“Our group previously demonstrated that in patients with cirrhosis, the effectiveness associated with two doses of an mRNA vaccine was lower and slower compared to that seen in a healthy population,” explained lead investigator Binu V. John, MD, MPH, Division of Gastroenterology and Hepatology, Miami VA Medical System, and Division of Digestive Health and Liver Disease, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. “Patients with cirrhosis are particularly vulnerable to the impact of COVID-19, presenting higher hospitalization and mortality rates compared to those without liver disease. These findings inspired us to focus on the next question: What is the additional benefit of booster doses in cirrhosis, and particularly against the delta and omicron variants.”

Investigators performed a retrospective cohort study of patients with cirrhosis who received two or three doses of doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines at the Veterans Health Administration between December 18, 2020 and February 11, 2022, when the delta and omicron variants were active. Around 13,000 participants who received three doses of the vaccine were propensity-matched with 13,000 controls who had received two doses.

Patients who received three doses were evaluated for the development of COVID-19 and disease severity.

Results indicated that patients with cirrhosis should be encouraged to receive a third dose for effective protection because it appears to be highly effective against severe outcomes of COVID-19. The findings showed that the receipt of the third dose of either the BNT162b2 mRNA or the mRNA-1273 vaccines is associated with an 80% decrease in the development of COVID-19 and symptomatic COVID-19, and a 100% reduction in severe or critical COVID-19 and COVID-19 — related death, compared to participants with cirrhosis who received only 2 doses.

“This reduction associated with the third dose is significantly higher than that described in a healthy population and suggests that a third dose of the COVID-19 mRNA vaccine is able to overcome the vaccine hyporesponsiveness in cirrhosis,” noted Dr. John. “This study suggests that a third dose of an mRNA vaccine is able to offer significant protection against COVID-19, and particularly against severe disease. The vaccine was observed to be protective in both patients with compensated cirrhosis (where the liver function is relatively preserved and patients have no symptoms of liver disease), and decompensated cirrhosis (when liver disease is worse and associated with symptoms), but the magnitude of reduction was greater in patients with compensated cirrhosis. It adds to the growing body of evidence demonstrating the importance of COVID-19 vaccination in cirrhosis.”

The investigators noted that their findings were surprising. “We had anticipated that the third dose may offer greater protection compared to two doses. However, the magnitude of reduction was remarkable, and even greater than seen in the healthy population. Our results show that patients with cirrhosis should definitely receive the third vaccination dose, and potentially all boosters now recommended,” concluded Dr. John.

Cirrhosis of the liver is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. It is associated with decreased responsiveness to most vaccines, including against COVID-19.