Mycophenolate mofetil discontinuation increases severe acute respiratory syndrome coronavirus 2 vaccine response in nonresponder liver transplantation recipients: A proof of concept

Meunier, Lucy; Malézieux, Emilie; Bedoya, José Ursic; Faure, Stéphanie; Echenne, Maxime; Debourdeau, Antoine; Meszaros, Magdalena; Pageaux, Georges Philippe

doi:10.1002/lt.26569

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…Medication with MMF not only impaired the initial antibody response after administration of the second dose of the SARS-CoV-2 vaccine, but also affected immunogenicity after the booster dose. This impact has already been observed in other studies, and the temporary pause of MMF application for the purpose of vaccine efficacy has already been discussed [ 21 ]. However, despite impairment of the immune response, patients with MMF still developed a significant increase in antibody titers after administration of their third dose, demonstrating the importance of repeated vaccination in this particular patient cohort.…”

Section: Discussionsupporting

confidence: 55%

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients

et al. 2023

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Immunogenicity after SARS-CoV-2 vaccination is known to be impaired in liver transplant (LT) recipients, but the results after the application of a third dose show significant improvement in seroconversion rates. In the general population, the antibody response wanes over the course of time after two doses of the vaccination, but seems to be more robust after the application of three doses. Still, the durability of the antibody response in LT recipients who receive a third dose of SARS-CoV-2 vaccination has not been analyzed yet. We therefore assessed antibody responses in a total of 300 LT recipients and observed antibody titers for six months each after patients had received the second and the third doses of the vaccination, explicitly excluding all patients who had suffered from SARS-CoV-2 infection. The initial antibody response was compared to a control group of 122 healthcare workers. After the application of two doses of the vaccination, 74% of LT recipients (158 out of 213) developed antibodies against SARS-CoV-2; this result depended significantly on whether the patients were taking the medication mycophenolate mofetil, and on the age of the patients. Antibody titers declined significantly within six months from 407 BAU/mL (IQR: 0–1865) to 105 BAU/mL (IQR: 0–145) (p ≤ 0.001), but increased after the application of the third vaccine dose in 92% of patients (105 out of 114), showing an antibody response (p ≤ 0.001). After a further six-month period, despite showing a decline from 2055 BAU/mL (IQR: 500 to >2080) to 1805 BAU/mL (IQR: 517 to >2080), the waning of antibody titers was not significant (p = 0.706), and antibody durability appeared to be more robust than that after the second dose. In conclusion, our study confirms the high efficacy of the application of a third dose of SARS-CoV-2 vaccination in LT recipients, and a reasonably sustained humoral response with superior durability in comparison to antibody kinetics after the application of the second dose of the vaccination.

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Section: Discussionsupporting

confidence: 55%

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients

et al. 2023

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“…For instance, Marion et al [22] reported that patients taking the EVR-TAC combination had improved immune response compared to those taking tacrolimus and mycophenolate. Other studies have confirmed the negative effect of mycophenolate on HR in LT recipients [9,19,21,35]. In this study, we therefore excluded all patients taking mycophenolate and focused on the effect of IS based on TAC and EVR.…”

Section: Discussionmentioning

confidence: 99%

“…Mycophenolate seems to be particularly harmful in this regard, while some studies have reported benefits of maintaining low TAC levels [9,10]. As TAC is the most commonly used IS regimen in LT patients, we sought to further investigate the role of TAC-based IS (TAC-IS) on the immune response to SARS-CoV-2 vaccination.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Humoral Response following SARS-CoV-2 mRNA-Based Vaccination in Liver Transplant Recipients Receiving Tailored Immunosuppressive Therapy

Manzia,

Sensi,

Conte

et al. 2023

JCM

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Background: The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods: This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS). Patients receiving the TAC-EVR combination were divided into two groups based on trough TAC concentrations, i.e., above or below 5 ng/mL. HR (analysed with ECLIA) was assessed at 30 to 135 days after vaccination. The primary outcome was the presence of a positive antibody titre (≥0.8 U/mL). Secondary outcomes were the presence of a highly protective antibody titre (≥142 U/mL), median antibody titre, and incidence of COVID-19. Results: Sixty-one participants were included. Twenty-four (40%) were receiving TAC-IS and thirty-seven (60%) were receiving EVR-IS. At the median follow-up of 116 (range: 89–154) days, there were no significant differences in positive antibody titre (95.8% vs. 94.6%; p = 0.8269), highly-protective antibody titre (83.3% vs. 81.1%; p = 0.8231), median antibody titre (2410 [IQ range 350–2500] vs. 1670 [IQ range 380–2500]; p = 0.9450), and COVID-19 incidence (0% vs. 5.4%; p = 0.5148). High serum creatinine and low estimated glomerular filtration rate were risk factors for a weak or absent HR. Conclusions: Three doses of mRNA-based SARS-CoV-2 vaccination yielded a highly protective HR in LT recipients. The use of TAC or EVR-based IS does not appear to influence HR or antibody titre, while renal disease is a risk factor for a weak or null HR.

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“…In addition, the response to COVID-19 vaccination is another important challenge in immunosuppressed patients. It is found that discontinuation or dose reduction of MMF optimizes the COVID-19 vaccination response in LT patients[ 135 , 136 ]. Moreover, it is necessary to consider booster shots in immunosuppressed patients who do not demonstrate the appropriate response to vaccinations[ 137 ].…”

Section: Outcome Management and Considerations In Special Populationsmentioning

confidence: 99%

COVID-19 and liver injury: Pathophysiology, risk factors, outcome and management in special populations

Roshanshad¹,

Roshanshad²,

Fereidooni³

et al. 2023

World J Hepatol

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The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 is an ongoing health concern. In addition to affecting the respiratory system, COVID-19 can potentially damage other systems in the body, leading to extra-pulmonary manifestations. Hepatic manifestations are among the common consequences of COVID-19. Although the precise mechanism of liver injury is still questionable, several mechanisms have been hypothesized, including direct viral effect, cytokine storm, hypoxic-ischemic injury, hypoxia-reperfusion injury, ferroptosis, and hepatotoxic medications. Risk factors of COVID-19-induced liver injury include severe COVID-19 infection, male gender, advanced age, obesity, and underlying diseases. The presentations of liver involvement comprise abnormalities in liver enzymes and radiologic findings, which can be utilized to predict the prognosis. Increased gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase levels with hypoalbuminemia can indicate severe liver injury and anticipate the need for intensive care units’ hospitalization. In imaging, a lower liver-to-spleen ratio and liver computed tomography attenuation may indicate a more severe illness. Furthermore, chronic liver disease patients are at a higher risk for severe disease and death from COVID-19. Nonalcoholic fatty liver disease had the highest risk of advanced COVID-19 disease and death, followed by metabolic-associated fatty liver disease and cirrhosis. In addition to COVID-19-induced liver injury, the pandemic has also altered the epidemiology and pattern of some hepatic diseases, such as alcoholic liver disease and hepatitis B. Therefore, it warrants special vigilance and awareness by healthcare professionals to screen and treat COVID-19-associated liver injury accordingly.

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Mycophenolate mofetil discontinuation increases severe acute respiratory syndrome coronavirus 2 vaccine response in nonresponder liver transplantation recipients: A proof of concept

Cited by 6 publications

References 6 publications

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients

Durability of Immune Response after Application of a Third Dose of SARS-CoV-2 Vaccination in Liver Transplant Recipients

Evaluation of Humoral Response following SARS-CoV-2 mRNA-Based Vaccination in Liver Transplant Recipients Receiving Tailored Immunosuppressive Therapy

COVID-19 and liver injury: Pathophysiology, risk factors, outcome and management in special populations

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