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Worse Antibody and Cellular Response
to SARS-CoV-2 Vax With Cirrhosis
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AASLD, The Liver Meeting, November 12-15, 2021
Mark Mascolini
Antibody- and cell-mediated responses to mRNA SARS-CoV-2 vaccines were feebler and delayed in people with cirrhosis compared with healthy noncirrhotics in a prospective comparison conducted by researchers at Milan's Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico [1]. The study did not find vaccine-related serious adverse events in people with cirrhosis.
COVID-fighting vaccines exploiting SARS-CoV-2 messenger RNA (mRNA), like the Pfizer-BioNTech and Moderna vaccines, have up to 95% efficacy in preventing serious COVID-19 in the general population. Because little is known about how well these vaccines generate immune responses in people with cirrhosis, researchers from Milan's Fondazione IRCCS and collaborators at other centers performed a prospective comparison of antibody- and cell-mediated responses to mRNA vaccines in people with cirrhosis and healthy controls.
The investigators measured SARS-CoV-2 IgG antibodies targeting the viral spike protein (anti-S antibody) before people got vaccinated, 21 days after the first dose, and 21 days after the second dose. They tested 60-year-old and older healthy (noncirrhotic) people at the same points. The researchers gauged cellular immune response to the vaccines by measuring interferon-gamma (IFN-g) and interleukin 2 (IL-2) in 13 people with cirrhosis, 2 of whom had COVID-19 before vaccination, and compared those responses to healthy controls.
The analysis focused on 182 people with cirrhosis averaging 61 years in age, 75% of them men. Most of these people, 59%, had virus-related cirrhosis, 74% had Child-Pugh A (well-compensated) cirrhosis, 31% had hepatocellular carcinoma (HCC), 15% were waiting for a liver transplant, and 16% already had SARS-CoV-2 infection. Of the 38 noncirrhotic controls studied, 12 (31%) had been exposed to SARS-CoV-2.
After the first mRNA vaccine dose, anti-S antibody levels lay significantly lower in people with cirrhosis than in healthy controls: 22.8 (0.4-12,500) U/L versus 84.75 (0.4-12,500) U/mL (P = 0.0001). The antibody response was even lower in the cirrhosis subgroup without previous SARS-CoV-2-13.9 (0.4-12,500) U/L-than in controls without earlier COVID-19-43.1 (0.4-345) U/mL (P = 0.001).
The mRNA vaccine response pattern in people with versus without cirrhosis did not improve after the second dose. In people without prior SARS-CoV-2 infection, anti-S antibody level remained significantly worse in people with cirrhosis than in healthy controls: 1034 (0.4-12,500) U/mL versus 1520 (259-12,500) U/mL (P = 0.05).
After the second dose in people without earlier SARS-CoV-2 infection, those with decompensated cirrhosis, HCC, and undetectable anti-S antibody after the first dose had significantly lower anti-S antibody levels after the second dose:
- Decompensated cirrhosis: 637 (0.4-12,500) versus 1377 (0.4-12,500) U/mL, P = 0.01
- HCC: 1116 (0.4-7500) versus 1810 (0.4-12,500) U/mL, P = 0.02
- Undetectable antibody after first dose: 469 (0.4-4,780) versus 3908 (91.7-12,500) U/mL, P < 0.0001
In people with cirrhosis, vaccine-evoked cellular immunity against SARS-CoV-2 lagged cellular responses in healthy controls, as indicated by significantly lower IFN-g and IL-2 levels in the cirrhosis group.
"In patients with cirrhosis, specifically in those with advanced disease," the researchers concluded, "response to SARS-CoV-2 vaccines was delayed and suboptimal compared to the general population."
Reference
1. Iavarone 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. AASLD, The Liver Meeting, November 12-15, 2021. Abstract L011.
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