Immunosuppression in liver transplant Di Maira, Tommaso; Little, Ester Coelho; Berenguer, Marina
Baillière's best practice & research. Clinical gastroenterology,
June-August 2020, 2020 Jun - Aug, 2020-06-00, 20200601, Letnik:
46-47
Journal Article
Recenzirano
The increasing potency of immunosuppression (IS) agents resulted in significantly decreased rates of steroid resistant rejection and rejection related graft loss in liver transplantation (LT). ...Currently, more than two thirds of late mortality after LT is unrelated to graft function. However, the increased benefit of more potent IS drugs, coupled with the prolonged survival of transplant recipients led to longer patients exposure to these drugs and their unwanted adverse effects, creating a double-edged sword.
In this article the authors describe the mechanism of action and the adverse effects of the most commonly used immunosuppressed drugs, and the most commonly used IS regimens for both induction and maintenance regimens.
The balance between the ideal IS regimen to prevent rejection and the need to minimize the dose of IS drugs in order to prevent the adverse effects related to its use requires the knowledge of the science and the experience with the art of medicine. The different protocols aimed at protecting renal function and preventing the development of de novo cancer and metabolic syndrome are discussed here.
The main causes of mortality late after liver transplant are associated with prolonged use of IS medications, and clear evidence exists about over-immunosuppression of recipients of liver transplant. The current status of strategies of IS minimization and withdrawal are reviewed in this article, with evaluation of its benefits and pitfalls.
Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of ...CDI among kidney transplant (KT) recipients.
Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression.
A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without.
We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management.
•Prevalence of CDI among hospitalized patients with a history of kidney transplant in the US is 2.4%.•CDI was associated with worse outcomes among kidney transplant recipients.•CDI was associated with higher resource utilization among kidney transplant recipients.•CDI did not confer an increased risk of kidney transplant rejection or failure.
The optimal level of immunosuppression in solid organtransplantation, in particular for the liver, is a delicatebalance between the benefit of preventing rejection andthe adverse side effects of ...immunosuppression. Thereis uncertainty about when this level is achieved in anyindividual recipient. Immunosuppression regimens varybetween individual centers and changes with time as new agents and data are available. Presently concernsabout the adverse side effects of calcineurin inhibitor,the main class of immunosuppressive agents used inliver transplantation （LT）, has led to consideration of theuse of antibody induction therapies for patients at higherrisk of developing adverse side effects. The longevityof the transplanted organ is potentially improved bybetter management of rejection episodes and specialconsideration for tailoring of immunosuppression to theindividual with viral hepatitis C, hepatocellular carcinomaor pregnancy. This review provides an overview of thecurrent strategies for post LT immunosuppression anddiscusses modifications to consider for special patientpopulations.
Summary Despite the increase in long-term survival, liver transplant recipients still exhibit higher morbidity and mortality than the general population. This is in part attributed to the lifelong ...administration of immunosuppression and its associated side effects. Several studies reported in the last decades have evaluated the impact of immunosuppression minimization in liver transplant recipients, but results have been inconsistent due to the heterogeneity of study designs and insufficient sample sizes. On the other hand, complete immunosuppression withdrawal has proven to be feasible in approximately 20% of carefully selected liver transplant recipients, especially in older patients and those with longer duration after transplantation. The long-term risks and clinical benefits of this strategy, however, also need to be clarified. As a consequence, and despite the general perception that a large proportion of liver recipients are over-immunosuppressed, it is currently not possible to derive evidence-based guidelines on how to manage long-term immunosuppression to improve clinical outcomes. Large clinical trials of drug minimization and/or withdrawal focused on clinically-relevant long-term outcomes are required. Development of personalized medicine tools and a deeper understanding of the pathogenesis of idiopathic inflammatory graft lesions will be pre-requisites to achieve these goals.
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