People with liver cirrhosis have weaker responses to the Pfizer and Moderna SARS-CoV-2 vaccines

Keith Alcorn
Published:
16 November 2021
Image by Marco Verch. Creative Commons licence.

People with cirrhosis of the liver had delayed and suboptimal responses to the Pfizer or Moderna SARS-CoV-2 vaccines compared to healthy adults, an Italian study has found. People with decompensated cirrhosis had significantly weaker responses compared to those with compensated cirrhosis, Professor Massimo Iavorone of Ca’ Grande Ospedale Policlinico, Milan, told The Liver Meeting in a late-breaker session on Monday.

People with cirrhosis have suboptimal responses to pneumococcus and flu vaccines. There is limited information about response to SARS-CoV-2 vaccines in people with cirrhosis as clinical trials of the vaccines included few people with chronic liver disease.

Israeli researchers reported that people with non-alcoholic fatty liver disease and more advanced fibrosis had weaker responses to the Pfizer SARS-CoV-2 vaccine. It is unclear if vaccine responses are similarly impaired in people with cirrhosis due to other causes or if vaccine responses are weaker in people with decompensated cirrhosis.

Glossary

compensated cirrhosis

The earlier stage of cirrhosis, during which the liver is damaged but still able to perform most of its functions. See also ‘cirrhosis’ and ‘decompensated cirrhosis’.

decompensated cirrhosis

The later stage of cirrhosis, during which the liver cannot perform some vital functions and complications occur. See also ‘cirrhosis’ and ‘compensated cirrhosis’.

lymphoma

A type of tumour affecting the lymph nodes.

varices

Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.

To investigate these questions, Italian researchers designed a prospective observational study to measure vaccine responses in all patients with cirrhosis under care at Ca’ Grande Ospedale Policlinico who received the Pfizer or Moderna SARS-CoV-2 mRNA vaccines.

The study measured levels of antibodies to the SARS-CoV-2 spike protein 21 days after first vaccination, 21 days after the second dose and 133 days after the second dose. The study also measured levels of SARS-CoV-2 spike antigen-specific T-cells at the same intervals.

The study recruited 182 people with cirrhosis and 38 healthy controls. People with cirrhosis had a median age of 61 years, 75% were male and 92% were White. Forty-five per cent had cirrhosis associated with viral hepatitis, 14% had cirrhosis associated with alcoholic liver disease, 8% cirrhosis due to metabolic disease and 33% had cirrhosis with multiple or other causes.

Seventy-four per cent had compensated cirrhosis and the median MELD score was 8. Fifty-six per cent had oesophogastric varices and 31% had hepatocellular carcinoma.

Two-thirds of people with cirrhosis received the Pfizer vaccine compared to 76% of the control group; the remainder received the Moderna vaccine.

Fifteen per cent of people with cirrhosis and 31% of the control group had a previous COVID-19 illness, so results were analysed according to prior COVID-19 status.

Twenty-one days after the first vaccine dose, people with cirrhosis without prior COVID-19 had significantly lower median antibody titres than controls without prior COVID-19 (13.9 (0.4-12,500) U/ml vs 43.1 (0.4-345) U/ml, p=0.001).

Antibody titres remained significantly lower in people with cirrhosis without prior COVID-19 compared to the control group after the second dose (998.5 (0.4-12,500) U/ml vs 1,520 (259-12,500) U/ml, p=0.048).

Among people with a prior history of COVID-19, median antibody titres did not differ significantly between people with cirrhosis and controls (7,500 (273-12,500) U/ml vs 12,500 (8,952 vs 12,500 U/ml) after the first dose.

After the second dose, antibody levels were significantly lower in people with cirrhosis without a history of COVID-19 who had hepatocellular carcinoma (p=0.012), people with decompensated cirrhosis (Child-Pugh B/C stage) (p=0.028) and people who received the Pfizer vaccine (p=0.0002). In a multivariable analysis, lower antibody titres after the second dose were associated with active HCC or immunosuppression (recent steroid treatment, lymphoma or HIV), while higher antibody titres were associated with receipt of the Moderna vaccine or a high antibody titre after the first vaccine dose.

A preliminary analysis of cellular immune responses after the first and second doses showed weaker T-cell responses in people with cirrhosis and little increase in IL-2 or interferon-gamma levels up to 60 days after the first vaccine dose.

Post-vaccination follow-up in 155 patients with cirrhosis 133 days after the second dose showed that four people without a previous history of COVID-19 had acquired SARS-CoV-2. All had experienced asymptomatic infections.

Reference

Iavorone M et al. Delayed and suboptimal response to two doses of SARS-CoV-2 messenger RNA vaccine in European patients with compensated and decompensated cirrhosis of different aetiologies: interim analysis. The Liver Meeting, late breaker abstract, 2021.

Full image credit: A man is getting an injection with a syringe at hospital. Image by Marco Verch Professional Photographer. Available at https://foto.wuestenigel.com/a-man-is-getting-an-injection-with-a-syringe-at-hospital/ under a Creative Commons licence CC BY 2.0.