Vaccines protect liver disease patients against severe COVID-19

Patients with liver disease develop antibodies and T-cell responses following three shots of COVID-19 vaccines, while those who have been infected with SARS-CoV-2 develop mild symptoms only, reports a recent study.

However, liver transplant recipients (LTRs) show no or low antibody titres and seem to be in danger of severe COVID-19.

“[W]e demonstrate that the three most widely available vaccine platforms are immunogenic and appear to protect against severe COVID-19 in a diverse group of patients with a variety of underlying liver conditions,” the investigators said. “Even patients with advanced cirrhosis mount robust immune responses after two and three vaccine doses irrespective of vaccine type.”

Of the 849 participants recruited from four countries, 355 had cirrhosis, 74 had autoimmune hepatitis (AIH), 36 had vascular liver disease (VLD), 257 were LTRs, and 127 were healthy controls. The investigators conducted standardized immune assays before and after three vaccine doses.

Antibody titres increased incrementally following each vaccine dose (p<0.0001). Heterologous vaccination, prior COVID-19, and mRNA platforms contributed to greater antibody responses, while age and LT were associated with reduced antibody responses. [J Hepatol 2024;80:109-123]

“In our cohort, use of the mRNA platform was associated with greater antibody titres compared to ChAdOx1 which is in line with other datasets in healthy and immunosuppressed cohorts,” the investigators said. [Nat Commun 2022;13:4710; npj Vaccin 2021;6:74]

“In addition, as observed in healthy populations, heterologous first and second vaccination was associated with [a] fivefold increase in … antibody responses [after the second dose] compared to homologous vaccine delivery, suggesting that this approach should also be considered in liver cohorts,” they noted. [The Lancet 2022;399:36-49]

Antibody titres decreased between the second and third vaccination doses (p=0.012), but patients with AIH, VLD, and cirrhosis showed antibody responses equal to that of healthy controls after the third dose.

Transplant recipients

On the other hand, LTRs exhibited lower and more heterogenous antibody titres than other groups, including 9 percent with no detectable antibodies following the third vaccination dose. The intensity of immunosuppression strongly contributed to this condition. Additionally, all groups showed increased T-cell IFNγ responses, except LTRs.

Notably, patients with liver disease displayed lower functional antibody responses against nine Omicron subvariants and had reduced T-cell responses to Omicron BA.1-specific peptides compared to wild-type.

There were 122 breakthrough cases of COVID-19 reported, of which five (4 percent) were severe. Four of the five severe cases (80 percent) were LTRs, while two (40 percent) had no serological response after receiving the second dose.

“We recommend that LTRs should be vigilantly monitored for the development of severe COVID-19 if infected and prioritized for repeated vaccination, prophylactic antiviral agents, and enrolment into trials exploring the role of immunosuppressive dose modification and alternative vaccine strategies,” the investigators said.

“These insights may prove useful in the event of future viral infections which also require rapid vaccine development and delivery to patients with liver disease,” they noted.