Serological Responses to COVID-19 Vaccines Lower Among Patients with Chronic Liver Disease and Cirrhosis


Cirrhosis, older age, and vaccine type were among factors associated with lower antibody responses to COVID-19 vaccines in patients with chronic liver disease, new research shows.

Patients with chronic liver disease and cirrhosis had lower responsiveness to COVID-19 vaccines, but vaccine efficacy wasn’t affected, a recent study found.

The study, published in JHEP Reports, included 357 patients with chronic liver disease from six European countries and 132 healthy volunteers as controls. Investigators examined levels of serum IgG, IgM and neutralizing antibodies against spike proteins from three SARS-CoV-2 strains, Wuhan-Hu-1, B1617 and B11529.

“While several studies have suggested that patients with chronic liver disease (CLD) exhibit sub-optimal immune responses to COVID-19 vaccination, long-term responses of patients receiving two-dose mRNA vaccines, prior to receiving the third/boost dose, were largely unknown,” Rui Castro, PhD, of the Research Institute for Medicines, Faculty of Pharmacy at the University of Lisbon, told Contagion. “Our study showed that cirrhosis, older age, and type of vaccine predict lower antibody titers shortly after vaccination; and that humoral immunity is lower for SARS-CoV-2 variants, decreasing even more at 6-months following 2-dose vaccination. Noteworthy, no major clinical or immune IgG parameters associated with SARS-COV-2 infection rates or vaccine efficacy.”

Patients received two doses of Oxford-AstraZeneca, Pfizer-BioNTech or Moderna COVID-19 vaccines. More than 96% of patients responded to the vaccines, with immune responses increasing at two weeks and decreasing after six months.

Along with cirrhosis, age and vaccine type also were associated with lower IgG responses. Viral hepatitis and prior antiviral therapy were associated with higher immune responses. Immune responses were lower for Delta and Omicron variants.

Immune responses were highest among those who took the Moderna vaccine, followed by Pfizer and then AstraZeneca.

“We were surprised by two main findings; namely, that viral hepatitis and antiviral therapy stood as independent predictors of higher humoral immune responses—which warrants further studies—and that the distinct levels of antibodies induced by the distinct vaccine types, or associated with distinct disease etiology or severity, appear not to translate into lower vaccine efficacy (COVID-19 infection), at least within the first six months following two-dose vaccination,” Castro said.

Among those who took the AstraZeneca vaccine 8.6% had high immune responses (above the median 418.95 nM), compared with 51.7% for took the Pfizer vaccine and 67.5% for Moderna.

Compared with the Wuhan strain, IgG levels decreased against the Delta and Omicron variants.

“Although additional studies should ideally be performed, I think this message can already be communicated to patients. That is, that different two-dose mRNA COVID-19 vaccines are effective in a diverse group of patients with CLD,” Castro said. “This will help to boost confidence in the vaccination plans put in place by different governments. Notwithstanding, our results also highlight the need for patients with CLD, particularly those older and with cirrhosis, to receive booster shots. Ideally, patients should be prioritized for adapted vaccines against recent Omicron variants.”

Evaluation of IgG antibodies at two weeks found increased immune response among patients with viral hepatitis (odds ratio 2.34, 95% confidence interval 1.35-4.07) and antiviral therapy (OR 4.70, 95% CI 1.69-13.05).

Lower immune response was seen among patients with older age (OR 0.95, 95% CI 0.92-0.98), metabolic related fatty liver disease (OR 0.41, 95% CI 0.24-0.72) and metabolic drugs (OR 0.46, 95% CI 0.26-0.82) were associated with lower immune response.

A lower IgG response also was seen with the presence of F3-F4 fibrosis (OR 0.28, 95% CI 0.15-0.51) and cirrhosis (OR 0.28, 95% CI 0.15-0.50).

“Patients with chronic liver disease (CLD), particularly those with cirrhosis, are at higher risk of developing more severe COVID-19 and display higher mortality rates, compared to non-CLD patients,” Castro said. “As such, studies on vaccine efficacy in this vulnerable population are particularly relevant. It remains important to evaluate the overall (humoral and cellular) immune response of patients with CLD to recent Omicron strains and to adapted vaccines; and to compare it with that of healthy individuals. We are also particularly interested in further elucidating how viral hepatitis and antiviral therapy affect vaccine efficacy.”

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