Dataset Information

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

ABSTRACT:

Purpose

Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand ¹⁸F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression.

Methods

PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-dose CNI, 10 with standard-dose CNI immunosuppression) and 9 healthy controls. The total distribution volume (V_T) estimated in 12 volumes-of-interest was analyzed regarding TSPO genotype, CNI therapy, and cognitive performance.

Results

In controls, V_T was about 80% higher in high affinity binders (n = 5) compared to mixed affinity binders (n = 3). Mean V_T corrected for TSPO genotype was significantly lower in patients compared to controls, especially in patients in whom CNI dose had been reduced because of nephrotoxic side effect.

Conclusion

Our results provide evidence of chronic suppression of microglial activity in liver-transplanted patients under CNI therapy especially in patients with high sensitivity to CNI toxicity.

SUBMITTER: Dirks M

PROVIDER: S-EPMC8712291 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

Dirks Meike M Buchert Ralph R Wirries Ann-Katrin AK Pflugrad Henning H Grosse Gerrit M GM Petrusch Carlotta C Schütze Christian C Wilke Florian F Mamach Martin M Hamann Linda L Langer Laura B N LBN Ding Xiao-Qi XQ Barg-Hock Hannelore H Klempnauer Jürgen J Wetzel Christian H CH Lukacevic Mario M Janssen Eike E Kessler Mariella M Bengel Frank M FM Geworski Lilli L Rupprecht Rainer R Ross Tobias L TL Berding Georg G Weissenborn Karin K

European journal of nuclear medicine and molecular imaging 20210512 1

<h4>Purpose</h4>Calcineurin inhibitors (CNI) can cause long-term impairment of brain function. Possible pathomechanisms include alterations of the cerebral immune system. This study used positron emission tomography (PET) imaging with the translocator protein (TSPO) ligand <sup>18</sup>F-GE-180 to evaluate microglial activation in liver-transplanted patients under different regimens of immunosuppression.<h4>Methods</h4>PET was performed in 22 liver-transplanted patients (3 CNI free, 9 with low-d ...[more]

PMID: 33978829

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Project description:BackgroundPatients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, omega-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation.Methods/designA randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality.DiscussionFormulas enriched with arginine, omega-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect.Trial registrationClinicalTrials.gov NCT00495859.

Project description:ObjectivesTo investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice.DesignRetrospective multicentrer cohort study.SettingFour Italian regions (Lombardy, Veneto, Lazio, Sardinia).MethodsData were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI).Main outcome measuresMortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use.ResultsThe study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65).ConclusionsThe study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients.

Dataset Information

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

Purpose

Methods

Results

Conclusion

Publications

Reduced microglia activity in patients with long-term immunosuppressive therapy after liver transplantation.

Similar Datasets

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