Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant
Authors: Mehta Gautam , Riva Antonio , Ballester Maria Pilar , Uson Eva , Pujadas Montserrat , Carvalho-Gomes Ângela , Sahuco Ivan , Bono Ariadna , D’Amico Federico , Viganò Raffaela , Diago Elena , Lanseros Beatriz Tormo , Inglese Elvira , Vazquez Dani Martinez , Sharma Rajni , Tsou Hio Lam Phoebe , Harris Nicola , Broekhoven Annelotte , Kikkert Marjolein , Morales Shessy P. Torres , Myeni Sebenzile K. , Riveiro-Barciela Mar , Palom Adriana , Zeni Nicola , Brocca Alessandra , Cussigh Annarosa , Cmet Sara , Escudero-García Desamparados , Stocco Matteo , Natola Leonardo Antonio , Ieluzzi Donatella , Paon Veronica , Sangiovanni Angelo , Farina Elisa , di Benedetto Clara , Sánchez-Torrijos Yolanda , Lucena-Varela Ana , Román Eva , Sánchez Elisabet , Sánchez-Aldehuelo Rubén , López-Cardona Julia , Canas-Perez Itzel , Eastgate Christine , Jeyanesan Dhaarica , Morocho Alejandro Esquivel , Di Cola Simone , Lapenna Lucia , Zaccherini Giacomo , Bongiovanni Deborah , Zanaga Paola , Sayaf Katia , Hossain Sabir , Crespo Javier , Robles-Díaz Mercedes , Madejón Antonio , Degroote Helena , Fernández Javier , Korenjak Marko , Verhelst Xavier , García-Samaniego Javier , Andrade Raúl J. , Iruzubieta Paula , Wright Gavin , Caraceni Paolo , Merli Manuela , Patel Vishal C , Gander Amir , Albillos Agustín , Soriano Germán , Donato Maria Francesca , Sacerdoti David , Toniutto Pierluigi , Buti Maria , Duvoux Christophe , Grossi Paolo Antonio , Berg Thomas , Polak Wojciech G. , Puoti Massimo , Bosch-Comas Anna , Belli Luca , Burra Patrizia , Russo Francesco Paolo , Coenraad Minneke , Calleja José Luis , Perricone Giovanni , Berenguer Marina , Claria Joan , Moreau Richard , Arroyo Vicente , Angeli Paolo , Sánchez Cristina , Ampuero Javier , Piano Salvatore , Chokshi Shilpa , Jalan Rajiv ,   on behalf of the COBALT Consortium
Published: October 2023

Background:
Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection.

Methods:
COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4–10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected.

Results:
After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level.

Conclusions:
LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.