Original Article
Pancreas, Biliary Tract, and Liver
SARS-CoV2-specific Humoral and T-cell Immune Response After Second Vaccination in Liver Cirrhosis and Transplant Patients

https://doi.org/10.1016/j.cgh.2021.09.003Get rights and content

Background & Aims

Detailed information on the immune response after second vaccination of cirrhotic patients and liver transplant (LT) recipients against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is largely missing. We aimed at comparing the vaccine-induced humoral and T-cell responses of these vulnerable patient groups.

Methods

In this prospective cohort study, anti-SARS-CoV-2 spike-protein titers were determined using the DiaSorin LIAISON (anti-S trimer) and Roche Elecsys (anti-S RBD) immunoassays in 194 patients (141 LT, 53 cirrhosis Child-Pugh A-C) and 56 healthy controls before and 10 to 84 days after second vaccination. The spike-specific T-cell response was assessed using an interferon-gamma release assay (EUROIMMUN). A logistic regression analysis was performed to identify predictors of low response.

Results

After the second vaccination, seroconversion was achieved in 63% of LT recipients and 100% of cirrhotic patients and controls using the anti-S trimer assay. Median anti-SARS-CoV-2 titers of responding LT recipients were lower compared with cirrhotic patients and controls (P < .001). Spike-specific T-cell response rates were 36.6%, 65.4%, and 100% in LT, cirrhosis, and controls, respectively. Altogether, 28% of LT recipients did neither develop a humoral nor a T-cell response after second vaccination. In LT recipients, significant predictors of absent or low humoral response were age >65 years (odds ratio [OR], 4.57; 95% confidence interval [CI], 1.48-14.05) and arterial hypertension (OR, 2.50; 95% CI, 1.10-5.68), whereas vaccination failure was less likely with calcineurin inhibitor monotherapy than with other immunosuppressive regimens (OR, 0.36; 95% CI, 0.13-0.99).

Conclusion

Routine serological testing of the vaccination response and a third vaccination in patients with low or absent response seem advisable. These vulnerable cohorts need further research on the effects of heterologous vaccination and intermittent reduction of immunosuppression before booster vaccinations.

Keywords

Immunosuppression
Liver Cirrhosis
Liver Transplant Recipients
SARS-CoV-2 Vaccination

Abbreviations used in this paper

Anti-S RBD
anti-SARS-CoV-2 antibodies in Roche Elecsys immunoassay
anti-S trimer
anti-SARS-CoV-2 antibodies in DiaSorin LIAISON immunoassay
BAU
binding antibody units
CI
confidence interval
CNI
calcineurin inhibitor
COVID-19
Coronavirus disease 2019
eGFR
estimated glomerular filtration rate
IGRA
interferon gamma release assay
IFN-γ
interferon-gamma
IQR
interquartile range
LC
liver cirrhosis
LT
liver transplant
MMF
mycophenolate mofetil
mTORi
mammalian target of rapamycin inhibitors
OR
odds ratio
RBD
receptor binding domain
SARS-CoV-2
severe acute respiratory syndrome coronavirus type 2
SD
standard deviation
SOT
solid-organ transplantation
TIPS
transjugular intrahepatic portosystemic stent-shunt

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Conflicts of interest The authors disclose no conflicts.

Funding Friedrich Haag and Julian Schulze zur Wiesch report research funding from SFB1328, project A12; Golda Meline Schaub was supported by a DZIF MD Stipend through the DZIF academy. Anahita Fahti, Marylyn Martina Addo, and Leonie Mayer report funding from the DZIF TTU 01709. No further funding was used for the research reported.

a

Authors share co-first authorship.

b

Authors share co-senior authorship.

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