Liver and Bile

J Hepatol. 2024;80(1):109–23

Murray SM, Pose E, Wittner M, Londoño MC, Schaub G, Cook J, Dimitriadis S, Meacham G, Irwin S, Lim Z, Duengelhoef P, Sterneck M, Lohse AW, Perez V, Trivedi P, Bhandal K, Mullish BH, Manousou P, Provine NM, Avitabile E, Carroll M, Tipton T, Healy S, Burra P, Klenerman P, Dunachie S, Kronsteiner B, Maciola AK, Pasqual G, Hernandez-Gea V, Garcia-Pagan JC, Lampertico P, Iavarone M, Gines P, Lütgehetmann M, Schulze Zur Wiesch J, Russo FP, Barnes E, Marjot T; OCTAVE Collaborative Group; PITCH study; EASL supported COVID-Hep vaccine network

Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Background and aims: Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after 1 to 3 vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes.
Methods: A total of 849 participants (355 with cirrhosis, 74 with autoimmune hepatitis [AIH], 36 with vascular liver disease [VLD], 257 liver transplant recipients [LTRs] and 127 healthy controls [HCs]) were recruited from 4 countries. Standardized immune assays were performed pre and post 3 vaccine doses (V1–3).
Results: In the total cohort, there were incremental increases in antibody titers after each vaccine dose (p < 0.0001). Factors associated with reduced antibody responses were age and LT, whereas heterologous vaccination, prior COVID-19 and mRNA platforms were associated with greater responses. Although antibody titers decreased between post-V2 and pre-V3 (p = 0.012), patients with AIH, VLD, and cirrhosis had equivalent antibody responses to HCs post-V3. LTRs had lower and more heterogenous antibody titers than other groups, including post-V3 where 9% had no detectable antibodies; this was heavily influenced by intensity of immunosuppression. Vaccination increased T-cell IFNγ responses in all groups except LTRs. Patients with liver disease had lower functional antibody responses against 9 Omicron subvariants and reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type. 122 cases of breakthrough COVID-19 were reported of which 5 of 122 (4%) were severe. Of the severe cases, 4 of 5 (80%) occurred in LTRs and 2 of 5 (40%) had no serological response post-V2.

Conclusion: After 3 COVID-19 vaccines, patients with liver disease generally develop robust antibody and T-cell responses to vaccination and have mild COVID-19. However, liver transplant recipients have sustained no/low antibody titers and appear most vulnerable to severe disease.

DOI: 10.1016/j.jhep.2023.10.009