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.
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.
- 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’.
type of tumour affecting the lymph nodes.
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
Seventy-four per cent had compensated cirrhosis and the median
MELD score was 8. Fifty-six per cent had oesophogastric varices and 31% had
Two-thirds of people with cirrhosis received the Pfizer vaccine
compared to 76% of the control group; the remainder received the Moderna
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
(0.4-12,500) U/ml vs 1,520 (259-12,500) U/ml, p=0.048).
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.
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.
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
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.