scholarly journals Unexpectedly High Efficacy of SARS-CoV-2 BNT162b2 Vaccine in Liver versus Kidney Liver Transplant Recipients—Is It Related to Immunosuppression Only?

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1454
Author(s):  
Paulina Nazaruk ◽  
Marta Monticolo ◽  
Anna Maria Jędrzejczak ◽  
Natalia Krata ◽  
Barbara Moszczuk ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Trough Level ◽  
Severe Disease ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Immunosuppressive Drug ◽  
Transplant Recipients ◽  
Igg Antibody ◽  
Protective Antibodies ◽  
Liver Transplant Recipients

The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 μg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4–6 weeks after the first dose and 4–8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.

scholarly journals Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients

2020 ◽  
Vol 9 (9) ◽  
pp. 2897
Author(s):  
Jong Man Kim ◽  
Je Ho Ryu ◽  
Kwang-Woong Lee ◽  
Suk Kyun Hong ◽  
Kwangho Yang ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Extended Release ◽  
Trough Level ◽  
Pharmacokinetic Analysis ◽  
Transplant Recipients ◽  
Open Label ◽  
Once Daily ◽  
Transplant Patients ◽  
Liver Transplant Recipients ◽  
Cyp3a5 Polymorphism

Cytochrome P450 (CYP) 3A5 polymorphism influences tacrolimus metabolism, but its effect on the drug pharmacokinetics in liver transplant recipients switched to once-daily extended-release formulation remains unknown. The aim of this study is to analyze the effect of CYP3A5 polymorphism on liver function after once-daily tacrolimus conversion in liver transplant patients. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (p = 0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (−42.9% vs. −26.1%) and dose/kg-adjusted trough level of tacrolimus (−40.0% vs. −23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. A pharmacokinetic analysis was performed in 10 patients and tacrolimus absorption in the non-expressor group was slower than in the expressor group. In line with this observation, the area under the curve for once-daily tacrolimus correlated with trough level (Cmin) in the non-expressors and peak concentration (Cmax) in the expressors. CYP3A5 genotyping in liver transplant recipients leads to prediction of pharmacokinetics after switching from a twice-daily regimen to a once-daily dosage form, which makes it possible to establish an appropriate dose of tacrolimus.

scholarly journals Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients

Hepatology ◽  
2013 ◽  
Vol 58 (5) ◽  
pp. 1824-1835 ◽  
Author(s):  
Carlos Benítez ◽  
María-Carlota Londoño ◽  
Rosa Miquel ◽  
Tommaso-Maria Manzia ◽  
Juan G. Abraldes ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Transplant ◽  
Drug Withdrawal ◽  
Immunosuppressive Drug ◽  
Multicenter Clinical Trial ◽  
Transplant Recipients ◽  
Adult Liver ◽  
Liver Transplant Recipients

scholarly journals Low IgG antibody levels against SARS‐CoV‐2 after two‐dose vaccination among liver transplant recipients

2021 ◽  
Author(s):  
Jimena Prieto ◽  
Florencia Rammauro ◽  
Martín López ◽  
Romina Rey ◽  
Ana Fernández ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Transplant Recipients ◽  
Igg Antibody ◽  
Antibody Levels ◽  
Liver Transplant Recipients

scholarly journals Humoral response to SARS-CoV-2 infection among liver transplant recipients

Gut ◽  
2022 ◽  
pp. gutjnl-2021-326609
Author(s):  
Chiara Becchetti ◽  
Annelotte G C Broekhoven ◽  
Géraldine Dahlqvist ◽  
Montserrat Fraga ◽  
Marco Fabrizio Zambelli ◽  
...  
Keyword(s):  
Antibody Response ◽  
Liver Transplant ◽  
Immunosuppressive Agents ◽  
Humoral Response ◽  
Transplant Recipients ◽  
Antibody Testing ◽  
Index Level ◽  
Matching Criteria ◽  
Liver Transplant Recipients ◽  
Control Study

ObjectiveImmunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19.DesignProspective multicentre case–control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT).ResultsOverall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024).ConclusionsOur findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.

scholarly journals Dose-adjusted and dose/kg-adjusted concentrations of mycophenolic acid precursors reflect metabolic ratios of their metabolites in contrast with tacrolimus and cyclosporine

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Ewa Hryniewiecka ◽  
Jolanta Żegarska ◽  
Dorota Żochowska ◽  
Emilia Samborowska ◽  
Radosław Jaźwiec ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Kidney Transplant ◽  
Mycophenolic Acid ◽  
Parent Drug ◽  
Immunosuppressive Drug ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Liver And Kidney ◽  
Liver Transplant Recipients

Abstract Background and purpose: Therapeutic drug monitoring is a valuable tool supporting immunosuppressive therapy. Significant variation of immunosuppressive drug (ISD) concentrations during their use at similar doses is the basis of dose-normalization strategy. The strategy of dose-adjustment is proposed to identify variability in the rate of ISD metabolism. While the parent drug-to-metabolite ratio (metabolic ratio, MR) represents the rate of formation of individual metabolites. The present study was aimed at evaluation of associations between ISDs’ metabolism rate expressed as dose-adjusted concentrations (C/D) and dose/kg-adjusted concentrations (C/D/kg) and MRs of individual metabolites of tacrolimus, cyclosporine A and MPA precursors. Experimental approach: 506 patients have participated: 284 males (56.13%) and 222 females (43.87%); 318 after kidney (62.85%) and 188 after liver transplantation; median age was 51.34 (39.32-59.95) years and median time after transplantation 78.92 (33.87-138.4) months. Key results: Generally, we have not observed significant relationships between dose-adjusted and dose/kg-adjusted concentrations and MRs of cyclosporine and tacrolimus. Significant correlations were found for: AM9/CsA and dMC-CsA/CsA in kidney transplant recipients and MIII/Tac, AM1/CsA and AM4N/CsA in liver transplant recipients. In contrast, MRs of mycophenolic acid (MPA) metabolites correlated significantly with MPA C/D and C/D/kg both in kidney and liver transplant recipients. Conclusion and implications: In conclusion, easily available and easy to use in clinical practice C/D and C/D/kg ratios cannot be considered as parameters directly reflecting the rate of generation of major metabolites of cyclosporine and tacrolimus both in liver and kidney transplant recipients.

scholarly journals Effect of CYP3A5 Polymorphism on Liver Function and Tacrolimus Pharmacokinetics after Conversion to a Once-Daily Tacrolimus Formulation in Stable Liver Transplant Patients

2020 ◽  
Author(s):  
Jong Man Kim ◽  
Je Ho Ryu ◽  
Kwang-Woong Lee ◽  
Suk Kyun Hong ◽  
Kwangho Yang ◽  
...  
Keyword(s):  
Liver Function ◽  
Liver Transplant ◽  
Extended Release ◽  
Trough Level ◽  
Daily Regimen ◽  
Transplant Recipients ◽  
Once Daily ◽  
Liver Transplant Recipients ◽  
Tacrolimus Pharmacokinetics ◽  
Cyp3a5 Polymorphism

To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.

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