COVID-19 vaccine protection is ‘lower and slower’ in people with cirrhosis

People with cirrhosis of the liver may take longer to achieve protection from SARS-CoV-2 and severe COVID-19 after vaccination, according to large studies in the United States and Chile, presented earlier this month at The Liver Meeting.

People with cirrhosis have weaker responses to many vaccines due to immune dysregulation and research presented at the conference showed that people with decompensated cirrhosis had especially weak responses to vaccination with the Pfizer or Moderna SARS-CoV-2 vaccines.

However, there is limited information about the impact of SARS-C0V-2 vaccination on the prevention of severe COVID-19 in people with cirrhosis, as people with chronic liver disease were excluded from registration studies of vaccines.

Two large studies reported on the clinical impact of vaccination in people with cirrhosis.

Binu V. John of University of Miami Miller School of Medicine presented the findings of an analysis of the Veterans Outcomes and Costs Associated with Liver disease (VOCAL) cohort, which tracks approximately 120,000 US military veterans with cirrhosis receiving care through the VA medical system.

The study findings were also published in the October edition of JAMA Internal Medicine.

The study investigated vaccine protection against infection and severe illness by tracking four outcomes: a positive SARS-CoV-2 PCR test 28 days after the first vaccine dose, a positive PCR result 7 days after the second vaccine dose, and hospitalisation or death due to COVID-19 28 days after the first dose and 7 days after the second dose.

The study matched recipients of the Pfizer or Moderna vaccines with controls by date of vaccination, age, sex, race, ethnicity, co-morbidities, alcoholic liver disease status and Child-Pugh score.

The published analysis included people with cirrhosis who received the Pfizer or Moderna vaccine up to 17 March 2021, with no previous history of COVID-19 or liver transplant. A total of 20,037 people were eligible for inclusion in the analysis and matched with an unvaccinated control with cirrhosis. (Of note, 34,184 people with cirrhosis remained unvaccinated by 17 March 2021, three months after vaccination began in the United States.)

Study participants were almost all male (97%), had a median age of 67 years, 60% were White, 23% Black, 43% had alcohol-related cirrhosis, 34% were overweight and 34% were obese. Over half (52%) had diabetes and 31% had three or more co-morbidities. Most had compensated cirrhosis (Child-Pugh Class A, 84%) and the median MELD score was 8.

There was no significant difference in SARS-CoV-2 infection up to 28 days after the first dose between vaccinated and unvaccinated participants, but after the first 28 days, receipt of a first dose of either vaccine was associated with a 64.8% reduction in infection. Seven days after the second vaccine dose, receipt of either vaccine was associated with a 78.6% reduction in the risk of infection.

Prior to 28 days after vaccination, the number of hospitalisations was similar in the vaccinated and unvaccinated groups (28 vs 29). Receipt of a first dose of vaccine was associated with a 100% reduction in the risk of hospitalisation or death due to COVID-19 from 28 days after vaccination, as was a second dose.

When the analysis was restricted to the 3142 people with decompensated cirrhosis, receipt of the first vaccine dose was associated with a 50.3% reduction in the risk of infection more than 28 days after vaccination and a 100% reduction in the risk of hospitalisation or death due to COVID-19. The investigators say that this result needs to be confirmed in other populations due to the low event rates for infections and hospitalisation (one infection in the vaccinated group and two in the control group after 28 days, and one hospitalisation in the control group).

In people with compensated cirrhosis, a first dose reduced the risk of infection after 28 days by 66.8%.

The study investigators point out that lack of protection against infection during the 28 days after the first dose contrasts with the higher efficacy seen in clinical trials of the Pfizer and Moderna vaccines. They suggest that people with cirrhosis may have impaired or delayed humoral immunity, underlining the importance of maintaining strict preventive measures against infection until the full vaccination course has been completed.

Chile has achieved one of the highest rates of SARS-CoV-2 vaccination in the world. By 3 October 2021, 81% of adults had received at least one dose of a vaccine and more than 70% were fully vaccinated, Dr Luis Antonio Díaz of Pontificia Universidad Católica De Chile School of Medicine told The Liver Meeting.

Dr Diaz reported on the incidence of hospitalisation for COVID-19 in Chile between 3 March and 30 May 2021 in people with laboratory-confirmed SARS-CoV-2 infection, reported to the national SARS-CoV-2 surveillance system. During this period 1,648,680 cases were reported, 84% confirmed by PCR test. Of these, 7.7% required hospitalisation. But in people with cirrhosis, who made up 0.1% of all reported cases, the hospitalisation rate was 49.2%.

When hospitalisation was analysed according to vaccination status, hospitalisation was 12.6% lower in people with cirrhosis more than two weeks after the second dose compared to the hospitalisation rate in unvaccinated people with cirrhosis (p<0.001). Vaccination was also associated with lower hospitalisation rates in people with chronic heart disease, hypertension, type 2 diabetes or asthma, although the effect was most pronounced in people with cirrhosis.