Liver and Bile

J Hepatol. 2022;77(1):152–62

Toniutto P, Falleti E, Cmet S, Cussigh A, Veneto L, Bitetto D, Fornasiere E, Fumolo E, Fabris C, Sartor A, Peressutti R, Curcio F, Regattin L, Grillone L

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients

Background and aims: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. The authors aimed to assess the long-term antibody response of the BNT162b2 vaccine in LT recipients compared to controls.
Methods: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein immunoglobulin (Ig)G (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose.
Results: 143 LT recipients and 58 controls were enrolled. At baseline, 131 of 143 LT recipients (91.6%) tested anti-N-negative (COVID-19-naive), and 12 of 143 (8.4%) tested positive (COVID-19-recovered) compared to negative controls. Among COVID-19-naive, 22.1% were anti-RBD-positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p < 0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 IU/ml) in COVID-19-naive than in controls (852 IU/ml; p < 0.0001). A higher daily dose of mycophenolate mofetil (MMF; p < 0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD-negativity at 6 months. All COVID-19-recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9400 IU/ml, 11,925 IU/ml, 13,305 IU/ml, and 10,095 IU/ml) or not taking MMF (13,950 IU/ml, 9575 IU/ml, 3500 IU/ml, 2835 IU/ml; p = n.s.) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively.

Conclusions: In COVID-19-naive liver transplant recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. Mycophenolate mofetil was the main determinant of vaccination failure in SARS-CoV-2-naive patients.

Prof. Dr. P. Toniutto, Department of Specialized Medicine, Hepatology and Liver Transplantation Unit, Udine University Hospital, Udine, Italy,

DOI: 10.1016/j.jhep.2022.02.015

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