impairment of graft function.

scholarly journals PREVALENCE AND TIME OF DEVELOPMENT OF SYSTEMIC ARTERIAL HYPERTENSION IN PATIENTS AFTER LIVER TRANSPLANTATION

2021 ◽  
Vol 58 (1) ◽  
pp. 77-81
Author(s):  
Bianca de Oliveira LEMOS ◽  
Rita de Cássia Martins Alves SILVA ◽  
Renato Ferreira da SILVA
Keyword(s):  
Metabolic Syndrome ◽  
Liver Transplantation ◽  
Arterial Hypertension ◽  
Calcineurin Inhibitors ◽  
Immunosuppressive Drugs ◽  
Immunosuppressive Drug ◽  
University Hospital ◽  
Post Transplantation ◽  
Systemic Arterial Hypertension ◽  
High Prevalence

ABSTRACT BACKGROUND: The use of immunosuppressive drugs after liver transplantation (LT) is associated with the development of systemic arterial hypertension (SAH), in addition to other comorbidities of metabolic syndrome. OBJECTIVE: Therefore, the purpose of this study was to analyze the time after use immunosuppressive drugs the patient progresses to SAH, as well as to identify its prevalence and the factors that may be correlated to it. METHODS: A retrospective and longitudinal study was conducted, based on the analysis of medical records of 72 normotensive patients, attended in the transplant unit of a university hospital, between 2016 and 2019. RESULTS: It was observed, on average, 9±6.98 months after immunosuppressive use, the patients were diagnosed with hypertension, and the prevalence of transplanted patients who evolved to SAH in this study was 59.64% (41 patients). In addition, there was a correlation between serum dosage of tacrolimus and the development of SAH (P=0.0067), which shows that tacrolimus has a significant role in the development of SAH. Finally, it was noticed that the development of post-transplantation hypertension indicates a higher risk of the patient presenting the other parameters of metabolic syndrome, as well as a higher impairment in its renal function (P=0.0061). CONCLUSION: This study shows that the patients evolved to SAH in an average of 9±6.98 months after immunosuppressive drug use. We have also found high prevalence of systemic arterial hypertension (59.64%) in patients after liver transplantation, who used calcineurin inhibitors, especially when associated with the use of tacrolimus.

scholarly journals Tolerance and chronic rejection

2001 ◽  
Vol 356 (1409) ◽  
pp. 727-738 ◽  
Author(s):  
Karl L. Womer ◽  
Richard S. Lee ◽  
Joren C. Madsen ◽  
Mohamed H. Sayegh
Keyword(s):  
Chronic Rejection ◽  
Graft Function ◽  
Experimental Studies ◽  
Tolerance Induction ◽  
Allograft Survival ◽  
Post Transplantation ◽  
Immunosuppressive Medications ◽  
Allograft Loss ◽  
Large Animals

The most common cause of chronic allograft loss is an incompletely understood clinicopathological entity called chronic rejection (CR). Recent reports suggest an improvement in long–term renal allograft survival, although it is not clear from these data whether a true reduction of biopsy–proven CR has occurred. Although newer immunosuppressive medications have greatly reduced the incidence of acute rejection (AR) in the early post–transplantation period, the ideal therapy for both AR and CR would be to achieve a state of tolerance. By definition, such a state should allow for indefinite allograft survival, with no histopathological evidence of CR, despite immunocompetence in the host (i.e. without the need for chronic immunosuppression). Although several experimental studies are able to achieve tolerance, with clear improvement in allograft survival, detailed studies on graft function and morphology are often not included. This review will discuss possible ways that tolerance induction could lead to a CR–free state. General mechanisms of CR and transplantation tolerance induction are discussed as well as the difficulties in translating small animals studies into large animals and humans.

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

scholarly journals The future is coming: promising perspectives regarding the use of machine learning in renal transplantation

2019 ◽  
Vol 41 (2) ◽  
pp. 284-287
Author(s):  
Pedro Guilherme Coelho Hannun ◽  
Luis Gustavo Modelli de Andrade
Keyword(s):  
Machine Learning ◽  
Prediction Models ◽  
Graft Function ◽  
Statistical Technique ◽  
Daily Routine ◽  
Learning Approaches ◽  
Post Transplantation ◽  
Chronic Allograft Rejection ◽  
Institutional Experience ◽  
Learning Principles

Abstract Introduction: The prediction of post transplantation outcomes is clinically important and involves several problems. The current prediction models based on standard statistics are very complex, difficult to validate and do not provide accurate prediction. Machine learning, a statistical technique that allows the computer to make future predictions using previous experiences, is beginning to be used in order to solve these issues. In the field of kidney transplantation, computational forecasting use has been reported in prediction of chronic allograft rejection, delayed graft function, and graft survival. This paper describes machine learning principles and steps to make a prediction and performs a brief analysis of the most recent applications of its application in literature. Discussion: There is compelling evidence that machine learning approaches based on donor and recipient data are better in providing improved prognosis of graft outcomes than traditional analysis. The immediate expectations that emerge from this new prediction modelling technique are that it will generate better clinical decisions based on dynamic and local practice data and optimize organ allocation as well as post transplantation care management. Despite the promising results, there is no substantial number of studies yet to determine feasibility of its application in a clinical setting. Conclusion: The way we deal with storage data in electronic health records will radically change in the coming years and machine learning will be part of clinical daily routine, whether to predict clinical outcomes or suggest diagnosis based on institutional experience.

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