Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease

Abstract

The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among CLD patients of different etiologies and disease stages. 357 patients were recruited in clinical centers from 6 European countries. 132 healthy volunteers served as controls. Serum IgG, IgM (nM) and neutralizing antibodies (NAb; %) against the Wuhan-Hu-1, B.1.617 and B.1.1.529 SARS-CoV-2 spike proteins were determined prior to vaccination (T0), 14 days (T2) and 6 months (T3) after second dose vaccination. Patients fulfilling inclusion criteria at T2 (n=212) were stratified into "low" or "high" responders according to IgG levels. Infection rates and severity were collected throughout the study. Wuhan-Hu-1 IgG, IgM and neutralization levels significantly increased from T0 to T2 in patients vaccinated with either BNT162b2 (70.3%), mRNA-1273 (18.9%) or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted "low" humoral response, while viral hepatitis and antiviral therapy predicted "high" humoral response. Comparing with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, CLD patients presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-COV-2 infection rates or vaccine efficacy. Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease etiology. The type of vaccine leads to different antibody responses, that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a "lower" humoral response, while viral hepatitis etiology and prior antiviral therapy predict a "higher" humoral response. This differential response appears not to associate with SARS-COV-2 infection incidence or vaccine efficacy. Still, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritized for receiving booster doses and/or recently approved adapted vaccines.