Liver and Bile
J Hepatol. 2024;80(1):109–23
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 1–3 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 interferon γ 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.