Impact of SARS-CoV-2 vaccination in patients with vascular liver diseases: Observations from a VALDIG multicenter study

Abstract

Background & aims: Patients with vascular liver diseases (VLD) are at higher risk of both severe courses of COVID-19 disease and thromboembolic events. The impact of SARS-CoV-2 vaccination in patients with VLD has not been described and represents the aim of our study.

Methods: International, multicenter, prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation. In a subgroup of patients, the humoral and cellular responses to vaccination were also analyzed.

Results: A total of 898 patients from 14 European centers - part of the VALDIG network - were included, 872 (97.1%) patients received two vaccine doses (fully vaccinated), and 674 (75.1%) three doses. Of the total cohort, 151/898 had a COVID-19 infection prior to vaccination, of whom 9/151 (5.9%) were re-infected. Of the 747/898 patients who were not previously infected, 11.2% (84/747) were diagnosed with a COVID-19 infection during the study period. Two infected patients required intensive care unit admission and infection was fatal in two fully vaccinated patients. Adverse effects were reported in around 40% of patients, with local side effects being the most frequent. During the study period, 31 (3.5%) patients had thromboembolic events and 21 (2.3%) hepatic decompensations. No cases of vaccine-induced thrombocytopenia were reported. Vaccine immunogenicity was assessed in 36 patients; seroconversion reached 100% and IFNy T-cell responses significantly increased post two mRNA-1273 vaccine doses.

Conclusion: Patients with VLD seem to have a preserved immune response to SARS-CoV-2 vaccination, which appears to be safe and effective in preventing severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, though the contribution of vaccination as a cofactor in VLD remains to be elucidated.

Impact and implications: Patients with vascular liver disease (VLD) are at increased risk of both SARS-CoV-2 infection and severe COVID-19 disease. The potential risks associated with vaccination against this infection need thorough investigation. Our research enhances the understanding of the effects of COVID-19 vaccination in patients with VLD, highlighting its good tolerability. Moreover, patients with VLD appear to have a preserved immune response to SARS-CoV-2 vaccination, providing protection against severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, and no cases of vaccine-induced thrombocytopenia were reported.

Keywords: COVID-19 vaccine; Vascular liver disease; portal thrombosis.

Graphical abstract

Fig. 1

COVID-19 infection in the total cohort. Created in BioRender. Hernandez-gea, V. (2024) BioRender.com/ o45q212.

Fig. 2

Thromboembolic events after vaccination and during the follow-up period. Kaplan-Meier method. VLD, vascular liver disease.

Fig. 3

Serological and cellular responses to mRNA-1273 in SARS-COV-2 infection naïve patients with VLD. (A) Antibody response to SARS-COV-2 spike protein RBD assessed before first dose (Pre-V1), before second dose (Pre-V2), 28-days following second dose (Post-V2), before third dose (Pre-V3) and 28-days following third dose (Post-V3) (n = 30). (B) IFNy T cell responses to overlapping peptide pools covering Wuhan Hu-1 SARS-CoV-2 spike (S1+S2) (n = 23) and (C) IFNy T cell responses to overlapping peptide pools covering Omicron BA.1 at the post-V3 timepoint (n = 19). (D, E) the magnitude of anti-RBD Ig (D) and IFNy T cell responses to Wuhan Hu-1 SARS-COV-2 spike (E) at the post-v2 timepoint in individuals that did or did not report breakthrough COVID-19 infection after two doses of COVID-19 vaccine. Median and IQR shown. (A) Bars and lines represent min, max, IQR and median. Mann-Whitney U, Wilcoxon matched-pairs signed rank test or Kruskal-Wallis test were used. BCS, Budd-Chiari syndrome; NCPVT, non-cirrhotic non-tumoral portal vein thrombosis; PSVD, portal sinusoidal vascular disease; RBD, receptor binding domain; VLD, vascular liver disease.