Cirrhotic patients are in urgent need of a third SARS-COV-2 vaccine

Cirrhotic patients had insufficient T cell reactivity after 2 mRNA vaccine doses. But a booster and a natural infection led to higher antibody levels in this group.

T cell-derived interferon-gamma levels measured

Patients with liver cirrhosis have an elevated risk for adverse outcomes after a COVID-19 infection and have a markedly elevated COVID-19-related mortality1. How well can these high-risk patients be protected by vaccination? Dr Samer Al-Dury (Sahlgrenksa University Hospital, Sweden) and his team determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 cirrhotic patients (of variable aetiologies) and 39 healthy controls after 2 and 3 doses of an mRNA COVID-19 vaccine.

SARS-CoV-2-specific T cell reactivity was measured by induced levels of T cell-derived interferon-gamma (IFN-gamma) before and after the first and second vaccination with an mRNA vaccine (by Pfizer-BionNTech or Moderna). Moreover, serum IgG antibodies against the receptor-binding domain (RBD) of the spike protein were quantified by immunoassays after the first, second, and third dose of the vaccine. 

T cell reactivity against S1 was significantly reduced in cirrhotic patients compared with healthy controls after the first and second dose of the vaccine (P<0.001 for each comparison). Most (68%) patients lacked detectable S1-specific T cell reactivity after the first vaccination compared with 19% in controls (P=0.003) and 36% remained without detectable reactivity after the second dose versus 6% in the controls (P =0.009).

Protection achieved by reiterated vaccination or hybrid immunity

The lack of T cell reactivity was mirrored by lower levels of anti-RBD-S1 IgG after the first (P<0.001) and second (P<0.05 vs controls) vaccination. Impaired T cell reactivity in cirrhosis remained after correction for potential confounders and was particularly pronounced in patients with advanced cirrhosis.

Anti-RBD-S1 IgG levels, however, were increased significantly after the third compared with the second dose. Patients who were vaccinated and had a naturally acquired COVDI-19 infection (hybrid immunity) achieved the best T cell reactivity, with significantly higher antibody levels compared with antibody levels achieved through 3 doses of vaccination alone. 

Thus, in cirrhotic patients, protective immunity is achievable by reiterated COVID-19 vaccination and by hybrid immunity. 

  1. Nagarajan R, et al. Prev Chronic Dis 2022;19:210228.
  2. Al-Dury S, et al. Evaluation of the immune response against SARS-COV-2 after two and three doses of mRNA vaccination in patients with liver cirrhosis. OP106, UEG Week 2022, Vienna, Austria, 8–11 October.