SARS-CoV-2 vaccination in patients with liver disease: responding to the next big question

Abstract

Involvement of patients with liver disease in phase 3 SARS-CoV-2 vaccine trials and key outstanding questions Chronic liver disease and cirrhosisTrial inclusion and exclusion criteria • Pfizer/BioNTech: "liver disease" included but not defined • Moderna: "liver disease" included but not defined • Oxford/AstraZeneca: "liver disease" excluded (except Gilbert syndrome), "alcohol and drug dependency…injecting drug abuse in the 5 years preceding enrolment" excluded Key outstanding questions • Magnitude and duration of vaccine response • Disease severity in predicting vaccine response • Differential efficacies of single doses or additional booster doses • Risk of liver injury unknown Liver transplantation Trial inclusion and exclusion criteria • Pfizer/BioNTech: "Individuals who receive treatment with immunosuppressive therapy" excluded • Moderna: "Immunosuppressive or immunodeficient state" or "systemic immunosuppressants or immune-modifying drugs for >14 days" excluded • Oxford/AstraZeneca: "Any confirmed or suspected immunosuppressive or immunodeficient state" excluded Key outstanding questions • Magnitude and duration of vaccine response • Durability of response post-transplantation; optimal timing of prime and boost vaccination in relation to transplantation • Interactions with specific immunosuppression regimens • Differential efficacies of single doses or additional booster doses • Risk of liver injury unknown Immunosuppressed autoimmune liver disease (eg, autoimmune hepatitis) Trial inclusion and exclusion criteria • Pfizer/BioNTech: "Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention" excluded • Moderna: "Immunosuppressive or immunodeficient state" or "systemic immunosuppressants or immune-modifying drugs for >14 days" excluded • Oxford/AstraZeneca: "Any autoimmune conditions" excluded Key outstanding questions • Magnitude and duration of vaccine response

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

“…Of note, a subgroup of patients in the UK received a lower initial vaccine dose followed by booster vaccination with the standard dose and showed 90% efficacy, whereas the standard regimen resulted in vaccine efficacy of only 62%. 44 Despite the high number of study participants, only few patients with mild to moderate liver disease were included in the trials and patients with immunosuppressive conditions were excluded (reviewed in 18 ). However, in real life, a substantial number of individuals have already been vaccinated worldwide, including patients with liver disease; thus, data on safety and effectiveness are expected to be available soon.…”

“…As a general rule and based on the available experience on vaccination of organ transplant patients against other pathogens, it is advised that liver transplant candidates be vaccinated prior to transplantation whenever applicable. In addition, it is important to note that phase III trials of current vaccine candidates have excluded organ transplant recipients and patients receiving immunosuppressive drugs (reviewed in 18 ). Therefore, further clinical trials should include such patient populations.…”

“…[15][16][17] As a final note, there is no confirmed information yet on the tolerability, immunogenicity and safety of novel COVID-19 vaccines in patients with CLD, including patients with hepatobiliary cancer. 18 Efficacy and safety of vaccines in solid organ transplant recipients Solid organ transplant (SOT) recipients are at an increased risk of infection because of the immunosuppression required to prevent graft rejection. In addition, infections can be more severe in transplant recipients than in immunocompetent individuals.…”

“…31 While data are available for most of the recommended vaccines in SOT (Table 2), there is so far no confirmed information on the tolerability, reactogenicity, immunogenicity and overall safety of COVID-19 vaccines in SOT patients given the design of the phase III trials. 18…”

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study

“… [3] , [4] , [5] Despite the large number of clinical trials of COVID-19 vaccines, only a few participants with pre-existing liver diseases were included. 1 , 6 Concerns have been raised recently about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD), 1 , 6 , 7 who may be uniquely susceptible to COVID-19 infection and disease progression. [8] , [9] , [10] The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in patients with NAFLD in a large Chinese cohort.…”